КОНЪЮГАТ АНТИТЕЛО-ЛЕКАРСТВЕННОЕ СРЕДСТВО, СОДЕРЖАЩИЙ ГЕТЕРОЦИКЛИЧЕСКОЕ СОЕДИНЕНИЕ, ОБЛАДАЮЩЕЕ ЭФФЕКТОМ ИНДУКЦИИ ДЕГРАДАЦИИ МУТАНТНОГО БЕЛКА KRAS G12D

Abstract

Предложен конъюгат антитело-лекарственное средство для применения для лечения злокачественной опухоли, экспрессирующей мутантный KRAS G12D. Также предложен конъюгат лекарственное средство-линкер для применения в конъюгате антитело-лекарственное средство. Авторы настоящего изобретения осуществили конъюгацию гетероциклического соединения, соответствующего формуле (I), с антителом, например антителом против EGFR, с получением конъюгата антитело-лекарственное средство, способного доставлять соединение к злокачественной опухоли, например EGFR-экспрессирующей злокачественной опухоли. Более того, был выявлен конъюгат лекарственное средство-линкер для применения в конъюгате антитело-лекарственное средство или его соли. Конъюгат антитело-лекарственное средство ингибирует мутантный KRAS G12D путем индукции деградации мутантного белка KRAS G12D в злокачественной опухоли, например, EGFR-экспрессирующей злокачественной опухоли, и проявляет противоопухолевый эффект.

Description

Antibody-drug conjugate containing heterocyclic compound having G12D mutant KRAS proteolysis-inducing activity The present invention relates to a pharmaceutical composition, particularly an antibody-drug conjugate or a salt thereof containing a heterocyclic compound (hereinafter, the compound may be referred to as a drug) having the activity of inducing G12D mutant KRAS proteolysis. The present invention also relates to a drug-linker conjugate or a salt thereof for use in the antibody-drug conjugate or a salt thereof. RAS proteins are small guanosine triphosphate (GTP)-binding proteins of approximately 21 kDa, consisting of 188–189 amino acids. There are four major RAS proteins (KRAS (KRAS4A and KRAS4B), NRAS, and HRAS) produced by three genes: KRAS, NRAS, and HRAS. RAS proteins exist in active, GTP-bound forms and inactive, GDP-bound forms. RAS proteins are activated by the exchange of guanosine diphosphate (GDP) for GTP upon ligand stimulation of cell membrane receptors such as EGFR. Active RAS binds to 20 effector proteins, including RAF, PI3K, and RALGDS, and activates downstream signaling cascades. On the other hand, active RAS becomes inactive by converting GTP to GDP through its intrinsic GTP hydrolysis (GTPase) activity. This GTPase activity is enhanced by GTPase-activating proteins (GAPs). This indicates that RAS functions as an important "molecular switch" in intracellular signaling pathways such as EGFR, and plays an important role in processes such as cell growth, proliferation, and angiogenesis (Nature Rev. Cancer, 2011, 11, pp. 761-774; Nature Rev. Drug Discov., 2014, 13, pp. 828-851; Nature Rev. Drug Discov., 2016, 15, pp. 771-785). When RAS mutations result in amino acid substitutions, RAS becomes constitutively active due to impaired GTPase function and reduced response to GAPs, resulting in continuous downstream signaling. This excessive signaling leads to carcinogenesis and accelerated cancer proliferation. For example, KRAS mutations have been found in over 90% of patients with pancreatic ductal adenocarcinoma, and these mutations are present even in the early stages of pancreatic intraepithelial neoplasia (PanIN). KRAS mutations are also frequently found in lung cancer and colorectal cancer. Point mutations at codon 12 in KRAS exon 2 (e.g., KRAS G12C mutation, KRAS G12D mutation) are commonly known (Nat. Rev. Cancer, 2018, 18, pp. 767-777). In recent years, bifunctional compounds, collectively known as PROTACs (PROteolysis-TArgeting Chimeras) and SNIPERs (Specific and Nongenetic IAP-dependent Protein Erasers), have been discovered as a technology for inducing targeted protein degradation and are expected to become a novel drug discovery modality (Drug. Discov. Today Technol., 2019, 31, pp. 15-27). These bifunctional compounds promote the formation of complexes between target proteins and E3 ligases in cells, resulting in the ubiquitination of the target proteins, which then induces their degradation via the ubiquitin-proteasome system. The ubiquitin-proteasome system is one of the intracellular protein degradation mechanisms. Proteins called E3 ligases recognize and ubiquitinate proteins to be degraded, leading to their degradation via the proteasome. There are over 600 types of E3 ligases in the body, but only a limited number of E3 ligases have been used in bifunctional degradation inducers, known as PROTACs and SNIPERs, to date. Representative examples include Von Hippel-Lindau (VHL), celebron (CRBN), inhibitor of apoptosis protein (IAP), and mouse double minute 2 homolog (MDM2). These bifunctional compounds are compounds in which a ligand for a target protein and a ligand for an E3 ligase are linked via a linker. Patent Documents 1 and 2 report bifunctional compounds that reduce the level of G12D mutant KRAS protein. Patent Document 3 reports bifunctional compounds that regulate G12D mutant KRAS protein. Patent Document 4 reports compounds that degrade G12D mutant KRAS. Patent Document 5 reports quinazoline compounds for inducing degradation of G12D mutant KRAS protein. Patent Document 6 reports compounds that degrade G12D mutant KRAS. Furthermore, Patent Document 7 reports heteroaromatic compounds that degrade G12D mutant KRAS. Patent Document 8, published after the priority date of the present application, reports heterocyclic compounds for inducing degradation of G12D mutant KRAS protein, and Patent Document 9, published after the priority date of the present application, similarly reports heterocyclic compounds that act on G12D mutant KRAS protein. Meanwhile, research into technologies for selectively delivering drugs to cancer cells is progressing, including antibody-drug conjugates (ADCs), which conjugate cytotoxic drug molecules to antibodies targeting antigens expressed on the surface of cancer cells, and immune-stimulating antibody conjugates (ISACs), which conjugate immunostimulatory drug molecules. These technologies are also being used in approved pharmaceuticals (Cancer Science, 2016, Vol. 107, No. 7, pp. 1039-1046; Clinical Cancer Research, 2005, Vol. 11, pp. 843-852; Cancer Research, 2016, Vol. 76, No. 10, pp. 3003-3013). Patent documents 10-13 describe ADCs containing bifunctional compounds with the ability to induce degradation of target proteins. However, to date, no ADCs containing drugs capable of inducing degradation of the G12D mutant KRAS protein are known. International Publication No. 2022 / 148421 International Publication No. 2022 / 148422 Chinese Patent Application Publication No. 115785199 International Publication No. 2023 / 077441 International Publication No. 2022 / 173032 International Publication No. 2022 / 228576 International Publication No. 2023 / 280026 International Publication No. 2023 / 171781 International Publication No. 2024 / 019103 International Publication No. 2017 / 201449 International Publication No. 2019 / 140003 International Publication No. 2021 / 195598 International Publication No. 2023 / 056069 The present invention provides a pharmaceutical composition, particularly an antibody-drug conjugate or a salt thereof, which contains a heterocyclic compound having the activity of inducing G12D mutant KRAS proteolysis. It also provides a drug-linker conjugate or a salt thereof for use in the antibody-drug conjugate or salt thereof. As a result of extensive investigations into compounds useful as active ingredients of pharmaceutical compositions, the present inventors have found that an antibody-drug conjugate having the structure of formula (I) has an excellent activity of inducing degradation of G12D mutant KRAS proteolysis, and further found that a drug-linker conjugate containing a compound having the activity of inducing degradation of G12D mutant KRAS proteolysis is useful for synthesizing the antibody-drug conjugate, thereby completing the present invention. That is, the present invention provides the following [1] to [3].

[0045] Regarding. [1] An antibody-drug conjugate of formula (I) or a salt thereof (In the formula, Ab is an antibody or antigen-binding fragment thereof; D is a heterocyclic compound that induces the degradation of G12D mutant KRAS protein, L A is a linker for connecting Ab and D, where n is a number between 1 and 20). [2] D is a heterocyclic compound represented by formula (II), A is CR A or N, R A is H, cyano, or optionally substituted C 1-３ is alkyl, Q is CR Qor N, R Q H, halogen, C 3-６ cycloalkyl, vinyl, or optionally substituted C 1-３ is alkyl, E is CH or N; R 1 is cyano, OH, halogen, and optionally substituted C 1-３ naphthyl optionally substituted with one or two groups selected from the group consisting of alkyl, or a group selected from the group consisting of the following formula (III), formula (IV) and formula (V): R 1a , R 1b and R 1c are each independently H, vinyl, halogen, or optionally substituted C 1-３ is alkyl, R 2 -V １ -V 2 or W, V 1 represents a bond, -CH2-, -O-, -S- or -N(R V1 )- and R V1 is H or optionally substituted C 1-３ is alkyl, V 2 is a group selected from the group consisting of formula (VI) and formula (VII): W is a group selected from the group consisting of the following formulas (VIII), (IX), (X), (XI), (XII), (XIII), (XIV), (XV) and (XVI): R 2a are each independently OH, OCH3, F or optionally substituted C 1-３ alkyl, and the R 2a is bonded only to a carbon atom that is a constituent atom of a ring selected from the group consisting of an azetidine ring represented by formula (VI), a pyrrolidine ring represented by formula (VII), a piperidine ring represented by formula (VIII), and a piperazine ring represented by formula (IX), m is an integer from 0 to 2, R 3 may be substituted C 1-6 alkyl, optionally substituted heterocycloalkyl, or optionally substituted heteroaryl; X is a bond, -CH2-, -O-, -S-, or -NR 4X - and R 4X is H or optionally substituted C 1-３ is alkyl, Y 1 is -O-(optionally substituted C 1-３ alkylene)- ＊Y2 , -S-(optionally substituted C 1-３ alkylene)- ＊Y2 , -SO2-(optionally substituted C 1-３ alkylene)- ＊Y2 , -NR Y -(optionally substituted C 1-３ alkylene)- ＊Y2 , -(optionally substituted C 1-３ alkylene)-O- ＊Y2 , -(optionally substituted C 1-３ Alkylene)-S- ＊Y2 , -(optionally substituted C 1-３ Alkylene)-SO2- ＊Y2 or -(optionally substituted C 1-３ (Alkylene)-NR Y - ＊Y2 And ( ＊Y2 is Y 2 ) R Y is H or optionally substituted C 1-３ is alkyl, Y 2 is a bond, optionally substituted phenylene or optionally substituted heteroarylene; L P is Y 2 and EUB, EUB is a group capable of binding to one E3 ubiquitin ligase selected from the group consisting of VHL, cereblon, IAP, MDM2, DCAF11, DCAF15, DCAF16, BIRC2, KEAP1, RNF4, RNF114, FEM1B, and AhR; L A is a linker for connecting Ab and D, where L A is bonded to any nitrogen atom of —NH— or oxygen atom of —OH contained in D, or a salt thereof. [3] V 2 is a group selected from the group consisting of the following formula (VIa) and formula (VIIa): *LA is L A ) W is a group selected from the group consisting of the following formulas (VIIIa), (IXa), (Xa), (XIa), (XIIa), (XIIIa), (XIVa), (XVa), and (XVIa): *LA L A ) L A is a linker for connecting Ab and D, where L A is V 2 or nitrogen atoms contained in W *LA The antibody-drug conjugate or salt thereof according to [2], which binds to D at a binding site represented by [4] A is N, Q is CR Q and R Q is cyclopropyl, E is CH; R 1 is the following formula (III-2), R 2 But -V 1 -V 2 or W, V 1 is -N(CH3)-, V 2 is the following formula (VII-2), W is represented by the following formula (XIV): R 3 is n-propyl optionally substituted with —OCH3, or tetrahydropyranyl, X is -O-, Y 1 But -O-(methylene)- ＊Y2 And ( ＊Y2 is Y 2 ) Y 2 is phenylene, L P But, Y 2 and EUB, The antibody-drug conjugate or salt thereof according to [2], wherein EUB is a group capable of binding to an E3 ubiquitin ligase selected from the group consisting of VHL and cereblon. [5] V 2 is the following formula (VII-2a) ( *LA L A ) W is represented by the following formula (XIVa): *LA L A ) L A is a linker for connecting Ab and D, where L A is V 2 or nitrogen atoms contained in W *LA The antibody-drug conjugate or salt thereof according to [4], which binds to D at a binding site represented by [6] D. (4R)-1-[(2S)-2-(4-{4-[({6-cyclopropyl-4-[(1S,4S)-2,5-diazabicyclo[2.2.1]heptan-2-yl]-7-(6-fluoro-5-methyl-1H-indazol-4-yl)-2-[(oxan-4-yl)oxy]quinazolin-8-yl}oxy)methyl]phenyl}-1H-1,2,3-triazol-1-yl)-3-methylbutanoyl]-4-hydroxy-N-{(1R)-2-hydroxy-1-[4-(4-methyl-1,3-thiazol-5-yl)phenyl]ethyl}-L-prolinamide, (4R)-1-[(2S)-2-(4-{4-[({6-cyclopropyl-4-[(1S,4S)-2,5-diazabicyclo[2.2.1]heptan-2-yl]-7-(6-fluoro-5-methyl-1H-indazol-4-yl)-2-[(oxan-4-yl)oxy]quinazolin-8-yl}oxy)methyl]phenyl}-1H-1,2,3-triazol-1-yl)-3-methylbutanoyl]-4-hydroxy-N-{(1R)-2-hydroxy-1-[4-(2-oxo-1,3-oxazolidin-3-yl)phenyl]ethyl}-L-prolinamide, (4R)-1-[(2S)-2-(4-{4-[({6-cyclopropyl-4-[(1S,4S)-2,5-diazabicyclo[2.2.1]heptan-2-yl]-7-(6-fluoro-5-methyl-1H-indazol-4-yl)-2-[(oxan-4-yl)oxy]quinazolin-8-yl}oxy)methyl]phenyl}-1H-1,2,3-triazol-1-yl)-3-methylbutanoyl]-4-hydroxy-N-{(1R)-2-hydroxy-1-[4-(1-methyl-1H-pyrazol-5-yl)phenyl]ethyl}-L-prolinamide, (4R)-1-[(2S)-2-(4-{4-[({6-cyclopropyl-4-[(1S,4S)-2,5-diazabicyclo[2.2.1]heptan-2-yl]-7-(6-fluoro-5-methyl-1H-indazol-4-yl)-2-[(2S)-2-methoxypropoxy]quinazolin-8-yl}oxy)methyl]phenyl}-1H-1,2,3-triazol-1-yl)-3-methylbutanoyl]-4-hydroxy-N-{(1R)-2-hydroxy-1-[4-(4-methyl-1,3-thiazol-5-yl)phenyl]ethyl}-L-prolinamide, (4R)-1-[(2S)-2-(4-{4-[({6-cyclopropyl-4-[(1S,4S)-2,5-diazabicyclo[2.2.1]heptan-2-yl]-7-(6-fluoro-5-methyl-1H-indazol-4-yl)-2-[(2S)-2-methoxypropoxy]quinazolin-8-yl}oxy)methyl]phenyl}-1H-1,2,3-triazol-1-yl)-3-methylbutanoyl]-N-{(1R)-1-[4-(1-ethyl-1H-pyrazol-5-yl)phenyl]-2-hydroxyethyl}-4-hydroxy-L-prolinamide, (4R)-1-[(2S)-2-(4-{4-[({6-cyclopropyl-4-[(1S,4S)-2,5-diazabicyclo[2.2.1]heptan-2-yl]-7-(6-fluoro-5-methyl-1H-indazol-4-yl)-2-[(2S)-2-methoxypropoxy]quinazolin-8-yl}oxy)methyl]phenyl}-1H-1,2,3-triazol-1-yl)-3-methylbutanoyl]-4-hydroxy-N-{(1R)-2-hydroxy-1-[4-(4-methyl-1,3-oxazol-5-yl)phenyl]ethyl}-L-prolinamide, (4R)-1-[(2S)-2-{4-[4-({[(7M)-6-cyclopropyl-7-(6-fluoro-5-methyl-1H-indazol-4-yl)-2-[(2S)-2-methoxypropoxy]-4-{methyl[(3S)-pyrrolidin-3-yl]amino}quinazolin-8-yl]oxy}methyl)phenyl]-1H-1,2,3-triazol-1-yl}-3-methylbutanoyl]-4-hydroxy-N-{(1R)-2-hydroxy-1-[4-(4-methyl-1,3-thiazol-5-yl)phenyl]ethyl}-L-prolinamide, (4R)-1-[(2S)-2-{4-[4-({[(7M)-6-cyclopropyl-7-(6-fluoro-5-methyl-1H-indazol-4-yl)-2-[(2S)-2-methoxypropoxy]-4-{methyl[(3S)-pyrrolidin-3-yl]amino}quinazolin-8-yl]oxy}methyl)phenyl]-1H-1,2,3-triazol-1-yl}-3-methylbutanoyl]-N-{(1R)-1-[4-(1-ethyl-1H-pyrazol-5-yl)phenyl]-2-hydroxyethyl}-4-hydroxy-L-prolinamide, 3-(5-{[(3S)-4-{4-[({(7M)-6-cyclopropyl-4-[(1S,4S)-2,5-diazabicyclo[2.2.1]heptan-2-yl]-7-(6-fluoro-5-methyl-1H-indazol-4-yl)-2-[(oxan-4-yl)oxy]quinazolin-8-yl}oxy)methyl]benzoyl}-3-methylpiperazin-1-yl]methyl}-3-methyl-2-oxo-2,3-dihydro-1H-benzimidazol-1-yl)piperidine-2,6-dione, 1-(6-{[(3S)-4-{4-[({(7M)-6-cyclopropyl-4-[(1S,4S)-2,5-diazabicyclo[2.2.1]heptan-2-yl]-7-(6-fluoro-5-methyl-1H-indazol-4-yl)-2-[(oxan-4-yl)oxy]quinazolin-8-yl}oxy)methyl]benzoyl}-3-methylpiperazin-1-yl]methyl}-1-methyl-1H-indazol-3-yl)-1,3-diazinan-2,4-dione, 3-(5-{[(3S)-4-{4-[({(7M)-6-cyclopropyl-4-[(1S,4S)-2,5-diazabicyclo[2.2.1]heptan-2-yl]-7-(6-fluoro-5-methyl-1H-indazol-4-yl)-2-[(2S)-2-methoxypropoxy]quinazolin-8-yl}oxy)methyl]benzoyl}-3-methylpiperazin-1-yl]methyl}-3-methyl-2-oxo-2,3-dihydro-1H-benzimidazol-1-yl)piperidine-2,6-dione, or The antibody-drug conjugate or salt thereof according to either one of [1] or [2], wherein phosphate = dihydrogen = (2R)-2-({(4R)-1-[(2S)-2-{4-[4-({[(7M)-6-cyclopropyl-7-(6-fluoro-5-methyl-1H-indazol-4-yl)-2-[(2S)-2-methoxypropoxy]-4-{methyl[(3S)-pyrrolidin-3-yl]amino}quinazolin-8-yl]oxy}methyl)phenyl]-1H-1,2,3-triazol-1-yl}-3-methylbutanoyl]-4-hydroxy-L-prolyl}amino)-2-[4-(1H-1,2,4-triazol-1-yl)phenyl]ethyl. [7] L A is a linker represented by formula (XXVIII): (In the formula, Str is a stretcher unit that binds to Ab and CLL, and r is 0 or 1; CLL is a partial structure that can be cleaved in vivo. Sp is a spacer unit and binds to CLL and D; t is 0 or 1; *Ab indicates the Ab binding site). [8] The antibody-drug conjugate or salt thereof according to [7], wherein Str is a stretcher unit represented by formula (ST-1) and r is 1. (In the formula, R st1 may be substituted C 1-12 Alkylene, -(CH2CH2O) a1 -C 1-6Alkylene-, -C 1-6 Alkylene-(OCH2CH2) a2 -, -Optionally substituted C 1-6 Alkylene-NH-C(=O)-optionally substituted C 1-6 Alkylene-, -optionally substituted C 1-6 Alkylene-C(=O)-NH-optionally substituted C 1-6 Alkylene-, optionally substituted C 1-6 Alkylene-C(=O)-NH-(CH2CH2O) a3 -C 1-6 Alkylene- or optionally substituted C 1-6 Alkylene-NH-C(=O)-(CH2CH2O) a4 -C 1-6 alkylene-, a1, a2, a3, and a4 are each an integer from 1 to 10, *Ab indicates the Ab binding site). [9] R st1 is C5 alkylene, or a salt thereof according to [8].

[0010] An antibody-drug conjugate or a salt thereof described in [7], wherein CLL is a partial structure cleavable in vivo and represented by formula (CL-1). (In the formula, R AA are each independently H, methyl, isopropyl, isobutyl, sec-butyl, benzyl, p-hydroxybenzyl, hydroxymethyl, 1-hydroxyethyl, -CH2-C(=O)-OH, -(CH2)2-C(=O)-OH, -CH2-C(=O)-NH2, -(CH2)2-C(=O)-NH2, -(CH2)4-NH2, -(CH2)3-NH-C(=NH)-NH2, -(CH2)3-NH-C(=O)-NH2, -CH2-SH, or -CH2-S-CH3, or a group selected from the group consisting of the following formulae (RAA-1) and (RAA-2), d is an integer from 1 to 6, *STR indicates the binding site with Str). [10a] R AAare each independently H, methyl, isopropyl, benzyl, -(CH2)4-NH2, -(CH2)3-NH-C(=NH)-NH2, or -(CH2)3-NH-C(=O)-NH2, and d is an integer of 2 to 4. An antibody-drug conjugate or a salt thereof according to

[0010] . [10b] R AA are, independently of each other, methyl, isopropyl, benzyl, -(CH2)4-NH2, -(CH2)3-NH-C(=NH)-NH2, or -(CH2)3-NH-C(=O)-NH2, and d is 2. An antibody-drug conjugate or salt thereof according to

[0010] . [10c] R AA are each independently methyl, isopropyl, or —(CH2)3—NH—C(═O)—NH2, and d is 2, or a salt thereof according to

[0010] .

[0011] R AA are each independently methyl or isopropyl, and d is 2.

[0012] R AA are each independently isopropyl or -(CH2)3-NH-C(=O)-NH2, and d is 2, or a salt thereof according to

[0010] .

[0013] R AA are each independently H or benzyl, and d is 4, or a salt thereof according to

[0010] .

[0014] The antibody-drug conjugate or salt thereof according to [7], wherein Sp is a spacer unit represented by formula (SP-1) and t is 1. (In the formula, R SP is H, C 1-6 Alkyl, -OC 1-6 Alkyl, halogen, or halogenoC 1-6 is alkyl, *CLL indicates the junction with CLL.

[0015] R SP is H. The antibody-drug conjugate or salt thereof according to

[0014] .

[0016] The antibody-drug conjugate or salt thereof according to [7], wherein t is 0.

[0017] The antibody-drug conjugate or salt thereof according to [1], wherein formula (I) is represented by formula (AD-1a) or (AD-2a): (In the formula, Ab is an antibody or antigen-binding fragment thereof; A is CR A or N, R A is H, cyano, or optionally substituted C 1-３ is alkyl, Q is CR Q or N, R Q H, halogen, C 3-６ cycloalkyl, vinyl, or optionally substituted C 1-３ is alkyl, E is CH or N; R 1 is cyano, OH, halogen, and optionally substituted C 1-３ naphthyl optionally substituted with one or two groups selected from the group consisting of alkyl, or a group selected from the group consisting of the following formula (III), formula (IV) and formula (V): R 1a , R 1b and R 1c are each independently H, vinyl, halogen, or optionally substituted C 1-３ is alkyl, R 3 may be substituted C 1-6 alkyl, optionally substituted heterocycloalkyl, or optionally substituted heteroaryl; X is a bond, -CH2-, -O-, -S-, or -NR 4X - and R 4X is H or optionally substituted C 1-３ is alkyl, Y 1 is -O-(optionally substituted C 1-３alkylene)- ＊Y2 , -S-(optionally substituted C 1-３ alkylene)- ＊Y2 , -SO2-(optionally substituted C 1-３ alkylene)- ＊Y2 , -NR Y -(optionally substituted C 1-３ alkylene)- ＊Y2 , -(optionally substituted C 1-３ alkylene)-O- ＊Y2 , -(optionally substituted C 1-３ Alkylene)-S- ＊Y2 , -(optionally substituted C 1-３ Alkylene)-SO2- ＊Y2 or -(optionally substituted C 1-３ (Alkylene)-NR Y - ＊Y2 And ( ＊Y2 is Y 2 ) R Y is H or optionally substituted C 1-３ is alkyl, Y 2 is a bond, optionally substituted phenylene or optionally substituted heteroarylene; L P is Y 2 and EUB, EUB is a group capable of binding to one E3 ubiquitin ligase selected from the group consisting of VHL, cereblon, IAP, MDM2, DCAF11, DCAF15, DCAF16, BIRC2, KEAP1, RNF4, RNF114, FEM1B, and AhR; R st1 is C 1-12 is alkylene, R AA are each independently H, methyl, isopropyl, benzyl, or —(CH)—NH—C(═O)—NH, and d is an integer from 2 to 4; t is 0 or 1, where n is a number between 1 and 20).

[0018] The antibody-drug conjugate or salt thereof described in [1], wherein formula (I) is represented by formula (AD-3a), (AD-4a), (AD-5a), (AD-6a), (AD-7a), (AD-8a), (AD-9a), (AD-10a), (AD-11a), (AD-12a), (AD-13a), or (AD-25a). (In the formula, R st1 is C 1-12 alkylene, and R AA are each independently H, methyl, isopropyl, benzyl, or -(CH2)3-NH-C(=O)-NH2, d is an integer of 2 to 4, t is 0 or 1, and n is a number of 1 to 20. Compounds with an "*" in the chemical structural formula indicate that the compound has a single axial or central chirality. The same applies below.

[0019] The antibody-drug conjugate or salt thereof described in [1], wherein formula (I) is represented by formula (AD-14), (AD-15), (AD-16), (AD-17), (AD-18), (AD-19), (AD-20), (AD-21), (AD-22), (AD-23), (AD-24), or (AD-25). (wherein n is a number from 1 to 20).

[0020] An antibody-drug conjugate or a salt thereof described in any one of [1] to

[0019] , wherein Ab is cetuximab and n is a number between 2 and 5.

[0021] Ab, 5T4, ADAM9, ALPP, ALPPL2, AXL, B7H3, B7H4, BCMA, CA9, CCR2, CCR7, CD123, CD166, CD19, CD20, CD22, CD25, CD30, CD33, CD37, CD38, CD45, CD46, CD70, CD74, CD79b, CDH3, CDH6, CLDN1, CLDN4, CLDN6, CLDN18.2, cMET, EGFR, EphA3, FAP, FGFR3, Fibronectin, FOLRa, Globo H, GPRC5D, HER2, HER3, IGF1R, Integrin The antibody-drug conjugate or salt thereof according to any one of [1] to

[0019] , which is an antibody or antigen-binding fragment that binds to one or more antigens selected from the group consisting of αV, KAAG1, LIV1, MSLN, MT1-MMP, MUC1, MUC4, NaPi2b, Nectin4, PD-L1, PSMA, PTK7, ROR1, ROR2, SEZ6, SialylTn, TF, TROP2, TSPAN8, and VEGF.

[0022] An antibody-drug conjugate or a salt thereof described in any one of [1] to

[0019] , wherein Ab is an antibody or antigen-binding fragment that binds to one or more antigens selected from the group consisting of EGFR, HER2, cMET, and TROP2.

[0023] An antibody-drug conjugate or a salt thereof described in any one of [1] to

[0019] , wherein Ab is an anti-EGFR antibody or an antigen-binding fragment thereof.

[0024] The antibody-drug conjugate or salt thereof according to

[0023] , wherein Ab is an anti-EGFR antibody or an antigen-binding fragment thereof comprising a heavy chain variable region and a light chain variable region according to the following (1) or (2): (1) a heavy chain variable region comprising CDR1 consisting of the amino acid sequence from amino acid numbers 31 to 35 of SEQ ID NO: 1, CDR2 consisting of the amino acid sequence from amino acid numbers 50 to 65 of SEQ ID NO: 1, and CDR3 consisting of the amino acid sequence from amino acid numbers 98 to 108 of SEQ ID NO: 1; and a light chain variable region comprising a CDR1 consisting of the amino acid sequence from amino acid numbers 24 to 34 of SEQ ID NO: 2, a CDR2 consisting of the amino acid sequence from amino acid numbers 50 to 56 of SEQ ID NO: 2, and a CDR3 consisting of the amino acid sequence from amino acid numbers 89 to 97 of SEQ ID NO: 2; or (2) a heavy chain variable region comprising CDR1 consisting of the amino acid sequence of amino acids 31 to 35 of SEQ ID NO: 3, CDR2 consisting of the amino acid sequence of amino acids 50 to 65 of SEQ ID NO: 3, and CDR3 consisting of the amino acid sequence of amino acids 98 to 108 of SEQ ID NO: 3; and A light chain variable region comprising CDR1 consisting of the amino acid sequence from amino acid numbers 24 to 34 of SEQ ID NO: 4, CDR2 consisting of the amino acid sequence from amino acid numbers 50 to 56 of SEQ ID NO: 4, and CDR3 consisting of the amino acid sequence from amino acid numbers 89 to 97 of SEQ ID NO: 4.

[0025] The antibody-drug conjugate or salt thereof according to

[0023] , wherein Ab is an anti-EGFR antibody or an antigen-binding fragment thereof comprising a heavy chain variable region and a light chain variable region selected from the group consisting of the following (1) to (3): (1) a heavy chain variable region consisting of the amino acid sequence from amino acid numbers 1 to 119 of SEQ ID NO: 1 and a light chain variable region consisting of the amino acid sequence from amino acid numbers 1 to 107 of SEQ ID NO: 2; (2) a heavy chain variable region consisting of the amino acid sequence from amino acid numbers 1 to 119 of SEQ ID NO: 3 and a light chain variable region consisting of the amino acid sequence from amino acid numbers 1 to 107 of SEQ ID NO: 4; and (3) A heavy chain variable region and a light chain variable region having at least 90% identity to the heavy chain variable region and the light chain variable region described in (1) or (2) above.

[0026] An antibody-drug conjugate or a salt thereof according to

[0023] , wherein Ab is an IgG1 or IgG4 type anti-EGFR antibody.

[0027] An antibody-drug conjugate or a salt thereof described in

[0023] , wherein Ab is an anti-EGFR antibody consisting of a heavy chain of sequence number 1 and a light chain of sequence number 2.

[0028] An antibody-drug conjugate or a salt thereof described in any one of

[0021] to

[0023] , wherein the Ab is an antibody that has been post-translationally modified or in which any amino acid residue has been substituted with cysteine ​​or a non-natural amino acid.

[0029] A pharmaceutical composition comprising an antibody-drug conjugate or a salt thereof described in any one of [1] to

[0028] and a pharmaceutically acceptable excipient.

[0030] A pharmaceutical composition described in

[0029] for use in the treatment of cancer.

[0031] A pharmaceutical composition described in

[0030] , wherein the cancer is a blood cancer or a solid cancer.

[0032] A pharmaceutical composition described in

[0030] , wherein the cancer is a cancer expressing G12D mutant KRAS.

[0033] An antibody-drug conjugate or a salt thereof described in any one of [1] to

[0028] for use in the treatment of cancer.

[0034] A method for treating cancer, comprising the step of administering to a subject a therapeutically effective amount of an antibody-drug conjugate or a salt thereof described in any one of [1] to

[0028] .

[0035] Use of an antibody-drug conjugate or a salt thereof described in any one of [1] to

[0028] in the manufacture of a pharmaceutical composition for the treatment of cancer.

[0036] A drug-linker conjugate represented by formula (LD-1) or a salt thereof (In the formula, D is a heterocyclic compound that induces the degradation of G12D mutant KRAS protein, R st1 is C 1-12 is alkylene, CLL is a partial structure that can be cleaved in vivo. Sp is a spacer unit that binds to CLL and D, and t is 0 or 1. D is a heterocyclic compound represented by formula (II): A is CR A or N, R A is H, cyano, or optionally substituted C 1-３is alkyl, Q is CR Q or N, R Q H, halogen, C 3-６ cycloalkyl, vinyl, or optionally substituted C 1-３ is alkyl, E is CH or N; R 1 is cyano, OH, halogen, and optionally substituted C 1-３ naphthyl optionally substituted with one or two groups selected from the group consisting of alkyl, or a group selected from the group consisting of the following formula (III), formula (IV) and formula (V): R 1a , R 1b and R 1c are each independently H, vinyl, halogen, or optionally substituted C 1-３ is alkyl, R 2 -V １ -V 2 or W, V 1 represents a bond, -CH2-, -O-, -S- or -N(R V1 )- and R V1 is H or optionally substituted C 1-３ is alkyl, V 2 is a group selected from the group consisting of formula (VI) and formula (VII): W is a group selected from the group consisting of the following formulas (VIII), (IX), (X), (XI), (XII), (XIII), (XIV), (XV) and (XVI): R 2a are each independently OH, OCH3, F or optionally substituted C 1-３ alkyl, and the R 2ais bonded only to a carbon atom that is a constituent atom of a ring selected from the group consisting of an azetidine ring represented by formula (VI), a pyrrolidine ring represented by formula (VII), a piperidine ring represented by formula (VIII), and a piperazine ring represented by formula (IX), m is an integer from 0 to 2, R 3 may be substituted C 1-6 alkyl, optionally substituted heterocycloalkyl, or optionally substituted heteroaryl; X is a bond, -CH2-, -O-, -S-, or -NR 4X - and R 4X is H or optionally substituted C 1-３ is alkyl, Y 1 is -O-(optionally substituted C 1-３ alkylene)- ＊Y2 , -S-(optionally substituted C 1-３ alkylene)- ＊Y2 , -SO2-(optionally substituted C 1-３ alkylene)- ＊Y2 , -NR Y -(optionally substituted C 1-３ alkylene)- ＊Y2 , -(optionally substituted C 1-３ alkylene)-O- ＊Y2 , -(optionally substituted C 1-３ Alkylene)-S- ＊Y2 , -(optionally substituted C 1-３ Alkylene)-SO2- ＊Y2 or -(optionally substituted C 1-３ (Alkylene)-NR Y - ＊Y2 And ( ＊Y2 is Y 2 ) R Y is H or optionally substituted C 1-３ is alkyl, Y 2 is a bond, optionally substituted phenylene or optionally substituted heteroarylene; LP is Y 2 and EUB, EUB is a group capable of binding to one E3 ubiquitin ligase selected from the group consisting of VHL, cereblon, IAP, MDM2, DCAF11, DCAF15, DCAF16, BIRC2, KEAP1, RNF4, RNF114, FEM1B, and AhR; A drug-linker conjugate or a salt thereof described in

[0036] , wherein Sp is a spacer unit and binds to CLL and D, and wherein Sp binds to any nitrogen atom of -NH- or oxygen atom of -OH contained in D.

[0038] V 2 is a group selected from the group consisting of the following formula (VIb) and formula (VIIb): *SP indicates the bond with Sp.) W is a group selected from the group consisting of the following formulas (VIIIb), (IXb), (Xb), (XIb), (XIIb), (XIIIb), (XIVb), (XVb), and (XVIb): *SP indicates the bond with Sp.) Sp is a spacer unit and binds to CLL and D, where Sp is V 2 or nitrogen atoms contained in W ＊SP The drug-linker conjugate or salt thereof according to

[0037] , which is bound to D at a bonding site represented by: A is N; Q is CR Q and R Q is cyclopropyl, E is CH; R 1 is the following formula (III-2), R 2 But -V 1 -V 2 or W, V 1 is -N(CH3)-, V 2 is the following formula (VII-2), W is represented by the following formula (XIV): R 3 is n-propyl optionally substituted with —OCH3, or tetrahydropyranyl, X is -O-, Y 1 But -O-(methylene)- ＊Y2 And ( ＊Y2 is Y 2 ) Y 2 is phenylene, L P But, Y 2 and EUB, A drug-linker conjugate or a salt thereof described in

[0037] , wherein EUB is a group capable of binding to an E3 ubiquitin ligase selected from the group consisting of VHL and cereblon.

[0040] V 2 is the following formula (VII-2b) ( *SP indicates the bond with Sp.) W is represented by the following formula (XIVb): *SP indicates the bond with Sp.) Sp is a spacer unit and binds to CLL and D, where Sp is V 2 or nitrogen atoms contained in W ＊SP The drug-linker conjugate or salt thereof according to

[0039] , which is bound to D at a bonding site represented by the following formula: D is (4R)-1-[(2S)-2-(4-{4-[({6-cyclopropyl-4-[(1S,4S)-2,5-diazabicyclo[2.2.1]heptan-2-yl]-7-(6-fluoro-5-methyl-1H-indazol-4-yl)-2-[(oxan-4-yl)oxy]quinazolin-8-yl}oxy)methyl]phenyl}-1H-1,2,3-triazol-1-yl)-3-methylbutanoyl]-4-hydroxy-N-{(1R)-2-hydroxy-1-[4-(4-methyl-1,3-thiazol-5-yl)phenyl]ethyl}-L-prolinamide, (4R)-1-[(2S)-2-(4-{4-[({6-cyclopropyl-4-[(1S,4S)-2,5-diazabicyclo[2.2.1]heptan-2-yl]-7-(6-fluoro-5-methyl-1H-indazol-4-yl)-2-[(oxan-4-yl)oxy]quinazolin-8-yl}oxy)methyl]phenyl}-1H-1,2,3-triazol-1-yl)-3-methylbutanoyl]-4-hydroxy-N-{(1R)-2-hydroxy-1-[4-(2-oxo-1,3-oxazolidin-3-yl)phenyl]ethyl}-L-prolinamide, (4R)-1-[(2S)-2-(4-{4-[({6-cyclopropyl-4-[(1S,4S)-2,5-diazabicyclo[2.2.1]heptan-2-yl]-7-(6-fluoro-5-methyl-1H-indazol-4-yl)-2-[(oxan-4-yl)oxy]quinazolin-8-yl}oxy)methyl]phenyl}-1H-1,2,3-triazol-1-yl)-3-methylbutanoyl]-4-hydroxy-N-{(1R)-2-hydroxy-1-[4-(1-methyl-1H-pyrazol-5-yl)phenyl]ethyl}-L-prolinamide, (4R)-1-[(2S)-2-(4-{4-[({6-cyclopropyl-4-[(1S,4S)-2,5-diazabicyclo[2.2.1]heptan-2-yl]-7-(6-fluoro-5-methyl-1H-indazol-4-yl)-2-[(2S)-2-methoxypropoxy]quinazolin-8-yl}oxy)methyl]phenyl}-1H-1,2,3-triazol-1-yl)-3-methylbutanoyl]-4-hydroxy-N-{(1R)-2-hydroxy-1-[4-(4-methyl-1,3-thiazol-5-yl)phenyl]ethyl}-L-prolinamide, (4R)-1-[(2S)-2-(4-{4-[({6-cyclopropyl-4-[(1S,4S)-2,5-diazabicyclo[2.2.1]heptan-2-yl]-7-(6-fluoro-5-methyl-1H-indazol-4-yl)-2-[(2S)-2-methoxypropoxy]quinazolin-8-yl}oxy)methyl]phenyl}-1H-1,2,3-triazol-1-yl)-3-methylbutanoyl]-N-{(1R)-1-[4-(1-ethyl-1H-pyrazol-5-yl)phenyl]-2-hydroxyethyl}-4-hydroxy-L-prolinamide, (4R)-1-[(2S)-2-(4-{4-[({6-cyclopropyl-4-[(1S,4S)-2,5-diazabicyclo[2.2.1]heptan-2-yl]-7-(6-fluoro-5-methyl-1H-indazol-4-yl)-2-[(2S)-2-methoxypropoxy]quinazolin-8-yl}oxy)methyl]phenyl}-1H-1,2,3-triazol-1-yl)-3-methylbutanoyl]-4-hydroxy-N-{(1R)-2-hydroxy-1-[4-(4-methyl-1,3-oxazol-5-yl)phenyl]ethyl}-L-prolinamide, (4R)-1-[(2S)-2-{4-[4-({[(7M)-6-cyclopropyl-7-(6-fluoro-5-methyl-1H-indazol-4-yl)-2-[(2S)-2-methoxypropoxy]-4-{methyl[(3S)-pyrrolidin-3-yl]amino}quinazolin-8-yl]oxy}methyl)phenyl]-1H-1,2,3-triazol-1-yl}-3-methylbutanoyl]-4-hydroxy-N-{(1R)-2-hydroxy-1-[4-(4-methyl-1,3-thiazol-5-yl)phenyl]ethyl}-L-prolinamide, (4R)-1-[(2S)-2-{4-[4-({[(7M)-6-cyclopropyl-7-(6-fluoro-5-methyl-1H-indazol-4-yl)-2-[(2S)-2-methoxypropoxy]-4-{methyl[(3S)-pyrrolidin-3-yl]amino}quinazolin-8-yl]oxy}methyl)phenyl]-1H-1,2,3-triazol-1-yl}-3-methylbutanoyl]-N-{(1R)-1-[4-(1-ethyl-1H-pyrazol-5-yl)phenyl]-2-hydroxyethyl}-4-hydroxy-L-prolinamide, 3-(5-{[(3S)-4-{4-[({(7M)-6-cyclopropyl-4-[(1S,4S)-2,5-diazabicyclo[2.2.1]heptan-2-yl]-7-(6-fluoro-5-methyl-1H-indazol-4-yl)-2-[(oxan-4-yl)oxy]quinazolin-8-yl}oxy)methyl]benzoyl}-3-methylpiperazin-1-yl]methyl}-3-methyl-2-oxo-2,3-dihydro-1H-benzimidazol-1-yl)piperidine-2,6-dione, 1-(6-{[(3S)-4-{4-[({(7M)-6-cyclopropyl-4-[(1S,4S)-2,5-diazabicyclo[2.2.1]heptan-2-yl]-7-(6-fluoro-5-methyl-1H-indazol-4-yl)-2-[(oxan-4-yl)oxy]quinazolin-8-yl}oxy)methyl]benzoyl}-3-methylpiperazin-1-yl]methyl}-1-methyl-1H-indazol-3-yl)-1,3-diazinan-2,4-dione, 3-(5-{[(3S)-4-{4-[({(7M)-6-cyclopropyl-4-[(1S,4S)-2,5-diazabicyclo[2.2.1]heptan-2-yl]-7-(6-fluoro-5-methyl-1H-indazol-4-yl)-2-[(2S)-2-methoxypropoxy]quinazolin-8-yl}oxy)methyl]benzoyl}-3-methylpiperazin-1-yl]methyl}-3-methyl-2-oxo-2,3-dihydro-1H-benzimidazol-1-yl)piperidine-2,6-dione, or Dihydrogen phosphate = (2R)-2-({(4R)-1-[(2S)-2-{4-[4-({[(7M)-6-cyclopropyl-7-(6-fluoro-5-methyl-1H-indazol-4-yl)-2-[(2S)-2-methoxypropoxy]-4-{methyl[(3S)-pyrrolidin-3-yl]amino}quinazolin-8-yl]oxy}methyl)phenyl]-1H-1,2,3-triazol-1-yl}-3-methylbutanoyl]-4-hydroxy-L-prolyl}amino)-2-[4-(1H-1,2,4-triazol-1-yl)phenyl]ethyl A drug-linker conjugate or a salt thereof according to any one of

[0036] or

[0037] ,

[0042] The drug-linker conjugate or salt thereof according to

[0036] , wherein formula (LD-1) is represented by formula (LD-2a) or (LD-3a): (In the formula, A is CR A or N, R A is H, cyano, or optionally substituted C 1-３ is alkyl, Q is CR Q or N, R Q H, halogen, C 3-６ cycloalkyl, vinyl, or optionally substituted C 1-３ is alkyl, E is CH or N; R 1 is cyano, OH, halogen, and optionally substituted C 1-３naphthyl optionally substituted with one or two groups selected from the group consisting of alkyl, or a group selected from the group consisting of the following formula (III), formula (IV) and formula (V): R 1a , R 1b and R 1c are each independently H, vinyl, halogen, or optionally substituted C 1-３ is alkyl, R 3 may be substituted C 1-6 alkyl, optionally substituted heterocycloalkyl, or optionally substituted heteroaryl; X is a bond, -CH2-, -O-, -S-, or -NR 4X - and R 4X is H or optionally substituted C 1-３ is alkyl, Y 1 is -O-(optionally substituted C 1-３ alkylene)- ＊Y2 , -S-(optionally substituted C 1-３ alkylene)- ＊Y2 , -SO2-(optionally substituted C 1-３ alkylene)- ＊Y2 , -NR Y -(optionally substituted C 1-３ alkylene)- ＊Y2 , -(optionally substituted C 1-３ alkylene)-O- ＊Y2 , -(optionally substituted C 1-３ Alkylene)-S- ＊Y2 , -(optionally substituted C 1-３ Alkylene)-SO2- ＊Y2 or -(optionally substituted C 1-３ (Alkylene)-NR Y - ＊Y2 And ( ＊Y2 is Y 2 ) R Y is H or optionally substituted C 1-３ is alkyl, Y 2 is a bond, optionally substituted phenylene or optionally substituted heteroarylene; L P is Y 2 and EUB, EUB is a group capable of binding to an E3 ubiquitin ligase selected from the group consisting of VHL and cereblon; R st1 is C 1-12 is alkylene, R AA are each independently H, methyl, isopropyl, benzyl, or —(CH2)3—NH—C(═O)—NH2, d is an integer from 2 to 4, and t is 0 or 1.

[0043] A drug-linker conjugate or a salt thereof according to

[0036] , wherein formula (LD-1) is represented by formula (LD-4a), (LD-5a), (LD-6a), (LD-7a), (LD-8a), (LD-9a), (LD-10a), (LD-11a), (LD-12a), (LD-13a), (LD-14a), or (LD-26a). (In the formula, R st1 is C 1-12 alkylene, and R AA are each independently H, methyl, isopropyl, benzyl, or —(CH 2 ) 3 —NH—C(═O)—NH 2 , d is an integer from 2 to 4, and t is 0 or 1.

[0044] A drug-linker complex or a salt thereof described in

[0036] , wherein formula (LD-1) is represented by formula (LD-15), (LD-16), (LD-17), (LD-18), (LD-19), (LD-20), (LD-21), (LD-22), (LD-23), (LD-24), (LD-25), or (LD-26).

[0045] Phosphate = dihydrogen = (2R)-2-({(4R)-1-[(2S)-2-{4-[4-({[(7M)-6-cyclopropyl-7-(6-fluoro-5-methyl-1H-indazol-4-yl)-2-[(2S)-2-methoxypropoxy]-4-{methyl[(3S)-pyrrolidin-3-yl]amino}quinazolin-8-yl]oxy}methyl)phenyl]-1H-1,2,3-triazol-1-yl}-3-methylbutanoyl]-4-hydroxy-L-prolyl}amino)-2-[4-(1H-1,2,4-triazol-1-yl)phenyl]ethyl or its salt. Unless otherwise specified, when a symbol in a chemical formula in this specification is used in other chemical formulas, the same symbol has the same meaning. The antibody-drug conjugate of formula (I) or a salt thereof has the activity of inducing G12D mutant KRAS proteolysis and can be used as a therapeutic agent for cancer, particularly cancer expressing G12D mutant KRAS. Furthermore, the drug-linker conjugate of the present invention contains a compound having the activity of inducing G12D mutant KRAS proteolysis and can be used to synthesize the antibody-drug conjugate of the present invention or a salt thereof. The present invention will be described in detail below. In this specification, "optionally substituted" means unsubstituted or having 1 to 5 substituents. In one embodiment, it means unsubstituted or having 1 to 3 substituents. When there are multiple substituents, the substituents may be the same or different from each other. "C 1-12 The term "alkyl" refers to a straight-chain or branched alkyl having 1 to 12 carbon atoms, such as methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, n-hexyl, dodecyl, etc. (Hereinafter, the number of carbon atoms will be expressed in the same manner.) In one embodiment, it is ethyl or dodecyl. Similarly, "C 1-6The term "alkyl" refers to a straight-chain or branched alkyl having 1 to 6 carbon atoms, for example, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, or n-hexyl; in one embodiment, methyl, ethyl, n-propyl, isopropyl, or sec-butyl; in one embodiment, methyl, ethyl, n-propyl, isopropyl, or tert-butyl; in one embodiment, methyl, ethyl, n-propyl, isopropyl, or n-butyl; in one embodiment, methyl, ethyl, or n-propyl; in one embodiment, methyl or n-propyl; in one embodiment, methyl, ethyl, or n-propyl; in one embodiment, methyl, ethyl, or n-propyl. Similarly, "C 1-3 The term "alkyl" refers to a straight-chain or branched alkyl having 1 to 3 carbon atoms, for example, methyl, ethyl, n-propyl, or isopropyl; in one embodiment, it is methyl or ethyl; in one embodiment, it is n-propyl or isopropyl; in one embodiment, it is methyl or isopropyl; in one embodiment, it is methyl or n-propyl; in one embodiment, it is ethyl or isopropyl; in one embodiment, it is methyl, in one embodiment, it is ethyl, in one embodiment, it is isopropyl, and in one embodiment, it is n-propyl. Similarly, "C5 alkyl" refers to a straight-chain or branched alkyl having 5 carbon atoms, such as n-pentyl, 1-methylbutyl, 2-methylbutyl, 3-methylbutyl, 1,1-dimethylpropyl, 2,2-dimethylpropyl, and in one embodiment, n-pentyl. "C 3-6The term "cycloalkyl" refers to cycloalkyl having 3 to 6 carbon atoms, such as cyclopropyl, cyclobutyl, cyclopentyl, and cyclohexyl. In one embodiment, it is cyclobutyl, cyclopentyl, or cyclohexyl, in one embodiment, cyclobutyl or cyclopentyl, in one embodiment, cyclopentyl or cyclohexyl, in one embodiment, cyclopropyl or cyclobutyl, in one embodiment, cyclopropyl, in one embodiment, cyclobutyl, in one embodiment, cyclopentyl, and in one embodiment, cyclohexyl. "C 1-3 The term "alkylene" refers to the above-mentioned "C 1-3 The carbon atom of the alkyl group has another bond. Examples include methylene, ethylene, trimethylene, methylmethylene, 1,1-dimethylmethylene, etc. In one embodiment, a straight or branched C 1-3 It is alkylene, and in one embodiment, it is methylene, ethylene, or trimethylene, in one embodiment, it is methylene or ethylene, in one embodiment, it is methylene, and in one embodiment, it is ethylene. Similarly, "C 1-6 The term "alkylene" refers to the above-mentioned "C 1-6 The carbon atom of "alkyl" is a divalent group having another bond. For example, methylene, ethylene, trimethylene, methylethylene, tetramethylene, methyltrimethylene, ethylethylene, dimethylethylene, pentamethylene, hexamethylene, etc. In one embodiment, it is methylene, ethylene, trimethylene, tetramethylene, pentamethylene, hexamethylene, and in another embodiment, C 1-3 It is alkylene. Similarly, "C 1-12 The term "alkylene" refers to the above-mentioned "C 1-12 The carbon atom of the alkyl group has another bond. Examples include methylene, ethylene, trimethylene, tetramethylene, pentamethylene, hexamethylene, and dodecamethylene. In one embodiment, a straight-chain or branched C 1-12 alkylene, and in one embodiment, C 3-8It is alkylene, in one embodiment it is C5 alkylene, and in one embodiment it is pentamethylene. Similarly, "C5 alkylene" refers to a divalent group in which the carbon atom of the "C5 alkyl" has another bond. Examples include 1-methyltetramethylene, 2-methyltetramethylene, 3-methyltetramethylene, 1,1-dimethyltrimethylene, and 2,2-dimethyltrimethylene, and in one embodiment, pentamethylene. "Heterocycloalkyl" refers to a 4- to 7-membered saturated heterocyclic group containing 1 to 4 heteroatoms selected from the group consisting of oxygen, sulfur, and nitrogen as ring-constituting atoms, and may contain a partially unsaturated bond. Furthermore, the sulfur atom as a ring-constituting atom of the saturated heterocyclic group may be oxidized. One embodiment of "heterocycloalkyl" is "4- to 6-membered heterocycloalkyl containing 1 to 2 heteroatoms selected from the group consisting of oxygen, sulfur, and nitrogen as ring-constituting atoms," another embodiment is "4- to 6-membered heterocycloalkyl containing 1 to 2 oxygen atoms as ring-constituting atoms," another embodiment is "4- to 6-membered heterocycloalkyl containing one oxygen atom as ring-constituting atom," and another embodiment is "4- to 6-membered heterocycloalkyl containing 1 to 2 nitrogen atoms as ring-constituting atoms," and examples thereof include oxetanyl, tetrahydrofuranyl, tetrahydropyranyl, azetidinyl, and pyrrolidinyl. , piperidinyl, oxazolidinyl, imidazolidinyl, piperazinyl, morpholinyl, thiomorpholinyl, dioxothiomorpholinyl, in one embodiment, oxetanyl, tetrahydropyranyl, or tetrahydrofuranyl, in one embodiment, tetrahydropyranyl or tetrahydrofuranyl, in one embodiment, tetrahydropyranyl, in one embodiment, tetrahydrofuranyl, in one embodiment, azetidinyl, pyrrolidinyl, piperidinyl, or piperazinyl, in one embodiment, piperidinyl or piperazinyl, in one embodiment, piperidinyl, and in one embodiment, piperazinyl. "Heterocycloalkylene" is a divalent group among the above-mentioned "heterocycloalkyl" in which a nitrogen atom or carbon atom constituting the ring has another bond. One embodiment of "heterocycloalkylene" is "4- to 6-membered heterocycloalkylene containing 1 to 2 heteroatoms selected from the group consisting of oxygen, sulfur, and nitrogen as ring-constituting atoms", another embodiment is "4- to 6-membered heterocycloalkylene containing 1 to 2 oxygen atoms as ring-constituting atoms", another embodiment is "4- to 6-membered heterocycloalkylene containing one oxygen atom as ring-constituting atom", another embodiment is "4- to 6-membered heterocycloalkylene containing 1 to 2 nitrogen atoms as ring-constituting atoms", and another embodiment is oxetanediyl, tetrahydrofurandiyl, tetrahydropyrandiyl, azetidinediyl, pyrrolidinediyl, piperidinediyl, oxazolidinyl, benzo ... In one embodiment, the alkyl group is tetrahydropyrandiyl, imidazolidinediyl, piperazinediyl, morpholinediyl, thiomorpholinediyl, or dioxothiomorpholinediyl; in one embodiment, the alkyl group is oxetanediyl, tetrahydropyrandiyl, or tetrahydrofurandiyl; in one embodiment, the alkyl group is tetrahydropyrandiyl or tetrahydrofurandiyl; in one embodiment, the alkyl group is tetrahydropyrandiyl; in one embodiment, the alkyl group is tetrahydrofurandiyl; in one embodiment, the alkyl group is azetidinediyl, pyrrolidinediyl, piperidinediyl, or piperazinediyl; in one embodiment, piperidinediyl or piperazinediyl; in one embodiment, piperidinediyl; and in one embodiment, piperazinediyl. A "bridged heterocycloalkyl" is a 7- to 9-membered bridged heterocyclic group containing 1 or 2 nitrogen atoms as ring-constituting atoms. In one embodiment, it is a saturated 7- to 9-membered bridged heterocyclic group containing 1 or 2 nitrogen atoms as ring-constituting atoms, in another embodiment, it is a saturated 7- to 9-membered bridged heterocycloalkyl containing two nitrogen atoms as ring-constituting atoms, and in another embodiment, it is a saturated 7- to 9-membered bridged heterocycloalkyl containing two nitrogen atoms as ring-constituting atoms, one of the two nitrogen atoms being bonded to a hydrogen atom. Examples include diazabicyclo[2.2.2]octanyl, diazabicyclo[3.2.1]octanyl, diazabicyclo[3.1.1]heptanyl, diazabicyclo[2.2.1]heptanyl, and diazabicyclo[3.3.1]nonanyl. In one embodiment, the diazabicyclo[2.2.2]octanyl, diazabicyclo[3.2.1]octanyl, diazabicyclo[3.2.1]oct-6-enyl, diazabicyclo[3.2.1]oct-2-enyl, diazabicyclo[3.1.1]heptanyl, diazabicyclo[2.2.1]heptanyl, diazabicyclo[2.2.1]hept-5-enyl, and in another embodiment, the diazabicyclo[2.2.2]octanyl, diazabicyclo[3.2.1]octanyl, diazabicyclo[3.1.1]heptanyl, or diazabicyclo[2.2.1]heptanyl. In one embodiment, it is diazabicyclo[2.2.1]heptanyl or diazabicyclo[3.2.1]octanyl, in one embodiment, it is diazabicyclo[2.2.1]heptanyl, in one embodiment, it is diazabicyclo[3.2.1]octanyl, in one embodiment, it is 2,5-diazabicyclo[2.2.1]heptanyl or 3,8-diazabicyclo[3.2.1]octanyl, in one embodiment, it is 2,5-diazabicyclo[2.2.1]heptanyl, and in one embodiment, it is 3,8-diazabicyclo[3.2.1]octanyl. A "bridged heterocycloalkylene" is a divalent group among the above-mentioned "bridged heterocycloalkyls" in which a nitrogen atom or carbon atom constituting the ring has another bond. In one embodiment, it is a saturated 7- to 9-membered bridged heterocycloalkylene containing two nitrogen atoms, and in another embodiment, it is a saturated 7- to 9-membered bridged heterocycloalkylene containing two nitrogen atoms, one of the two nitrogen atoms being bonded to a hydrogen atom. Examples include diazabicyclo[2.2.2]octanediyl, diazabicyclo[3.2.1]octanediyl, diazabicyclo[3.1.1]heptanediyl, diazabicyclo[2.2.1]heptanediyl, and diazabicyclo[3.3.1]nonanediyl. In one embodiment, the diazabicyclo[2.2.2]octanediyl is diazabicyclo[3.2.1]octanediyl, diazabicyclo[3.2.1]oct-6-enediyl, diazabicyclo[3.2.1]oct-2-enediyl, diazabicyclo[3.1.1]heptanediyl, diazabicyclo[2.2.1]heptanediyl, or diazabicyclo[2.2.1]hept-5-enediyl. In another embodiment, the diazabicyclo[2.2.2]octanediyl is diazabicyclo[3.2.1]octanediyl, diazabicyclo[3.1.1]heptanediyl, or diazabicyclo[2.2.1]heptanediyl. In one embodiment, it is diazabicyclo[2.2.1]heptanediyl or diazabicyclo[3.2.1]octanediyl, in one embodiment, diazabicyclo[2.2.1]heptanediyl, in one embodiment, diazabicyclo[3.2.1]octanediyl, in one embodiment, 2,5-diazabicyclo[2.2.1]heptanediyl or 3,8-diazabicyclo[3.2.1]octanediyl, in one embodiment, 2,5-diazabicyclo[2.2.1]heptanediyl, and in one embodiment, 3,8-diazabicyclo[3.2.1]octanediyl. A "bridged piperazinyl" is a piperazinyl having a bridge structure between carbon atoms on the ring, and the bridge structure is composed of carbon atoms. For example, it is diazabicyclo[2.2.1]heptanyl, diazabicyclo[3.2.1]octanyl, or diazabicyclo[3.1.1]heptanyl. In one embodiment, it is diazabicyclo[2.2.1]heptanyl. In one embodiment, it is diazabicyclo[3.2.1]octanyl. In one embodiment, it is diazabicyclo[3.1.1]heptanyl, in one embodiment, 2,5-diazabicyclo[2.2.1]heptanyl, or 3,8-diazabicyclo[3.2.1]octanyl, in one embodiment, 2,5-diazabicyclo[2.2.1]heptanyl, or 3,8-diazabicyclo[3.2.1]octanyl. A "bridged piperazinediyl" is a divalent group in which the nitrogen atom constituting the ring of the "bridged piperazinyl" has another bond. Examples include diazabicyclo[2.2.1]heptanediyl, diazabicyclo[3.2.1]octanediyl, and diazabicyclo[3.1.1]heptanediyl. In one embodiment, it is diazabicyclo[2.2.1]heptanediyl. In another embodiment, it is diazabicyclo[3.2.1]octanediyl. In one embodiment, it is diazabicyclo[3.1.1]heptanediyl, in another embodiment, it is 2,5-diazabicyclo[2.2.1]heptanediyl or 3,8-diazabicyclo[3.2.1]octanediyl, in another embodiment, it is 2,5-diazabicyclo[2.2.1]heptanediyl, or in another embodiment, it is 3,8-diazabicyclo[3.2.1]octanediyl. "Spiroheterocycloalkyl" refers to a saturated 7- to 9-membered heterocyclocyclic group containing one or two nitrogen atoms as ring-constituting atoms and a spiro atom. In one embodiment, it is a saturated 7- to 9-membered heterocyclocyclic group containing two nitrogen atoms as ring-constituting atoms and a spiro atom. Examples include diazaspiro[3.3]heptanyl, diazaspiro[3.4]octanyl, diazaspiro[3.5]nonanyl, and diazaspiro[4.4]nonanyl. In one embodiment, it is 2,6-diazaspiro[3.4]octanyl, and in another embodiment, it is 2,6-diazaspiro[3.3]heptanyl. "Spiroheterocycloalkylene" refers to a divalent group among the "spiroheterocycloalkyls" described above, which has two nitrogen atoms as ring-constituting atoms, and each of the two nitrogen atoms has a bond. Examples include 2,6-diazaspiro[3.3]heptanediyl, 2,6-diazaspiro[3.4]octanediyl, 2,7-diazaspiro[3.5]nonanediyl, and 2,7-diazaspiro[4.4]nonanediyl. In one embodiment, it is 2,6-diazaspiro[3.4]octanediyl, and in another embodiment, it is 2,6-diazaspiro[3.3]heptanediyl. Furthermore, "spiroheterocycloalkylene" may be a divalent group among the "spiroheterocycloalkyls" described above, where a nitrogen atom or carbon atom constituting the ring has an additional bond. That is, one embodiment of "spiroheterocycloalkylene" is a saturated 7- to 9-membered spiroheterocycloalkylene containing 1 or 2 nitrogen atoms, such as 2,6-diazaspiro[3.3]heptanediyl, 2,6-diazaspiro[3.4]octanediyl, 2,7-diazaspiro[3.5]nonanediyl, 2,7-diazaspiro[4.4]nonanediyl, 2-azaspiro[3.3]heptanediyl, 2-azaspiro[3.4]octanediyl, 6-azaspiro[3.4]octanediyl, 2-azaspiro[3.5]nonanediyl, 7-azaspiro[3.5]nonanediyl, 2-azaspiro[4.4]nonanediyl, and 7-azaspiro[4.4]nonanediyl. In one embodiment, it is 2,6-diazaspiro[3.4]octanediyl, and in another embodiment, it is 2,6-diazaspiro[3.3]heptanediyl. The term "heterocycle" refers to an aromatic heterocycle containing 1 to 4 heteroatoms selected from the group consisting of oxygen, sulfur, and nitrogen as ring-constituting atoms. The "five-membered heterocycle" is a five-membered heterocycle containing 1 to 4 heteroatoms selected from the group consisting of oxygen, sulfur, and nitrogen as ring-constituting atoms. One embodiment of the "five-membered heterocycle" is a pyrazole ring, imidazole ring, triazole ring, tetrazole ring, oxazole ring, isoxazole ring, thiazole ring, isothiazole ring, oxadiazole ring, or thiadiazole ring, and another embodiment is a pyrazole ring, imidazole ring, triazole ring, oxazole ring, isoxazole ring, thiazole ring, isothiazole ring, oxadiazole ring, or thiadiazole ring. The "6-membered heterocycle" is a 6-membered heterocycle containing 1 to 3 nitrogen atoms as ring-constituting atoms. One embodiment of the "6-membered heterocycle" is a 6-membered heterocycle containing 1 to 3 nitrogen atoms as ring-constituting atoms, and one embodiment is a pyridine ring, a pyrimidine ring, a pyrazine ring, a pyridazine ring, or a triazine ring. The "5-membered to 6-membered heterocycle" is a 5-membered heterocycle or a 6-membered heterocycle. In one embodiment, the "5-membered to 6-membered heterocycle" is a 5-membered heterocycle, and in another embodiment, a 6-membered heterocycle. "Heteroaryl" refers to a 5- or 6-membered aromatic heterocyclic group containing 1 to 4 heteroatoms selected from the group consisting of oxygen, sulfur, and nitrogen as ring-constituting atoms. In one embodiment, it is a 5-membered heteroaryl containing 1 to 4 heteroatoms selected from the group consisting of oxygen, sulfur, and nitrogen as ring-constituting atoms, or a 6-membered heteroaryl containing 1 to 3 nitrogen atoms as ring-constituting atoms, in another embodiment, a 5-membered heteroaryl containing 1 to 4 heteroatoms selected from the group consisting of oxygen, sulfur, and nitrogen as ring-constituting atoms, in another embodiment, a 6-membered heteroaryl containing 1 to 3 nitrogen atoms as ring-constituting atoms, and in another embodiment, pyrazolyl, imidazolyl, and pyridyl, pyrimidinyl, pyrazinyl, pyridazinyl, or triazinyl, and in one embodiment, pyrazolyl, imidazolyl, triazolyl, tetrazolyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, oxadiazolyl, or thiadiazolyl, and in another embodiment, pyridyl, pyrimidinyl, pyrazinyl, pyridazinyl, or triazinyl. "Heteroarylene" is a divalent group among the above-mentioned "heteroaryl" in which two different carbon and / or nitrogen atoms constituting the ring have bonds. One embodiment of "heteroarylene" is a 5-membered heteroarylene containing 1 to 4 heteroatoms selected from the group consisting of oxygen, sulfur, and nitrogen as ring-constituting atoms, or a 6-membered heteroarylene containing 1 to 3 nitrogen atoms as ring-constituting atoms, another embodiment is a 5-membered heteroarylene containing 1 to 4 heteroatoms selected from the group consisting of oxygen, sulfur, and nitrogen as ring-constituting atoms, another embodiment is a 6-membered heteroarylene containing 1 to 3 nitrogen atoms as ring-constituting atoms, and another embodiment is pyrazolediyl, imidazolediyl, triazolediyl, tetrazolediyl, oxazolidinyl, benzo ...

[0039] In one embodiment, the aryl group is pyrazolediyl, imidazolediyl, triazolediyl, tetrazolediyl, oxazolediyl, isoxazolediyl, thiazoldiyl, isothiazolediyl, oxadiazolediyl, thiazoldiyl, isothiazolediyl, oxadiazolediyl, thiazoldiyl, or thiadiazolediyl. In another embodiment, the aryl group is pyridinediyl, pyrimidinediyl, pyrazinediyl, pyridazinediyl, or triazinediyl. The "4- to 8-membered saturated heterocycle" refers to a 4- to 8-membered saturated heterocycle containing 1 or 2 heteroatoms selected from the group consisting of oxygen, sulfur, and nitrogen as ring-constituting atoms, and may contain a partially unsaturated bond, may have a bridge, or may form a spiro ring. Furthermore, the sulfur atom contained in the heterocycle may be oxidized. Some embodiments include oxetane, tetrahydrofuran, tetrahydropyran, azetidine, pyrrolidine, piperidine, azepane, oxazolidine, imidazolidine, piperazine, morpholine, thiomorpholine, dioxothiomorpholine, azabicyclo[2.2.1]heptane, diazabicyclo[2.2.1]heptane, azaspiro[3.3]heptane, azaspiro[3.4]octane, oxazaspiro[3.3]heptane, or diazaspiro[3.3]heptane. Some embodiments include oxetane, tetrahydrofuran, The compound is tetrahydropyran, azetidine, pyrrolidine, piperidine, piperazine, morpholine, thiomorpholine, dioxothiomorpholine, azaspiro[3.3]heptane, or oxazaspiro[3.3]heptane; in one embodiment, the compound is azetidine, tetrahydropyran, morpholine, or oxazaspiro[3.3]heptane; in one embodiment, the compound is azetidine or tetrahydropyran; in one embodiment, the compound is morpholine or oxazaspiro[3.3]heptane; and in one embodiment, the compound is tetrahydropyran. "Optionally substituted heterocycloalkyl", "optionally substituted heterocycloalkylene", and L P , L 1A , L 4A "Optionally substituted C" included in 1-６ One embodiment of the permissible substituents for "alkylene" is C 1-3 Alkyl, -O(C 1-3 alkyl), C=O, halogen, OH, and in one embodiment, C 1-3 Alkyl, -O(C 1-3 alkyl), halogen, and in one embodiment, —O(C 1-3 alkyl), halogen, and in one embodiment, C 1-3It is alkyl, in one embodiment it is OH, in one embodiment it is F, in one embodiment it is methyl, and in one embodiment it is ethyl. "Optionally substituted C 1-６ Alkyl, optionally substituted C 1-３ Alkyl, optionally substituted C 1-３ One embodiment of the permissible substituents for "alkylene" is C 1-3 Alkyl, -O(C 1-3 alkyl), C=O, halogen, OH, and in one embodiment, C 1-3 Alkyl, -O(C 1-3 alkyl), halogen, and in one embodiment, —O(C 1-3 alkyl), halogen, and in one embodiment, C 1-3 It is alkyl, in one embodiment it is OH, in one embodiment it is F, in one embodiment it is methyl, and in one embodiment it is ethyl. Some embodiments of the permissible substituents for "optionally substituted heteroarylene", "optionally substituted phenylene", and "optionally substituted heteroaryl" include C 1-3 Alkyl, -O(C 1-3 alkyl), halogen, OH, and in one embodiment, C 1-3 Alkyl, -O(C 1-3 alkyl), halogen, and in one embodiment, C 1-3 In one embodiment, it is alkyl, in one embodiment, it is methyl, in one embodiment, it is ethyl, in one embodiment, it is halogen, and in one embodiment, it is F. Some embodiments of the substituents permitted in the "optionally substituted oxazolyl" include C 1-3 It is alkyl, and in one embodiment, it is methyl or isopropyl, and in one embodiment, it is methyl, and in one embodiment, it is isopropyl. "Optionally substituted C 1-12 alkylene”, and R st1 "Optionally substituted C" included in 1-6 Some embodiments of the permissible substituents for "alkylene" include -NH, -C1-6 Alkylene-NH2, -NH-C(=O)-C 1-6 Alkyl, -NH-C(=O)-C 1-3 alkyl, and in one embodiment, -C 1-6 It is alkylene-NH2. "Halogen" means F, Cl, Br, and I. In one embodiment, it is F, Cl, or Br, in another embodiment, it is F or Cl, in another embodiment, it is F, in another embodiment, it is Cl, and in another embodiment, it is Br. "Halogeno C 1-6 "Alkyl" means a straight or branched C alkyl group substituted with one or more halogen atoms. 1-6 It is an alkyl group. Examples include trifluoromethyl, trifluoroethyl, trifluoropropyl, 2-fluoro-2-methylpropyl, difluoromethyl, difluoroethyl, fluoromethyl, and chloromethyl. In one embodiment, it is difluoroethyl, trifluoromethyl, or difluoromethyl, in another embodiment, it is trifluoromethyl or difluoromethyl, in yet another embodiment, it is trifluoromethyl, and in another embodiment, it is difluoromethyl. "EUB" refers to a group capable of binding to an E3 ubiquitin ligase. In one embodiment, the group is capable of binding to an E3 ubiquitin ligase selected from the group consisting of VHL (von Hippel-Lindau), cereblon, IAP (inhibitor of apoptosis protein), MDM2 (mouse double minute 2 homolog), DCAF11 (DDB1 and CUL4 associated factor 11), DCAF15 (DDB1 and CUL4 associated factor 15), DCAF16 (DDB1 and CUL4 associated factor 16), BIRC2 (baculoviral IAP repeat containing 2), KEAP1 (Kelch-like ECH-associated protein 1), RNF4 (RING finger protein 4), RNF114 (RING finger protein 114), FEM1B (protein fem-1 homolog B), and AhR (aryl hydrocarbon receptor). In one embodiment, the group is capable of binding to one E3 ubiquitin ligase selected from the group consisting of VHL, cereblon, IAP, and MDM2. In one embodiment, the group is capable of binding to one E3 ubiquitin ligase selected from the group consisting of VHL and cereblon. In one embodiment, the group is capable of binding to VHL. In one embodiment, the group is capable of binding to cereblon. Those skilled in the art can understand this by referring to the following documents, but the present invention is not limited to these. [Literature] Current Research in Chemical Biology., 2022, 2, 100020 Front. Chem., 2021, 9, 707317 J. Am. Chem. Soc., 2021, 143, 5141 Signal Transduct. Target. Ther., 2020, 5, 129 Nat. Chem. Biol., 2019, 15(7), 737 Communications Biology., 2020, 3, 140 Sci. Rep., 2020, 10(1), 15543 ACS Chem. Biol., 2019, 14, 2430 Cell Chem. Biol., 2021, 28(4), 559 J. Am. Chem. Soc., 2022, 144, 701 ACS Chem. Biol., 2019, 14, 2822 The term "G12D mutation" refers to a mutation in which the amino acid residue corresponding to codon 12 in the wild-type protein is converted from glycine to aspartic acid. "G12D mutant KRAS" refers to KRAS having the above-mentioned "G12D mutation." "Z Ｎ１ " is the following formula (Z N1 -1) to (Z N1 -15) ( ＊ＬＧＺ is LG Z or L P indicates the bond with R Z1’ are, independently of each other, optionally substituted C 1-6 Alkyl, halogen, cyano, -OH, -O-(optionally substituted C 1-6 alkyl), -S-(optionally substituted C 1-6 alkyl), -NH-(optionally substituted C 1-6 alkyl) or -N-(optionally substituted C 1-6 alkyl)2, n' is an integer from 0 to 2, and R Z2’ , R Z3’ and R Z４’ are each independently H or optionally substituted C 1-6 alkyl, and ring B1′ is a benzene ring or a 6-membered heterocycle, wherein R Z1’ and- ＊ＬＧZ forms a bond with the carbon atom constituting ring B1'. "Z Ｎ２ " is the following formula (Z N2 -1) to (Z N2 -15) ( ＊ＬＧＺ is LG Z or L P indicates the bond with R Z1’ are, independently of each other, optionally substituted C 1-6 Alkyl, halogen, cyano, -OH, -O-(optionally substituted C 1-6 alkyl), -S-(optionally substituted C 1-6 alkyl), -NH-(optionally substituted C 1-6 alkyl) or -N-(optionally substituted C 1-6 alkyl)2, n' is an integer from 0 to 2, and R Z2’ and R Z3’ are each independently H or optionally substituted C 1-6 alkyl, and ring B1′ is a benzene ring or a 6-membered heterocycle, wherein R Z1’ and- ＊ＬＧZ forms a bond with the carbon atom constituting ring B1'. "Z Ｃ " is the following formula (Z C -16) to (Z C -27) ( ＊ＬＧＺ is LG Z or L P indicates the bond with R Z1’ are, independently of each other, optionally substituted C 1-6 Alkyl, halogen, cyano, -OH, -O-(optionally substituted C 1-6 alkyl), -S-(optionally substituted C 1-6 alkyl), -NH-(optionally substituted C 1-6 alkyl) or -N-(optionally substituted C 1-6 alkyl)2, n' is an integer from 0 to 2, and R Z2’ , R Z4’ and R Z５’ are each independently H or optionally substituted C 1-6alkyl, and M' is a bond, -O-, -S-, -N(R M’ )- or optionally substituted C 1-３ alkylene, and R M’ is H or optionally substituted C 1-３ alkyl, ring B1′ is a benzene ring or a 6-membered heterocycle, and ring B2′ is a benzene ring or a 5- to 6-membered heterocycle, wherein R Z1’ and- ＊ＬＧZ forms a bond with the carbon atom constituting ring B1', and M', R Z1’ and- ＊ＬＧZ forms a bond with the carbon atom constituting ring B2'. The term "antigen" is used to refer to a molecule or a portion of a molecule to which an antigen-binding protein, such as an antibody or an antigen-binding fragment, can specifically bind. An antigen can be a protein, a nucleic acid, or other molecule. An antigen may have one or more epitopes that can interact with different antibodies, etc. Antibodies (or immunoglobulins) are glycoproteins with a basic structure consisting of a four-chain structure with a symmetric Y-shape, consisting of two heavy chains with a single sequence and two light chains with a single sequence. There are five classes of antibodies: IgG, IgM, IgA, IgD, and IgE. Heavy chains typically consist of polypeptide chains containing approximately 440 amino acids and have characteristic structures for each class. These are called Igγ, Igμ, Igα, Igδ, and Igε for IgG, IgM, IgA, IgD, and IgE, respectively. IgG subclasses include IgG1, IgG3, IgG4, and IgG4, with corresponding heavy chains called Igγ1, Igγ2, Igγ3, and Igγ4. Light chains typically consist of polypeptide chains containing approximately 220 amino acids. Two types, lambda and kappa, are known: Igλ and Igκ. The two types of light chains can pair with either type of heavy chain. Antibody molecules have four intrachain disulfide bonds in heavy chains (five in Igμ and Igε) and two in light chains, forming a loop every 100–110 amino acid residues. The three-dimensional structures of these disulfide bonds are similar between each loop and are called structural units or domains. The domain located at the N-terminus of both heavy and light chains is called the variable region. It has diverse amino acid sequences even among antibodies of the same class (or subclass) from the same animal species, and is known to be involved in the specificity of antibody-antigen binding. The amino acid sequence of the C-terminal domain downstream of the variable region is nearly constant for each class or subclass and is called the constant region. From the N-terminus to the C-terminus, the heavy chain contains a heavy chain variable region (VH) and a heavy chain constant region (CH). The CH is further divided into three domains from the N-terminus: CH1, CH2, and CH3. From the N-terminus to the C-terminus, the light chain contains a light chain variable region (VL) and a light chain constant region (CL). The amino acid sequences of the three complementarity-determining regions (CDRs) present in VH and VL vary greatly, contributing to the variability of the variable regions. CDRs are regions consisting of approximately 5 to 10 amino acid residues and are located at the N-terminus of the heavy and light chains, in the order CDR1, CDR2, and CDR3, respectively, and form the antigen-binding site. On the other hand, the parts of the variable regions other than the CDRs are called framework regions (FRs), which consist of FR1 to FR4 and show relatively little variation in amino acid sequence. When an antibody is treated with the protease papain, three antibody fragments are obtained: the two N-terminal fragments are called Fab (Fragment, antigen binding) regions, and the C-terminal fragment is called Fc (Fragment, crystallizable) region. As used herein, the term "antibody" refers to a polypeptide that specifically binds to an antigen and may have any structure as long as it is capable of specifically binding to the antigen. For example, antibodies include polypeptides with a four-chain structure as a basic structure, such as IgG, as well as various polypeptide forms, such as antigen-binding fragments and multispecific antibodies (e.g., bispecific antibodies), which will be described below. An "antigen-binding fragment" is a molecule containing at least one polypeptide chain that has antigen-binding activity derived from an antibody. Representative antigen-binding fragments include single-chain variable region fragments (scFv), Fab fragments, Fab' fragments, and F(ab')2 fragments. scFv is a monovalent antigen-binding fragment consisting of a VH and VL linked by a linker. Fab fragments are monovalent antigen-binding fragments consisting of a light chain and a fragment containing the VH and CH1 domains of the heavy chain. Fab' fragments are monovalent antigen-binding fragments consisting of a fragment containing the light chain, the VH and CH1 domains of the heavy chain, and part of the hinge region, and this hinge region contains cysteine ​​residues that formed the inter-heavy chain disulfide bonds. F(ab')2 fragments are bivalent molecules in which Fab' fragments are linked by disulfide bonds. "Monovalent" means that they contain one antigen-binding site, and "bivalent" means that they contain two antigen-binding sites. The term "polypeptide" refers to a structure in which multiple amino acids are linked by peptide bonds. The amino acids used in a polypeptide may be either natural amino acids or artificial amino acids. The number of amino acid residues contained in a polypeptide may be two or more, and preferably ten or more. A "multispecific antibody" is an antibody that can specifically bind to two or more different antigens, and is called, for example, a bispecific antibody or a trispecific antibody depending on the number of antigens to which it binds. Multispecific antibodies include complexes of two or more antibodies and / or antigen-binding fragments, each capable of binding to a different antigen, and the term "antibody" as used herein includes multispecific antibodies unless otherwise limited by the context. A "human antibody" refers to an antibody having a human immunoglobulin amino acid sequence. As used herein, a "humanized antibody" refers to an antibody in which some, most, or all of the amino acid residues other than the CDRs have been substituted with amino acid residues derived from a human immunoglobulin molecule. The humanization method is not particularly limited, and humanized antibodies can be prepared by referring to, for example, U.S. Pat. No. 5,225,539 and U.S. Pat. No. 6,180,370. "Post-translational modification" refers to post-translational modification of an antibody when it is expressed in a cell. Examples of post-translational modifications include N-linked or O-linked glycosylation, N-terminal or C-terminal processing, deamidation, aspartic acid isomerization, and methionine oxidation. Such post-translational modifications are known to occur in various antibodies (J. Pharma. Sci., 2008; Vol. 97: pp. 2426-2447). The amino acid residue numbers of antibodies used herein can be specified according to the Kabat numbering system or the EU index (Kabat et al., Sequences of Proteins of Immunological Interest, 5th Ed., 1991, NIH Publication No. 91-3242) by designating them. "Identity" refers to the Identity value obtained using EMBOSS Needle (Necleic Acids Res., 2015; Vol. 43: pW580-W584) with the default parameters. The parameters are as follows: Gap Open Penalty = 10 Gap Extend Penalty = 0.5 Matrix = EBLOSUM62 End Gap Penalty = false In this specification, antibodies and antigen-binding fragments may be collectively referred to as "Ab." An "antibody-drug conjugate" is a conjugate in which an antibody and a drug are linked via a linker. The antibody can transport the drug to targeted cells or tissues. In one embodiment, the antibody-drug conjugate is a conjugate in which the antibody and the drug are linked via a linker that is cleavable in vivo. In another embodiment, the antibody-drug conjugate is a conjugate in which the antibody and the drug are linked via a non-cleavable linker. A "linker" is a divalent chemical group that connects one functional compound to another. In some embodiments, the linker is cleavable in vivo, and in other embodiments, it is a non-cleavable linker. A "linker cleavable in vivo" is a linker having a partial structure that is cleavable in vivo. A "partial structure cleavable in vivo" is a partial structure that can be cleaved by the action of an enzyme or the like in vivo. In one embodiment, it is a partial structure that can be cleaved by the action of a protease, and in another embodiment, it is a partial structure that can be cleaved by the action of cathepsin B. A "non-cleavable linker" refers to a linker that is not degraded in vivo, particularly in lysosomes, under acidic conditions or by the action of proteases. For example, C=O, C 1-6 Alkylene, C(=O)NH-C 1-6 alkylene, or polyethylene glycol. "Subject" means a human or other animal in need of such prevention or treatment. In one embodiment, the subject is a human in need of such treatment or prevention. The antibody-drug conjugate or salt thereof of the present invention, and the drug (D) and linker (L) constituting the antibody-drug conjugate or salt thereof A ) and antibody or antigen-binding fragment (Ab) embodiments are shown below. Even if a combination is not specifically described, one or more embodiments can be combined with another embodiment. That is, all embodiments can be freely combined. 1. Drugs (D) The drug (D) constituting the antibody-drug conjugate or salt thereof and the drug-linker conjugate of the present invention is a heterocyclic compound having the activity of inducing degradation of the G12D mutant KRAS protein. AThe drug (D) exerts its effect when part or all of the -OH in the molecule of drug (D) is cleaved in the tumor cell, liberating drug (D). If the -OH in the molecule of drug (D) forms a phosphate ester, the phosphate ester may be cleaved by phosphatase after uptake by tumor cells to generate a dephosphorylated form (Bioconjugate Chem., 2016; Vol. 27; pp. 2081-2088). Some embodiments of drug (D) in the present invention are shown below. (1-1) A heterocyclic compound or a salt thereof having an activity of inducing degradation of G12D mutant KRAS protein. (1-2) A heterocyclic compound having a structure represented by formula (II) or a salt thereof. (2-1) A is CR A or N and R A is H, cyano, or optionally substituted C 1-３ The heterocyclic compound or a salt thereof according to (1-2), wherein the heterocyclic compound or salt thereof is alkyl. (2-2) The heterocyclic compound or a salt thereof according to (1-2), wherein A is CH or N. (2-3) The heterocyclic compound or a salt thereof according to (1-2), wherein A is CH. (2-4) The heterocyclic compound or a salt thereof according to (1-2), wherein A is N. (3-1) Q is CR Q or N and R Q But H, halogen, C 3-６ cycloalkyl, vinyl, or optionally substituted C 1-３ The heterocyclic compound or a salt thereof according to (1-2), wherein the heterocyclic compound or salt thereof is alkyl. (3-2) Q is CR Q and R Q But C 3-６ The heterocyclic compound or a salt thereof according to (1-2), which is cycloalkyl. (3-3) Q is CR Q and R Q The heterocyclic compound or a salt thereof according to (1-2), wherein R is cyclopropyl. (4-1) The heterocyclic compound or a salt thereof according to (1-2), wherein E is CH or N. (4-2) The heterocyclic compound or a salt thereof according to (1-2), wherein E is CH. (5-1) R 1 is cyano, OH, halogen, and optionally substituted C 1-３ naphthyl optionally substituted with one or two groups selected from the group consisting of alkyl, or a group selected from the group consisting of the following formula (III), formula (IV) and formula (V): R 1a , R 1b and R 1c are each independently H, vinyl, halogen, or optionally substituted C 1-３ The heterocyclic compound or a salt thereof according to (1-2), wherein the heterocyclic compound or salt thereof is alkyl. (5-2) R 1 is the following formula (III): R 1a and R 1c However, independently of each other, C 1-３ The heterocyclic compound or a salt thereof according to (1-2), wherein the heterocyclic compound is alkyl or halogen. (5-3) R 1 is the following formula (III): R 1a is a halogen, and R 1c But C 1-3 The heterocyclic compound or salt thereof according to (1-2), wherein the heterocyclic compound is alkyl. (5-4) R 1 is the following formula (III-2): (6-1) R 2 But -V 1 -V 2 or W, V 1 is a bond, -CH2-, -O-, -S- or -N(R V1 )- and R V1 is H or optionally substituted C 1-３ is alkyl, V 2is a group selected from the group consisting of the following formula (VI) and formula (VII): W is a group selected from the group consisting of the following formulas (VIII), (IX), (X), (XI), (XII), (XIII), (XIV), (XV) and (XVI), R 2a are each independently OH, OCH3, F or optionally substituted C 1-３ alkyl, and the R 2a is bonded only to a carbon atom that is a constituent atom of a ring selected from the group consisting of an azetidine ring represented by formula (VI), a pyrrolidine ring represented by formula (VII), a piperidine ring represented by formula (VIII), and a piperazine ring represented by formula (IX), The heterocyclic compound or a salt thereof according to (1-2), wherein m is an integer of 0 to 2. (6-2) R 2 But -V 1 -V 2 or W, V 1 is a bond, -CH2-, -O-, -S- or -N(R V1 )- and R V１ But C 3-６ C optionally substituted with one group selected from the group consisting of cycloalkyl, halogen, and —OH 1-３ is alkyl, V 2 is a group selected from the group consisting of the following formula (VI-2) or (VII-2): The heterocyclic compound or a salt thereof according to (1-2), wherein W is a group selected from the group consisting of the following formulas (VIII-2), (IX-2), (X), (XI), (XII), (XIII), (XIV), (XV), and (XVI): (6-3) R 2 But -V 1 -V 2 or W, V 1 is a bond, -O- or -N(R V１)- and R V１ But C 1-3 is alkyl, V 2 is the following formula (VII-2), The heterocyclic compound or salt thereof according to (1-2), wherein W is the following formula (XIV): (6-4) R 2 But -V 1 -V 2 or W, V 1 is —O— or —N(CH3)—, V 2 is the following formula (VII-2), The heterocyclic compound or salt thereof according to (1-2), wherein W is the following formula (XIV): (6-5) R 2 But -V 1 -V 2 or W, V 1 is -O-, V 2 is the following formula (VII-2), The heterocyclic compound or salt thereof according to (1-2), wherein W is the following formula (XIV): (6-6) R 2 But -V 1 -V 2 or W, V 1 is -N(CH3)-, V 2 is the following formula (VII-2), The heterocyclic compound or salt thereof according to (1-2), wherein W is the following formula (XIV): (6-7) R 2 But -V 1 -V 2 or W, V 1 is a bond, -CH2-, -O-, -S- or -N(R V1)- and R V１ But C 3-６ C optionally substituted with one group selected from the group consisting of cycloalkyl, halogen, and —OH 1-３ is alkyl, V 2 is represented by the following formula (VI-2) or (VII-2), The heterocyclic compound or salt thereof according to (1-2), wherein W is a group selected from the group consisting of the following formulae (IX-2), (XIII) and (XIV): (6-8) R 2 But -V 1 -V 2 or W, V 1 is -O- or -N(R V1 )- and R V１ But C 1-３ is alkyl, V 2 is represented by the following formula (VI-2) or (VII-2), The heterocyclic compound or salt thereof according to (1-2), wherein W is a group selected from the group consisting of the following formulae (IX-2), (XIII) and (XIV): (6-9) R 2 But -V 1 -V 2 or W, V 1 is —O— or —N(CH3)—, V 2 is the following formula (VII-2), The heterocyclic compound or salt thereof according to (1-2), wherein W is the following formula (IX-2) or (XIV): (6-10) R 2 But -V 1 -V 2 or W, V 1 is a bond, -CH2-, -O-, -S- or -N(R V1 )- and R V1 is H or optionally substituted C 1-３ is alkyl, V 2 is a group selected from the group consisting of the following formula (VI) and formula (VII): W is a group selected from the following formula (VIII), formula (IX), or a 7- to 9-membered bridged heterocycloalkyl containing 1 to 2 nitrogen atoms, R 2a are each independently OH, OCH3, F or optionally substituted C 1-３ alkyl, and the R 2a is bonded only to a carbon atom that is a constituent atom of a ring selected from the group consisting of an azetidine ring represented by formula (VI), a pyrrolidine ring represented by formula (VII), a piperidine ring represented by formula (VIII), and a piperazine ring represented by formula (IX), The heterocyclic compound or a salt thereof according to (1-2), wherein m is an integer of 0 to 2. (6-11) R 2 But -V 1 -V 2 or W, V 1 is a bond, -CH2-, -O-, -S- or -N(R V1 )- and R V1 is H or optionally substituted C 1-３ is alkyl, V 2 is a group selected from the group consisting of the following formula (VI) and formula (VII): W is a group selected from the group consisting of the following formulas (VIII), (IX), (X), (XI), (XII-2), (XIII), (XIV), (XV) and (XVI), R 2a are each independently OH, OCH3, F or optionally substituted C 1-３ alkyl, and the R 2ais bonded only to a carbon atom that is a constituent atom of a ring selected from the group consisting of an azetidine ring represented by formula (VI), a pyrrolidine ring represented by formula (VII), a piperidine ring represented by formula (VIII), and a piperazine ring represented by formula (IX), The heterocyclic compound or a salt thereof according to (1-2), wherein m is an integer of 0 to 2. (6-12) R 2 But -V 1 -V 2 or W, V 1 is a bond, -CH2-, -O-, -S- or -N(R V1 )- and R V１ But C 3-６ C optionally substituted with one group selected from the group consisting of cycloalkyl, halogen, and —OH 1-３ is alkyl, V 2 is a group selected from the group consisting of the following formula (VI-2) or (VII-2): The heterocyclic compound or a salt thereof according to (1-2), wherein W is a group selected from the group consisting of the following formulas (VIII-2), (IX-2), (X), (XI), (XII-2), (XIII), (XIV), (XV), and (XVI): (6-13) R 2 is a 7- to 9-membered bridged heterocycloalkyl containing 1 or 2 nitrogen atoms, or a salt thereof, according to (1-2). (7-1) R 3 may be substituted C 1-6 The heterocyclic compound or a salt thereof according to (1-2), wherein the heterocyclic compound is alkyl, an optionally substituted heterocycloalkyl, or an optionally substituted heteroaryl. (7-2) R 3 But -O-(C 1-6 alkyl), -S-(C 1-6 alkyl), -N-(C 1-6 C optionally substituted with one group selected from the group consisting of alkyl)2 and heterocycloalkyl 1-6The heterocyclic compound or a salt thereof according to (1-2), wherein the heterocyclic compound is alkyl or an optionally substituted heterocycloalkyl. (7-3) R 3 But -O(C 1-6 C optionally substituted with one group selected from the group consisting of alkyl, oxetanyl, tetrahydrofuranyl, and tetrahydropyranyl 1-6 The heterocyclic compound or a salt thereof according to (1-2), which is alkyl, oxetanyl, tetrahydrofuranyl, or tetrahydropyranyl. (7-4) R 3 is tetrahydrofuranyl, tetrahydropyranyl, or —OCH ３ or C optionally substituted with tetrahydrofuranyl 1-3 The heterocyclic compound or a salt thereof according to (1-2), wherein the heterocyclic compound or salt thereof is alkyl. (7-5) R 3 But, -OCH ３ The heterocyclic compound or a salt thereof according to (1-2), wherein R is n-propyl, optionally substituted with R, or tetrahydropyranyl. (8-1) X is a bond, -CH2-, -O-, -S-, or -NR 4X - and R 4X is H or optionally substituted C 1-３ The heterocyclic compound or a salt thereof according to (1-2), wherein the heterocyclic compound or salt thereof is alkyl. (8-2) X is -O- or -NR 4X - and R 4X But C 1-３ The heterocyclic compound or a salt thereof according to (1-2), wherein the heterocyclic compound or salt thereof is alkyl. (8-3) The heterocyclic compound or a salt thereof according to (1-2), wherein X is —O—. (9-1) Y 1 is -O-(optionally substituted C 1-３ alkylene)- ＊Y2 , -S-(optionally substituted C 1-３ alkylene)- ＊Y2 , -SO2-(optionally substituted C 1-３ alkylene)- ＊Y2 , -NR Y -(optionally substituted C 1-３alkylene)- ＊Y2 , -(optionally substituted C 1-３ alkylene)-O- ＊Y2 , -(optionally substituted C 1-３ Alkylene)-S- ＊Y2 , -(optionally substituted C 1-３ Alkylene)-SO2- ＊Y2 or -(optionally substituted C 1-３ (Alkylene)-NR Y - ＊Y2 And ( ＊Y2 is Y 2 ) R Y is H or optionally substituted C 1-３ The heterocyclic compound or a salt thereof according to (1-2), wherein the heterocyclic compound or salt thereof is alkyl. (9-2) Y 1 But -O-(C 1-３ alkylene)- ＊Y2 Or -(C 1-３ alkylene)-O- ＊Y2 ( ＊Y2 is Y 2 and (1-2) a heterocyclic compound or a salt thereof, wherein (9-3) Y 1 But -O-(C 1-3 alkylene)- ＊Y2 ( ＊Y2 is Y 2 and (1-2) a heterocyclic compound or a salt thereof, wherein (9-4) Y 1 But -O-(methylene)- ＊Y2 ( ＊Y2 is Y 2 and (1-2) a heterocyclic compound or a salt thereof, wherein (10-1) Y 2 is a bond, an optionally substituted phenylene, or an optionally substituted heteroarylene, or a salt thereof. (10-2) Y 2 is phenylene or pyridinediyl, or a salt thereof according to (1-2). (10-3) Y 2is phenylene optionally substituted with fluorine, or a salt thereof according to (1-2). (10-4) Y 2 is phenylene, or a salt thereof according to (1-2). (10-5) Y 2 is optionally substituted phenylene or pyridinediyl, or a salt thereof according to (1-2). (11-1) L P But, Y 2 and EUB are groups that chemically bond the heterocyclic compound or salt thereof according to (1-2). (11-2) L P But, -(L 1 -L 2 -L 3 -L 4 )- and L 1 , L 2 , L 3 and L 4 are, independently of each other, bonds, C=O, -O-, -S-, -SO2-, -NR L -, acetylene-1,2-diyl, optionally substituted heterocycloalkylene, optionally substituted heteroarylene, saturated 7- to 9-membered spiroheterocycloalkylene containing 1 to 2 nitrogen atoms, saturated 7- to 9-membered bridged heterocycloalkylene containing 2 nitrogen atoms, and optionally substituted C 1-６ is a group selected from the group consisting of alkylene; R L But H or C 1-６ The heterocyclic compound or a salt thereof according to (1-2), wherein the heterocyclic compound or salt thereof is alkyl. (11-3) L P But, -(L 1 -L 2 -L 3 -L 4 )- and L 1 is C=O, L 2 But C 1-3 Piperidinediyl optionally substituted with alkyl, C 1-3Piperazinediyl optionally substituted with alkyl, C 1-3 pyrrolidinediyl, bridged piperazinediyl or 2,6-diazaspiro[3.4]octanediyl, which may be substituted by alkyl; L 3 is the bond, -N(R L3 )-, C 1-3 alkylene or piperazinediyl, L 4 is the bond, -N(R L4 )-, -O-, piperazinediyl or C 1-3 is alkylene, R L3 But H or C 1-3 is alkyl, R L4 But H or C 1-3 The heterocyclic compound or a salt thereof according to (1-2), wherein the heterocyclic compound or salt thereof is alkyl. (11-4) L P is a group selected from the group consisting of the following formulae (L-1), (L-2), (L-3), (L-4), (L-5), (L-6) and (L-7), Here, C═O in the formulas (L-1), (L-2), (L-3), (L-4), (L-5), (L-6) and (L-7) is Y 2 It forms a bond with L' is -O-, -(C 1-3 alkylene)-NH-, -N(CH3)(C 1-3 alkylene)-, piperazinediyl or -(C 1-3 alkylene)-piperazinediyl, L'' is a bond, C 1-3 Alkylene, or -(C 1-3 alkylene)-O-; R L2 But H or C 1-3 The heterocyclic compound or a salt thereof according to (1-2), wherein the heterocyclic compound or salt thereof is alkyl. (11-5) L P is a group selected from the group consisting of the following formulae (L-1), (L-2), (L-3), (L-4), (L-5) and (L-7), Here, C═O in the formulas (L-1), (L-2), (L-3), (L-4), (L-5) and (L-7) is Y 2 It forms a bond with L' is -O-, -(C 1-3 alkylene)-NH-, -N(CH3)(C 1-3 alkylene)-, piperazinediyl or -(C 1-3 alkylene)-piperazinediyl, L'' is a bond, C 1-3 Alkylene, or -(C 1-3 alkylene)-O-; R L2 But H or C 1-3 The heterocyclic compound or a salt thereof according to (1-2), wherein the heterocyclic compound or salt thereof is alkyl. (11-6) L P is represented by the following formula (L-5A) or (L-7A), wherein C=O in the formulas (L-5A) and (L-7A) is Y 2 The heterocyclic compound or salt thereof according to (1-2), wherein (11-7) L P is formula (L-5A), and C=O in the formula (L-5A) is Y 2 The heterocyclic compound or salt thereof according to (1-2), wherein (11-8) L P But -L V -J-, L V But, -(L 5 -L 6 -L 7 -L 8 )- and L 5 , L 6 , L 7 , L 8 are, independently of each other, a bond, -O-, or -NR L5 -, optionally substituted pyrrolidinediyl, optionally substituted piperidinediyl, optionally substituted piperazinediyl, optionally substituted C 1-3 a group selected from the group consisting of alkylene and C═O; R L5 But H or C 1-3 is alkyl, The heterocyclic compound or a salt thereof according to (1-2), wherein J is NH or a 5-membered heteroarylene containing 1 to 4 heteroatoms selected from the group consisting of oxygen, sulfur, and nitrogen. (12-1) L V But, -(L 5 -L 6 -L 7 -L 8 )- and L 5 , L 6 , L 7 , L 8 are, independently of each other, a bond, -O-, or -NR L5 -, optionally substituted pyrrolidinediyl, optionally substituted piperidinediyl, optionally substituted piperazinediyl, optionally substituted C 1-3 a group selected from the group consisting of alkylene and C═O; R L5 But H or C 1-3 The heterocyclic compound or a salt thereof according to (11-8), wherein the heterocyclic compound is alkyl. (12-2) L V But, bond, C 1-3 alkylene, C═O, or a group selected from the group consisting of the following formulae (L-10), (L-11), (L-12), (L-13), (L-14), and (L-15) (wherein *Y2 is Y 2 (showing the bond with R L5 But H or C 1-3 is alkyl, R L6 , R L7 are each independently H, F, OH, OCH3 or optionally substituted C 1-3 is alkyl, R L is CH or N, The heterocyclic compound or a salt thereof according to (11-8), wherein k is an integer of 1 to 2. (12-3) L Vis a bond, or a salt thereof according to (11-8). (13-1) The heterocyclic compound or a salt thereof according to (11-8), wherein J is NH or a 5-membered heteroarylene containing 1 to 4 heteroatoms selected from the group consisting of oxygen, sulfur, and nitrogen. (13-2) J is NH or a group selected from the group consisting of the following formulae (L-16), (L-17), (L-18) and (L-19) (wherein: *LV L V and (11-8) or a salt thereof. (13-3) J is the following formula (L-17) (wherein: *LV L V and (11-8) or a salt thereof. (14-1)-Y 2 -L V -J is represented by the following formula (L-20): *Y1 is Y 1 is -O-CH2-, then Y 2 -L V -J represents a bond to the carbon atom of the -O-CH2-.), (11-8) The heterocyclic compound or a salt thereof according to (11-8). (15-1) The heterocyclic compound or salt thereof according to (1-2), wherein EUB is a group capable of binding to one E3 ubiquitin ligase selected from the group consisting of VHL, cereblon, IAP, MDM2, DCAF11, DCAF15, DCAF16, BIRC2, KEAP1, RNF4, RNF114, FEM1B, and AhR. (15-2) The heterocyclic compound or salt thereof according to (1-2), wherein EUB is a group capable of binding to an E3 ubiquitin ligase selected from the group consisting of VHL and cereblon. (15-2-1) A heterocyclic compound or a salt thereof, wherein EUB is a combination of the embodiments described in the following (15-5) and (15-8). (15-3) The heterocyclic compound or a salt thereof according to (1-2), wherein EUB is a group capable of binding to VHL. (15-4) The heterocyclic compound or salt thereof according to (1-2), wherein EUB is a group capable of binding to cereblon. (15-5) EUB is a group capable of binding to cereblon, and the group capable of binding to cereblon is represented by the following formula (E-1): G is CR G or N, R G But H or C 1-６ is alkyl, Z is the following formula (Z-1), (Z-2), (Z-3), (Z-4), (Z-5), (Z-6), (Z-7), (Z-8), (Z-9), (Z-10), (Z-11), (Z-12), (Z-13), (Z-14), (Z-15), 1 group selected from the group consisting of (Z-16), (Z-17), (Z-18), (Z-19), (Z-20), (Z-21), (Z-22), (Z-23), (Z-24), (Z-25), (Z-26) and (Z-27), Here, the formulas (Z-1), (Z-2), (Z-3), (Z-4), (Z-5), (Z-6), (Z-7), (Z-8), (Z-9), (Z-10), (Z-11), (Z-12), (Z-13), (Z-14), (Z-15), (Z-16), (Z -17), (Z-18), (Z-19), (Z-20), (Z-21), (Z-22), (Z-23), (Z-24), (Z-25), (Z-26) and (Z-27), ring B1 and ring B2 are L P It forms a bond with provided that when G is N, Z is a group selected from the group consisting of formulas (Z-1), (Z-16), (Z-17), (Z-18), (Z-19), (Z-20), (Z-21), (Z-22), (Z-23), (Z-24), (Z-25), (Z-26) and (Z-27), R Z1 are, independently of each other, optionally substituted C 1-6 Alkyl, halogen, cyano, -OH, -O-(optionally substituted C 1-6 alkyl), -S-(optionally substituted C 1-6alkyl), -NH-(optionally substituted C 1-6 alkyl) or -N-(optionally substituted C 1-6 alkyl)2, p is an integer from 0 to 2, R Z2 , R Z3 , R Z4 and R Z5 are each independently H or optionally substituted C 1-6 is alkyl, M is a bond, -O-, -S-, -N(R M )- or optionally substituted C 1-３ is alkylene, R M is H or optionally substituted C 1-３ is alkyl, Ring B1 is a benzene ring or a 6-membered heterocycle, where R Z1 and L P forms a bond with the carbon atom constituting ring B1, Ring B2 is a benzene ring or a 5- or 6-membered heterocycle, Here, M, R Z1 and L P The heterocyclic compound or salt thereof according to (1-2), wherein R 1 is a carbon atom constituting ring B2 and R 2 is a carbon atom constituting ring B3. (15-6) EUB is a group capable of binding to cereblon, and the group capable of binding to cereblon is represented by the following formula (E-1): G is CH or N; Z is a group selected from the group consisting of the following formulae (Z-1A), (Z-1B), (Z-5A), (Z-5B), (Z-14A), (Z-14B), (Z-14C), (Z-15A), (Z-16A), (Z-16B), (Z-16C), (Z-16D), (Z-20A), (Z-22A), (Z-23A), (Z-23B), (Z-23C), (Z-23D), (Z-23E), (Z-23F) and (Z-24A), Here, the benzene ring or 6-membered heterocycle in the formulae (Z-1A), (Z-1B), (Z-5A), (Z-5B), (Z-14A), (Z-14B), (Z-14C), (Z-15A), (Z-16A), (Z-16B), (Z-16C), (Z-16D), (Z-20A), (Z-22A), (Z-23A), (Z-23B), (Z-23C), (Z-23D), (Z-23E) and (Z-23F) is L P The benzene ring in (Z-24A) is L P It forms a bond with The heterocyclic compound or salt thereof according to (1-2), wherein when G is N, Z is a group selected from the group consisting of (Z-1A), (Z-16A), (Z-16B), (Z-16C), (Z-16D), (Z-20A), (Z-22A), (Z-23A), (Z-23B), (Z-23C), (Z-23D), (Z-23E), (Z-23F), and (Z-24A). (15-7) EUB is a group capable of binding to cereblon, and the group capable of binding to cereblon is represented by the following formula (E-1): G is CH or N; Z is a group selected from the group consisting of the following formula (Z-1A) or (Z-16A): Here, the benzene ring in the formulas (Z-1A) and (Z-16A) is L P The heterocyclic compound or salt thereof according to (1-2), wherein (15-8) EUB is a group capable of binding to VHL, and the group capable of binding to VHL is represented by the following formula (E-2): R 5 may be substituted C 1-6 Alkyl, optionally substituted C 3-6 cycloalkyl or an optionally substituted 4- to 6-membered heterocycloalkyl containing one heteroatom selected from the group consisting of oxygen, sulfur, and nitrogen; R 6a , R 6b are each independently H or optionally substituted C 1-6alkyl, or R 6a , R 6b may be substituted together with the carbon to which they are attached. 3-6 cycloalkyl or an optionally substituted 4- to 6-membered heterocycloalkyl containing one heteroatom selected from the group consisting of oxygen, sulfur, and nitrogen; R 7 But H, halogen, C 1-3 Alkyl, -SO2CH3, C 3-6 an optionally substituted 4- to 6-membered heterocycloalkyl containing 1 to 2 heteroatoms selected from the group consisting of cycloalkyl, oxygen, sulfur, and nitrogen; an optionally substituted 5-membered heteroaryl containing 1 to 4 heteroatoms selected from the group consisting of oxygen, sulfur, and nitrogen; or a 6-membered heteroaryl containing 1 to 3 nitrogen atoms; R P1 is OH or F, R P2a is H or F, R P2b is H, The heterocyclic compound or a salt thereof according to (1-2), wherein the ring group C is an optionally substituted phenylene or an optionally substituted 6-membered heteroarylene containing 1 to 3 nitrogen atoms. (15-9) EUB is a group capable of binding to VHL, and the group capable of binding to VHL is represented by the following formula (E-2): R 5 is isopropyl, R 6a is H and R 6b is hydroxymethyl or —CH—OP(═O)(OH), R 7 is a group selected from the group consisting of the following formulas (XVII-2), (XVIII-2), (XIX-2), (XIX-3), (XX), and (XXII-2), R P1 is OH, R P2a is H, RP2b is H, The ring group C is represented by the following formula (XXVII): *R7 is R 7 (showing the bond with W 1 , W 2 and (1-2) are both CH. (15-10) R P1 is OH, R P2a is H, R P2b is H. The heterocyclic compound or a salt thereof according to (15-8). (16-1) R 5 may be substituted C 1-6 Alkyl, optionally substituted C 3-6 The heterocyclic compound or a salt thereof according to (15-8), which is a cycloalkyl or an optionally substituted 4- to 6-membered heterocycloalkyl containing one heteroatom selected from the group consisting of oxygen, sulfur, and nitrogen. (16-2) R 5 is methyl, ethyl, isopropyl, tert-butyl, or C 3-6 The heterocyclic compound or a salt thereof according to (15-8), which is cycloalkyl. (16-3) R 5 is ethyl, isopropyl, tert-butyl or C 3-6 The heterocyclic compound or a salt thereof according to (15-8), which is cycloalkyl. (16-4) R 5 isopropyl or C 3-6 The heterocyclic compound or a salt thereof according to (15-8), which is cycloalkyl. (16-5) R 5 The heterocyclic compound or a salt thereof according to (15-8), wherein is isopropyl. (17-1) R 6a , R 6b are each independently H or optionally substituted C 1-6 alkyl, or R 6a , R 6bmay be substituted together with the carbon to which they are attached. 3-6 The heterocyclic compound or a salt thereof according to (15-8), which may form a cycloalkyl or an optionally substituted 4- to 6-membered heterocycloalkyl containing one heteroatom selected from the group consisting of oxygen, sulfur, and nitrogen. (17-2) R 6a , R 6b are independently H or C 1-3 alkyl, 1-3 The alkyl may be substituted with a group selected from the group consisting of F, OH, OCH3, and N(CH3)2, or R 6a , R 6b However, together with the carbon to which they are bonded, C 3-6 The heterocyclic compound or a salt thereof according to (15-8), which may form a cycloalkyl. (17-3) R 6a , R 6b are independently H or C 1-3 alkyl, 1-3 The alkyl may be substituted with a group selected from the group consisting of F, OH, and N(CH3)2, or R 6a , R 6b may be taken together with the carbon to which they are attached to form cyclopropyl. (17-4) R 6a is H and R 6b C optionally substituted with OH 1-3 The heterocyclic compound or a salt thereof according to (15-8), wherein the heterocyclic compound is alkyl. (17-5) R 6a is H and R 6b is hydroxymethyl. (17-6) R 6a is H and R 6b C optionally substituted with OH or OP(=O)(OH) 1-3 The heterocyclic compound or a salt thereof according to (15-8), wherein the heterocyclic compound is alkyl. (17-7) R 6ais H and R 6b is hydroxymethyl or —CH2—OP(═O)(OH)2, or a salt thereof according to (15-8). (17-8) R 6a is H and R 6b is —CH2—OP(═O)(OH)2, or a salt thereof according to (15-8). (18-1) R 7 But H, halogen, C 1-3 Alkyl, -SO2CH3, C 3-6 The heterocyclic compound or a salt thereof according to (15-8), which is an optionally substituted 4- to 6-membered heterocycloalkyl containing 1 to 2 heteroatoms selected from the group consisting of cycloalkyl, oxygen, sulfur, and nitrogen, an optionally substituted 5-membered heteroaryl containing 1 to 4 heteroatoms selected from the group consisting of oxygen, sulfur, and nitrogen, or a 6-membered heteroaryl containing 1 to 3 nitrogen atoms. (18-2) R 7 But H, halogen, C 1-3 Alkyl, -SO2CH3, C 3-6 cycloalkyl, or a group selected from the group consisting of the following formulas (XVII), (XVIII), (XIX), (XX), (XXI), (XXII), (XXIII), (XXIV), (XXV), and (XXVI), R 7a , R 7b may be substituted with H or OH independently of each other. 1-3 The heterocyclic compound or a salt thereof according to (15-8), wherein the heterocyclic compound is alkyl. (18-3) R 7 is a halogen or a group selected from the group consisting of the following formulas (XVII), (XVIII), (XIX), (XX), (XXI) and (XXII), R 7a , R 7b may be substituted with H or OH independently of each other. 1-3 The heterocyclic compound or a salt thereof according to (15-8), wherein the heterocyclic compound is alkyl. (18-4) R7 is represented by the following formula (XVII), formula (XVIII), formula (XIX) or formula (XX), R 7a C optionally substituted with OH 1-3 The heterocyclic compound or a salt thereof according to (15-8), wherein the heterocyclic compound is alkyl. (18-5) R 7 is represented by the following formula (XVII) or formula (XIX), R 7a But C 1-3 The heterocyclic compound or a salt thereof according to (15-8), wherein the heterocyclic compound is alkyl. (18-6) R 7 is the following formula (XVII), R 7a But C 1-3 The heterocyclic compound or a salt thereof according to (15-8), wherein the heterocyclic compound is alkyl. (18-7) R 7 The heterocyclic compound or a salt thereof according to (15-8), wherein (18-8) R 7 is a group selected from the group consisting of the following formulas (XVII-2), (XVIII-2), (XIX-2), (XIX-3), (XX), and (XXII-2): (19-1) The heterocyclic compound or a salt thereof according to (15-8), wherein the ring group C is an optionally substituted phenylene or an optionally substituted 6-membered heteroarylene containing 1 to 3 nitrogen atoms. (19-2) The ring group C is represented by the following formula (XXVII): *R7 is R 7 (showing the bond with W 1 and W 2 but, (i)W 1 is CH and W 2 is C-SO2CH3, or (ii) W 1 , W 2are, independently of one another, CH, CF, CCl, CCH3 or N, However, in the case of (i) above, R 7 is H. The heterocyclic compound or a salt thereof according to (15-8). (19-3) The ring group C is represented by the following formula (XXVII): *R7 is R 7 (showing the bond with W 1 , W 2 are each independently CH or N, or a salt thereof according to (15-8). (19-4) The ring group C is represented by the following formula (XXVII): *R7 is R 7 (showing the bond with W 1 , W 2 are each independently CH, CF, CCl, CCH3, or N, or a salt thereof according to (15-8). (19-5) The ring group C is represented by the following formula (XXVII): *R7 is R 7 (showing the bond with W 1 , W 2 and (15-8) are both CH. (20) A heterocyclic compound or a salt thereof which is a combination of two or more of the embodiments described in (1-1) to (19-5) above that do not contradict each other. Certain embodiments of specific heterocyclic compounds used as the drug constituting the antibody-drug conjugate or salt thereof of the present invention include the following compounds or salts thereof: (4R)-1-[(2S)-2-(4-{4-[({6-cyclopropyl-4-[(1S,4S)-2,5-diazabicyclo[2.2.1]heptan-2-yl]-7-(6-fluoro-5-methyl-1H-indazol-4-yl)-2-[(oxan-4-yl)oxy]quinazolin-8-yl}oxy)methyl]phenyl}-1H-1,2,3-triazol-1-yl)-3-methylbutanoyl]-4-hydroxy-N-{(1R)-2-hydroxy-1-[4-(4-methyl-1,3-thiazol-5-yl)phenyl]ethyl}-L-prolinamide, (4R)-1-[(2S)-2-(4-{4-[({6-cyclopropyl-4-[(1S,4S)-2,5-diazabicyclo[2.2.1]heptan-2-yl]-7-(6-fluoro-5-methyl-1H-indazol-4-yl)-2-[(oxan-4-yl)oxy]quinazolin-8-yl}oxy)methyl]phenyl}-1H-1,2,3-triazol-1-yl)-3-methylbutanoyl]-4-hydroxy-N-{(1R)-2-hydroxy-1-[4-(2-oxo-1,3-oxazolidin-3-yl)phenyl]ethyl}-L-prolinamide, (4R)-1-[(2S)-2-(4-{4-[({6-cyclopropyl-4-[(1S,4S)-2,5-diazabicyclo[2.2.1]heptan-2-yl]-7-(6-fluoro-5-methyl-1H-indazol-4-yl)-2-[(oxan-4-yl)oxy]quinazolin-8-yl}oxy)methyl]phenyl}-1H-1,2,3-triazol-1-yl)-3-methylbutanoyl]-4-hydroxy-N-{(1R)-2-hydroxy-1-[4-(1-methyl-1H-pyrazol-5-yl)phenyl]ethyl}-L-prolinamide, (4R)-1-[(2S)-2-(4-{4-[({6-cyclopropyl-4-[(1S,4S)-2,5-diazabicyclo[2.2.1]heptan-2-yl]-7-(6-fluoro-5-methyl-1H-indazol-4-yl)-2-[(2S)-2-methoxypropoxy]quinazolin-8-yl}oxy)methyl]phenyl}-1H-1,2,3-triazol-1-yl)-3-methylbutanoyl]-4-hydroxy-N-{(1R)-2-hydroxy-1-[4-(4-methyl-1,3-thiazol-5-yl)phenyl]ethyl}-L-prolinamide, (4R)-1-[(2S)-2-(4-{4-[({6-cyclopropyl-4-[(1S,4S)-2,5-diazabicyclo[2.2.1]heptan-2-yl]-7-(6-fluoro-5-methyl-1H-indazol-4-yl)-2-[(2S)-2-methoxypropoxy]quinazolin-8-yl}oxy)methyl]phenyl}-1H-1,2,3-triazol-1-yl)-3-methylbutanoyl]-N-{(1R)-1-[4-(1-ethyl-1H-pyrazol-5-yl)phenyl]-2-hydroxyethyl}-4-hydroxy-L-prolinamide, (4R)-1-[(2S)-2-(4-{4-[({6-cyclopropyl-4-[(1S,4S)-2,5-diazabicyclo[2.2.1]heptan-2-yl]-7-(6-fluoro-5-methyl-1H-indazol-4-yl)-2-[(2S)-2-methoxypropoxy]quinazolin-8-yl}oxy)methyl]phenyl}-1H-1,2,3-triazol-1-yl)-3-methylbutanoyl]-4-hydroxy-N-{(1R)-2-hydroxy-1-[4-(4-methyl-1,3-oxazol-5-yl)phenyl]ethyl}-L-prolinamide, (4R)-1-[(2S)-2-{4-[4-({[(7M)-6-cyclopropyl-7-(6-fluoro-5-methyl-1H-indazol-4-yl)-2-[(2S)-2-methoxypropoxy]-4-{methyl[(3S)-pyrrolidin-3-yl]amino}quinazolin-8-yl]oxy}methyl)phenyl]-1H-1,2,3-triazol-1-yl}-3-methylbutanoyl]-4-hydroxy-N-{(1R)-2-hydroxy-1-[4-(4-methyl-1,3-thiazol-5-yl)phenyl]ethyl}-L-prolinamide, (4R)-1-[(2S)-2-{4-[4-({[(7M)-6-cyclopropyl-7-(6-fluoro-5-methyl-1H-indazol-4-yl)-2-[(2S)-2-methoxypropoxy]-4-{methyl[(3S)-pyrrolidin-3-yl]amino}quinazolin-8-yl]oxy}methyl)phenyl]-1H-1,2,3-triazol-1-yl}-3-methylbutanoyl]-N-{(1R)-1-[4-(1-ethyl-1H-pyrazol-5-yl)phenyl]-2-hydroxyethyl}-4-hydroxy-L-prolinamide, 3-(5-{[(3S)-4-{4-[({(7M)-6-cyclopropyl-4-[(1S,4S)-2,5-diazabicyclo[2.2.1]heptan-2-yl]-7-(6-fluoro-5-methyl-1H-indazol-4-yl)-2-[(oxan-4-yl)oxy]quinazolin-8-yl}oxy)methyl]benzoyl}-3-methylpiperazin-1-yl]methyl}-3-methyl-2-oxo-2,3-dihydro-1H-benzimidazol-1-yl)piperidine-2,6-dione, 1-(6-{[(3S)-4-{4-[({(7M)-6-cyclopropyl-4-[(1S,4S)-2,5-diazabicyclo[2.2.1]heptan-2-yl]-7-(6-fluoro-5-methyl-1H-indazol-4-yl)-2-[(oxan-4-yl)oxy]quinazolin-8-yl}oxy)methyl]benzoyl}-3-methylpiperazin-1-yl]methyl}-1-methyl-1H-indazol-3-yl)-1,3-diazinan-2,4-dione, 3-(5-{[(3S)-4-{4-[({(7M)-6-cyclopropyl-4-[(1S,4S)-2,5-diazabicyclo[2.2.1]heptan-2-yl]-7-(6-fluoro-5-methyl-1H-indazol-4-yl)-2-[(2S)-2-methoxypropoxy]quinazolin-8-yl}oxy)methyl]benzoyl}-3-methylpiperazin-1-yl]methyl}-3-methyl-2-oxo-2,3-dihydro-1H-benzimidazol-1-yl)piperidine-2,6-dione, or Phosphate = dihydrogen = (2R)-2-({(4R)-1-[(2S)-2-{4-[4-({[(7M)-6-cyclopropyl-7-(6-fluoro-5-methyl-1H-indazol-4-yl)-2-[(2S)-2-methoxypropoxy]-4-{methyl[(3S)-pyrrolidin-3-yl]amino}quinazolin-8-yl]oxy}methyl)phenyl]-1H-1,2,3-triazol-1-yl}-3-methylbutanoyl]-4-hydroxy-L-prolyl}amino)-2-[4-(1H-1,2,4-triazol-1-yl)phenyl]ethyl. Certain embodiments of specific heterocyclic compounds used as the drug constituting the antibody-drug conjugate or salt thereof of the present invention include the following compounds or salts thereof: (4R)-1-[(2S)-2-(4-{4-[({6-cyclopropyl-4-[(1S,4S)-2,5-diazabicyclo[2.2.1]heptan-2-yl]-7-(6-fluoro-5-methyl-1H-indazol-4-yl)-2-[(oxan-4-yl)oxy]quinazolin-8-yl}oxy)methyl]phenyl}-1H-1,2,3-triazol-1-yl)-3-methylbutanoyl]-4-hydroxy-N-{(1R)-2-hydroxy-1-[4-(4-methyl-1,3-thiazol-5-yl)phenyl]ethyl}-L-prolinamide, (4R)-1-[(2S)-2-(4-{4-[({6-cyclopropyl-4-[(1S,4S)-2,5-diazabicyclo[2.2.1]heptan-2-yl]-7-(6-fluoro-5-methyl-1H-indazol-4-yl)-2-[(oxan-4-yl)oxy]quinazolin-8-yl}oxy)methyl]phenyl}-1H-1,2,3-triazol-1-yl)-3-methylbutanoyl]-4-hydroxy-N-{(1R)-2-hydroxy-1-[4-(2-oxo-1,3-oxazolidin-3-yl)phenyl]ethyl}-L-prolinamide, (4R)-1-[(2S)-2-(4-{4-[({6-cyclopropyl-4-[(1S,4S)-2,5-diazabicyclo[2.2.1]heptan-2-yl]-7-(6-fluoro-5-methyl-1H-indazol-4-yl)-2-[(oxan-4-yl)oxy]quinazolin-8-yl}oxy)methyl]phenyl}-1H-1,2,3-triazol-1-yl)-3-methylbutanoyl]-4-hydroxy-N-{(1R)-2-hydroxy-1-[4-(1-methyl-1H-pyrazol-5-yl)phenyl]ethyl}-L-prolinamide, (4R)-1-[(2S)-2-(4-{4-[({6-cyclopropyl-4-[(1S,4S)-2,5-diazabicyclo[2.2.1]heptan-2-yl]-7-(6-fluoro-5-methyl-1H-indazol-4-yl)-2-[(2S)-2-methoxypropoxy]quinazolin-8-yl}oxy)methyl]phenyl}-1H-1,2,3-triazol-1-yl)-3-methylbutanoyl]-4-hydroxy-N-{(1R)-2-hydroxy-1-[4-(4-methyl-1,3-thiazol-5-yl)phenyl]ethyl}-L-prolinamide, (4R)-1-[(2S)-2-(4-{4-[({6-cyclopropyl-4-[(1S,4S)-2,5-diazabicyclo[2.2.1]heptan-2-yl]-7-(6-fluoro-5-methyl-1H-indazol-4-yl)-2-[(2S)-2-methoxypropoxy]quinazolin-8-yl}oxy)methyl]phenyl}-1H-1,2,3-triazol-1-yl)-3-methylbutanoyl]-N-{(1R)-1-[4-(1-ethyl-1H-pyrazol-5-yl)phenyl]-2-hydroxyethyl}-4-hydroxy-L-prolinamide, (4R)-1-[(2S)-2-(4-{4-[({6-cyclopropyl-4-[(1S,4S)-2,5-diazabicyclo[2.2.1]heptan-2-yl]-7-(6-fluoro-5-methyl-1H-indazol-4-yl)-2-[(2S)-2-methoxypropoxy]quinazolin-8-yl}oxy)methyl]phenyl}-1H-1,2,3-triazol-1-yl)-3-methylbutanoyl]-4-hydroxy-N-{(1R)-2-hydroxy-1-[4-(4-methyl-1,3-oxazol-5-yl)phenyl]ethyl}-L-prolinamide, (4R)-1-[(2S)-2-{4-[4-({[(7M)-6-cyclopropyl-7-(6-fluoro-5-methyl-1H-indazol-4-yl)-2-[(2S)-2-methoxypropoxy]-4-{methyl[(3S)-pyrrolidin-3-yl]amino}quinazolin-8-yl]oxy}methyl)phenyl]-1H-1,2,3-triazol-1-yl}-3-methylbutanoyl]-4-hydroxy-N-{(1R)-2-hydroxy-1-[4-(4-methyl-1,3-thiazol-5-yl)phenyl]ethyl}-L-prolinamide, (4R)-1-[(2S)-2-{4-[4-({[(7M)-6-cyclopropyl-7-(6-fluoro-5-methyl-1H-indazol-4-yl)-2-[(2S)-2-methoxypropoxy]-4-{methyl[(3S)-pyrrolidin-3-yl]amino}quinazolin-8-yl]oxy}methyl)phenyl]-1H-1,2,3-triazol-1-yl}-3-methylbutanoyl]-N-{(1R)-1-[4-(1-ethyl-1H-pyrazol-5-yl)phenyl]-2-hydroxyethyl}-4-hydroxy-L-prolinamide, 3-(5-{[(3S)-4-{4-[({(7M)-6-cyclopropyl-4-[(1S,4S)-2,5-diazabicyclo[2.2.1]heptan-2-yl]-7-(6-fluoro-5-methyl-1H-indazol-4-yl)-2-[(oxan-4-yl)oxy]quinazolin-8-yl}oxy)methyl]benzoyl}-3-methylpiperazin-1-yl]methyl}-3-methyl-2-oxo-2,3-dihydro-1H-benzimidazol-1-yl)piperidine-2,6-dione, 1-(6-{[(3S)-4-{4-[({(7M)-6-cyclopropyl-4-[(1S,4S)-2,5-diazabicyclo[2.2.1]heptan-2-yl]-7-(6-fluoro-5-methyl-1H-indazol-4-yl)-2-[(oxan-4-yl)oxy]quinazolin-8-yl}oxy)methyl]benzoyl}-3-methylpiperazin-1-yl]methyl}-1-methyl-1H-indazol-3-yl)-1,3-diazinan-2,4-dione, or 3-(5-{[(3S)-4-{4-[({(7M)-6-cyclopropyl-4-[(1S,4S)-2,5-diazabicyclo[2.2.1]heptan-2-yl]-7-(6-fluoro-5-methyl-1H-indazol-4-yl)-2-[(2S)-2-methoxypropoxy]quinazolin-8-yl}oxy)methyl]benzoyl}-3-methylpiperazin-1-yl]methyl}-3-methyl-2-oxo-2,3-dihydro-1H-benzimidazol-1-yl)piperidine-2,6-dione. Certain embodiments of specific heterocyclic compounds used as the drug constituting the antibody-drug conjugate or salt thereof of the present invention include the following compounds or salts thereof: (4R)-1-[(2S)-2-(4-{4-[({(7M)-6-cyclopropyl-4-[(1S,4S)-2,5-diazabicyclo[2.2.1]heptan-2-yl]-7-(6-fluoro-5-methyl-1H-indazol-4-yl)-2-[(oxan-4-yl)oxy]quinazolin-8-yl}oxy)methyl]phenyl}-1H-1,2,3-triazol-1-yl)-3-methylbutanoyl]-4-hydroxy-N-{(1R)-2-hydroxy-1-[4-(4-methyl-1,3-thiazol-5-yl)phenyl]ethyl}-L-prolinamide, (4R)-1-[(2S)-2-(4-{4-[({(7M)-6-cyclopropyl-4-[(1S,4S)-2,5-diazabicyclo[2.2.1]heptan-2-yl]-7-(6-fluoro-5-methyl-1H-indazol-4-yl)-2-[(oxan-4-yl)oxy]quinazolin-8-yl}oxy)methyl]phenyl}-1H-1,2,3-triazol-1-yl)-3-methylbutanoyl]-4-hydroxy-N-{(1R)-2-hydroxy-1-[4-(2-oxo-1,3-oxazolidin-3-yl)phenyl]ethyl}-L-prolinamide, (4R)-1-[(2S)-2-(4-{4-[({(7M)-6-cyclopropyl-4-[(1S,4S)-2,5-diazabicyclo[2.2.1]heptan-2-yl]-7-(6-fluoro-5-methyl-1H-indazol-4-yl)-2-[(oxan-4-yl)oxy]quinazolin-8-yl}oxy)methyl]phenyl}-1H-1,2,3-triazol-1-yl)-3-methylbutanoyl]-4-hydroxy-N-{(1R)-2-hydroxy-1-[4-(1-methyl-1H-pyrazol-5-yl)phenyl]ethyl}-L-prolinamide, (4R)-1-[(2S)-2-(4-{4-[({(7M)-6-cyclopropyl-4-[(1S,4S)-2,5-diazabicyclo[2.2.1]heptan-2-yl]-7-(6-fluoro-5-methyl-1H-indazol-4-yl)-2-[(2S)-2-methoxypropoxy]quinazolin-8-yl}oxy)methyl]phenyl}-1H-1,2,3-triazol-1-yl)-3-methylbutanoyl]-4-hydroxy-N-{(1R)-2-hydroxy-1-[4-(4-methyl-1,3-thiazol-5-yl)phenyl]ethyl}-L-prolinamide, (4R)-1-[(2S)-2-(4-{4-[({(7M)-6-cyclopropyl-4-[(1S,4S)-2,5-diazabicyclo[2.2.1]heptan-2-yl]-7-(6-fluoro-5-methyl-1H-indazol-4-yl)-2-[(2S)-2-methoxypropoxy]quinazolin-8-yl}oxy)methyl]phenyl}-1H-1,2,3-triazol-1-yl)-3-methylbutanoyl]-N-{(1R)-1-[4-(1-ethyl-1H-pyrazol-5-yl)phenyl]-2-hydroxyethyl}-4-hydroxy-L-prolinamide, or (4R)-1-[(2S)-2-(4-{4-[({(7M)-6-cyclopropyl-4-[(1S,4S)-2,5-diazabicyclo[2.2.1]heptan-2-yl]-7-(6-fluoro-5-methyl-1H-indazol-4-yl)-2-[(2S)-2-methoxypropoxy]quinazolin-8-yl}oxy)methyl]phenyl}-1H-1,2,3-triazol-1-yl)-3-methylbutanoyl]-4-hydroxy-N-{(1R)-2-hydroxy-1-[4-(4-methyl-1,3-oxazol-5-yl)phenyl]ethyl}-L-prolinamide. Certain embodiments of specific heterocyclic compounds used as the drug constituting the antibody-drug conjugate or salt thereof of the present invention include the following compounds or salts thereof: Phosphate = dihydrogen = (2R)-2-({(4R)-1-[(2S)-2-{4-[4-({[(7M)-6-cyclopropyl-7-(6-fluoro-5-methyl-1H-indazol-4-yl)-2-[(2S)-2-methoxypropoxy]-4-{methyl[(3S)-pyrrolidin-3-yl]amino}quinazolin-8-yl]oxy}methyl)phenyl]-1H-1,2,3-triazol-1-yl}-3-methylbutanoyl]-4-hydroxy-L-prolyl}amino)-2-[4-(1H-1,2,4-triazol-1-yl)phenyl]ethyl. Further, other examples of heterocyclic compounds having the activity of inducing degradation of G12D mutant KRAS protein, which can be used as drugs constituting the antibody-drug conjugate or salt thereof of the present invention, are shown below. Heterocyclic compounds of the following formula (TP-1) or (TP-2) (see WO 2022 / 148421). Heterocyclic compounds of the following formula (TP-3), (TP-4), (TP-5), (TP-6) or (TP-7) (see WO 2022 / 148422). Heterocyclic compounds represented by the general formula WLT (Wherein W is a G12D mutant KRAS protein binding ligand represented by the following formula (TP-8) or (TP-9), X is N, CH, CF, C—Cl, C—CH3, C—C2H5 or C—C3H7; R 1 is a substituted or unsubstituted hydroxyl group, amino group, or mercapto group, R 2 and R 3 are each independently H, halogen, or halomethyl (monohalomethyl, dihalomethyl, or trihalomethyl), or R 2 and R 3together with the benzene ring to which they are attached form a substituted or unsubstituted fused benzene ring (including, but not limited to, a naphthalene ring), which fused benzene ring may contain one or more, for example, two or three, halogens, hydroxyl groups, amino groups, halomethyl groups, C 1-2 Alkyl and C 2-4 alkynyl, T is a group capable of binding to an E3 ubiquitin ligase, L is a bivalent linking moiety for connecting W and T. See Chinese Patent Application Publication No. 115785199. Heterocyclic compounds of the following formula (TP-10), (TP-11), (TP-12), (TP-13), (TP-14), (TP-15), (TP-16) or (TP-17) (see Chinese Patent Application Publication No. 115785199). Heterocyclic compounds of the following formula (TP-18) (In the formula, Ar is an optionally substituted aryl or an optionally substituted heteroaryl, X is H or a halogen, L is a linking moiety, and E is a group capable of binding to an E3 ubiquitin ligase. See WO 2023 / 077441.) Heterocyclic compounds of the following formula (TP-19), (TP-20), (TP-21) or (TP-22) (see WO 2023 / 077441). Heterocyclic compounds of the following formula (TP-23) (In the formula, R2a is a halogen and R 3a is a 7-8 membered bridged heterocycloalkyl containing two N's, and R 5a is H and R 6 and R 7 are independently H, halogen, or C 1-12 Alkyl or C 2-6 alkynyl, and X a teeth and M 1 is a 3- to 9-membered heterocycloalkyl; Y 1 does not exist, and L a teeth wherein n1 is 1, 2, or 3, n4 is 0, 1, or 2, n5 is an integer from 1 to 5, and n6 is 0, 1, or 2; and Q a is a group capable of binding to an E3 ubiquitin ligase. See WO 2022 / 228576. Heterocyclic compounds of the following formula (TP-24), (TP-25), (TP-26) or (TP-27) (see WO 2022 / 228576). Heterocyclic compounds of the following formula (TP-28) or (TP-29) (In the formula, R 1 is H or halogen, n is 0, 1, 2, 3 or 4, and R 2 is 8-chloronaphthalen-1-yl, 3-hydroxynaphthalen-1-yl, 8-ethynyl-7-fluoro-3-hydroxynaphthalen-1-yl, or 8-ethynyl-7-fluoronaphthalen-1-yl, and L is and M is See WO 2023 / 280026. A heterocyclic compound represented by the following formula (TP-30) or (TP-31) (see WO 2023 / 280026). 2. Linker (L A ) As used herein, the linker (L) constituting the antibody-drug conjugate or salt thereof of the present invention A ) is a bifunctional moiety that attaches one or more drugs (D) to an antibody or antigen-binding fragment (Ab) to form an antibody-drug conjugate. A In one embodiment of the linker (L), the linker has a partial structure that can be cleaved in vivo, and is not particularly limited to a linker having a partial structure that can be cleaved by an enzyme such as cathepsin B. When the linker is cleaved, the drug (D) is released in vivo. A In one embodiment, D is bonded to D at the nitrogen atom of any -NH- or oxygen atom of any -OH contained in D, and in another embodiment, V 2 or nitrogen atoms contained in W *LA It binds to D at the bond shown. The linker (L A An embodiment of the linker is a linker represented by the following formula (XXVIII): (In the formula, Str is a stretcher unit, which binds to Ab and CLL, and r is 0 or 1; CLL is a partial structure that can be cleaved in vivo. Sp is a spacer unit and binds to CLL and D; t is 0 or 1; *Ab indicates the binding site with Ab. As used herein, a "stretcher unit (Str)" is a structural unit that, when present, connects Ab and CLL. The stretcher unit forms a covalent bond with a functional group contained in Ab. Functional groups contained in Ab that form a covalent bond with the stretcher unit include, but are not limited to, mercapto groups, amino groups, hydroxyl groups, and carboxyl groups, and in one embodiment, mercapto groups. Mercapto groups that can be used to form covalent bonds with Ab can also be generated by reducing intramolecular disulfide bonds contained in Ab. Note that when r is 0, no stretcher unit is present, and the in vivo cleavable partial structure (CLL) directly binds to Ab. One embodiment of a stretcher unit (Str) is shown below. (21-1) Stretcher unit of formula (ST-1) (In the formula, R st1 may be substituted C 1-12 Alkylene, -(CH2CH2O) a1 -C 1-6 Alkylene-, -C 1-6 Alkylene-(OCH2CH2) a2 -, -Optionally substituted C 1-6 Alkylene-NH-C(=O)-optionally substituted C 1-6 Alkylene-, -optionally substituted C 1-6 Alkylene-C(=O)-NH-optionally substituted C 1-6 Alkylene-, optionally substituted C 1-6 Alkylene-C(=O)-NH-(CH2CH2O) a3 -C 1-6 Alkylene- or optionally substituted C 1-6 Alkylene-NH-C(=O)-(CH2CH2O) a4 -C 1-6 alkylene-, a1, a2, a3, and a4 are each an integer from 1 to 10, *Ab indicates the binding site with Ab). (21-2) R st1 But C 1-12The stretcher unit according to (21-1), which is alkylene. (21-3) R st1 But C 3-8 The stretcher unit according to (21-1), which is alkylene. (21-4) R st1 is a C5 alkylene. (21-5) Stretcher unit of formula (ST-2) or (ST-3) (In the formula, R st1 may be substituted C 1-12 Alkylene, -(CH2CH2O) a1 -C 1-6 Alkylene-, -C 1-6 Alkylene-(OCH2CH2) a2 -, -Optionally substituted C 1-6 Alkylene-NH-C(=O)-optionally substituted C 1-6 Alkylene-, -optionally substituted C 1-6 Alkylene-C(=O)-NH-optionally substituted C 1-6 Alkylene-, optionally substituted C 1-6 Alkylene-C(=O)-NH-(CH2CH2O) a3 -C 1-6 Alkylene- or optionally substituted C 1-6 Alkylene-NH-C(=O)-(CH2CH2O) a4 -C 1-6 alkylene-, a1, a2, a3, and a4 are each an integer from 1 to 10, *Ab indicates the binding site with Ab). (21-6) R st1 But C 1-12 The stretcher unit according to (21-5), which is alkylene. (21-7) R st1 But C 3-8 The stretcher unit according to (21-5), which is alkylene. (21-8) R st1 is a C5 alkylene. In the present invention, embodiments of the "in vivo cleavable partial structure (CLL)" are shown below. (22-1) Partial structure of formula (CL-1) that can be cleaved in vivo (In the formula, R AA are each independently H, methyl, isopropyl, isobutyl, sec-butyl, benzyl, p-hydroxybenzyl, hydroxymethyl, 1-hydroxyethyl, -CH2-C(=O)-OH, -(CH2)2-C(=O)-OH, -CH2-C(=O)-NH2, -(CH2)2-C(=O)-NH2, -(CH2)4-NH2, -(CH2)3-NH-C(=NH)-NH2, -(CH2)3-NH-C(=O)-NH2, -CH2-SH, or -CH2-S-CH3, or a group selected from the group consisting of the following formulae (RAA-1) and (RAA-2), d is an integer from 1 to 6, *STR indicates the binding site with Str). (22-2) R AA are each independently H, methyl, isopropyl, benzyl, -(CH2)4-NH2, -(CH2)3-NH-C(=NH)-NH2, or -(CH2)3-NH-C(=O)-NH2, and d is an integer of 2 to 4. (22-3) R AA are each independently methyl, isopropyl, benzyl, -(CH2)4-NH2, -(CH2)3-NH-C(=NH)-NH2, or -(CH2)3-NH-C(=O)-NH2, and d is 2. (22-4) R AA are each independently methyl, isopropyl, or —(CH2)3—NH—C(═O)—NH2, and d is 2. (22-5) R AA are each independently methyl or isopropyl, and d is 2. (22-6) RAA are each independently isopropyl or -(CH2)3-NH-C(=O)-NH2, and d is 2. (22-7) R AA are each independently H or benzyl, and d is 4. As used herein, the term "spacer unit (Sp)" refers to a structural unit that, when present, connects CLL to drug (D). When present, the spacer unit, in some embodiments, forms a covalent bond with any group of drug (D), in some embodiments, forms a covalent bond with any nitrogen atom of -NH- or oxygen atom of -OH of drug (D), in some embodiments, forms a covalent bond with the nitrogen atom of one secondary amino group of drug (D) represented by formula (VI), formula (VII), formula (VIII), formula (IX), formula (X), formula (XI), formula (XII), formula (XIII), formula (XIV), formula (XV), or formula (XVI) of drug (D), and in some embodiments, forms a covalent bond with V of drug (D). 2 Alternatively, W forms a covalent bond with the nitrogen atom of the secondary amino group of 1 contained as a ring-constituting atom. One embodiment of the spacer unit is a self-immolative spacer unit. When CLL is cleaved, the self-immolative spacer unit decomposes by itself without undergoing further hydrolysis, releasing the free drug (D). When t is 0, no spacer unit is present, and the cleavable moiety (CLL) in vivo directly binds to the drug (D). Certain embodiments of spacer units are shown below. (23-1) Spacer unit of formula (SP-1) (In the formula, R SP is H, C 1-6 Alkyl, -OC 1-6 Alkyl, halogen, or halogenoC 1-6 is alkyl, *CLL indicates the junction with CLL. (23-2) R SP is H. The spacer unit according to (23-1). Without being bound by the following theory, it is believed that the self-immolative spacer unit used in the present invention decomposes via the following mechanism after the bond between CLL and the nitrogen atom is cleaved, thereby releasing the drug (D) (Journal of Organic Chemistry, 2002, 67, pp. 1866-1872). The linker L constituting the antibody-drug conjugate or salt thereof of the present invention A Some aspects of this are shown below. (24-1) A linker of the following formula (LA-1): *Ab indicates the Ab binding site). (24-2) A linker of the following formula (LA-2): *Ab indicates the Ab binding site). Furthermore, the linker L constituting the antibody-drug conjugate or salt thereof of the present invention A Another example is shown below: A linker of the following formula (LA-3) (see WO 2015 / 095124, wherein: *Ab indicates the binding site with Ab. A linker of the following formula (LA-4) (see WO 2015 / 095124, wherein: *Ab indicates the binding site with Ab. A linker of the following formula (LA-5) (see WO 2015 / 095223, wherein: *Ab indicates the binding site with Ab. A linker of the following formula (LA-6) (see WO 2015 / 095227, wherein: *Ab indicates the binding site with Ab. A linker of the following formula (LA-7) (see WO 2014 / 057687, wherein: *Ab indicates the binding site with Ab. A linker of the following formula (LA-8) (see WO 2013 / 173337, wherein: *Ab indicates the binding site with Ab. 3. Drug-linker conjugates (L A -D) As used herein, a "drug-linker conjugate" refers to a drug-linker conjugate that is A ) and a drug (D) are covalently bonded. The drug-linker conjugate or salt thereof of the present invention has a reactive site and can react with a functional group contained in an antibody or antigen-binding fragment (Ab) to form a covalent bond, and is useful as an intermediate for synthesizing the antibody-drug conjugate or salt thereof of the present invention. The functional group contained in Ab that forms a covalent bond with the drug-linker conjugate or salt thereof of the present invention is not particularly limited, but includes a mercapto group, an amino group, a hydroxyl group, and a carboxyl group, and in one embodiment, a mercapto group. A mercapto group that can be used to form a covalent bond with Ab can also be generated by reducing an intramolecular disulfide bond contained in Ab. For example, when the drug-linker conjugate of the present invention or a salt thereof has a maleimide structure, it reacts with a mercapto group contained in Ab to form the following partial structure, thereby synthesizing the antibody-drug conjugate of the present invention or a salt thereof (wherein Ab'-SH represents Ab having a mercapto group). Embodiments of the drug-linker conjugate or a salt thereof of the present invention are shown below. (25-1) A drug-linker conjugate represented by formula (LD-1) or a salt thereof (In the formula, D is a heterocyclic compound that induces the degradation of G12D mutant KRAS protein, R st1 is C 1-12 is alkylene, CLL is a partial structure that can be cleaved in vivo. Sp is a spacer unit that binds to CLL and D, and t is 0 or 1. (25-2) D is a heterocyclic compound represented by formula (II), A is CR A or N, R A is H, cyano, or optionally substituted C 1-３ is alkyl, Q is CR Q or N, R Q H, halogen, C 3-６ cycloalkyl, vinyl, or optionally substituted C 1-３ is alkyl, E is CH or N; R 1 is cyano, OH, halogen, and optionally substituted C 1-３ naphthyl optionally substituted with one or two groups selected from the group consisting of alkyl, or a group selected from the group consisting of the following formula (III), formula (IV) and formula (V): R 1a , R 1b and R 1c are each independently H, vinyl, halogen, or optionally substituted C 1-３ is alkyl, R 2 -V １ -V 2 or W, V 1 represents a bond, -CH2-, -O-, -S- or -N(R V1 )- and R V1 is H or optionally substituted C 1-３ is alkyl, V 2 is a group selected from the group consisting of formula (VI) and formula (VII): W is a group selected from the group consisting of the following formulas (VIII), (IX), (X), (XI), (XII), (XIII), (XIV), (XV) and (XVI): R 2a are each independently OH, OCH3, F or optionally substituted C 1-３ alkyl, and the R 2ais bonded only to a carbon atom that is a constituent atom of a ring selected from the group consisting of an azetidine ring represented by formula (VI), a pyrrolidine ring represented by formula (VII), a piperidine ring represented by formula (VIII), and a piperazine ring represented by formula (IX), m is an integer from 0 to 2, R 3 may be substituted C 1-6 alkyl, optionally substituted heterocycloalkyl, or optionally substituted heteroaryl; X is a bond, -CH2-, -O-, -S-, or -NR 4X - and R 4X is H or optionally substituted C 1-３ is alkyl, Y 1 is -O-(optionally substituted C 1-３ alkylene)- ＊Y2 , -S-(optionally substituted C 1-３ alkylene)- ＊Y2 , -SO2-(optionally substituted C 1-３ alkylene)- ＊Y2 , -NR Y -(optionally substituted C 1-３ alkylene)- ＊Y2 , -(optionally substituted C 1-３ alkylene)-O- ＊Y2 , -(optionally substituted C 1-３ Alkylene)-S- ＊Y2 , -(optionally substituted C 1-３ Alkylene)-SO2- ＊Y2 or -(optionally substituted C 1-３ (Alkylene)-NR Y - ＊Y2 And ( ＊Y2 is Y 2 ) R Y is H or optionally substituted C 1-３ is alkyl, Y 2 is a bond, optionally substituted phenylene or optionally substituted heteroarylene; LP is Y 2 and EUB, EUB is a group capable of binding to one E3 ubiquitin ligase selected from the group consisting of VHL, cereblon, IAP, MDM2, DCAF11, DCAF15, DCAF16, BIRC2, KEAP1, RNF4, RNF114, FEM1B, and AhR; CLL is a partial structure that can be cleaved in vivo. Sp is a spacer unit and binds to CLL and D, wherein Sp binds to any nitrogen atom of -NH- or oxygen atom of -OH contained in D. The drug-linker conjugate or salt thereof according to (25-1). (25-3) V 2 is a group selected from the group consisting of the following formula (VIb) and formula (VIIb): *SP indicates the bond with Sp.) W is a group selected from the group consisting of the following formulas (VIIIb), (IXb), (Xb), (XIb), (XIIb), (XIIIb), (XIVb), (XVb), and (XVIb): *SP indicates the bond with Sp.) Sp is a spacer unit and binds to CLL and D, where Sp is V 2 or nitrogen atoms contained in W ＊SP The drug-linker conjugate or salt thereof according to (25-2), which is bonded to D at a bonding site represented by (25-4) A is N, Q is CR Q and R Q is cyclopropyl, E is CH; R 1 is the following formula (III-2), R 2 But -V 1 -V 2 or W, V 1 is -N(CH3)-, V2 is the following formula (VII-2), W is represented by the following formula (XIV): R 3 is n-propyl optionally substituted with —OCH3, or tetrahydropyranyl, X is -O-, Y 1 But -O-(methylene)- ＊Y2 And ( ＊Y2 is Y 2 ) Y 2 is phenylene, L P But, Y 2 and EUB, The drug-linker conjugate or salt thereof according to (25-2), wherein EUB is a group capable of binding to an E3 ubiquitin ligase selected from the group consisting of VHL and cereblon. (25-5) V 2 is the following formula (VII-2b) ( *SP indicates the bond with Sp.) W is represented by the following formula (XIVb): *SP indicates the bond with Sp.) Sp is a spacer unit and binds to CLL and D, where Sp is V 2 or nitrogen atoms contained in W ＊SP The drug-linker conjugate or salt thereof according to (25-4), which is bonded to D at a bonding site represented by (25-6) D is, (4R)-1-[(2S)-2-(4-{4-[({6-cyclopropyl-4-[(1S,4S)-2,5-diazabicyclo[2.2.1]heptan-2-yl]-7-(6-fluoro-5-methyl-1H-indazol-4-yl)-2-[(oxan-4-yl)oxy]quinazolin-8-yl}oxy)methyl]phenyl}-1H-1,2,3-triazol-1-yl)-3-methylbutanoyl]-4-hydroxy-N-{(1R)-2-hydroxy-1-[4-(4-methyl-1,3-thiazol-5-yl)phenyl]ethyl}-L-prolinamide, (4R)-1-[(2S)-2-(4-{4-[({6-cyclopropyl-4-[(1S,4S)-2,5-diazabicyclo[2.2.1]heptan-2-yl]-7-(6-fluoro-5-methyl-1H-indazol-4-yl)-2-[(oxan-4-yl)oxy]quinazolin-8-yl}oxy)methyl]phenyl}-1H-1,2,3-triazol-1-yl)-3-methylbutanoyl]-4-hydroxy-N-{(1R)-2-hydroxy-1-[4-(2-oxo-1,3-oxazolidin-3-yl)phenyl]ethyl}-L-prolinamide, (4R)-1-[(2S)-2-(4-{4-[({6-cyclopropyl-4-[(1S,4S)-2,5-diazabicyclo[2.2.1]heptan-2-yl]-7-(6-fluoro-5-methyl-1H-indazol-4-yl)-2-[(oxan-4-yl)oxy]quinazolin-8-yl}oxy)methyl]phenyl}-1H-1,2,3-triazol-1-yl)-3-methylbutanoyl]-4-hydroxy-N-{(1R)-2-hydroxy-1-[4-(1-methyl-1H-pyrazol-5-yl)phenyl]ethyl}-L-prolinamide, (4R)-1-[(2S)-2-(4-{4-[({6-cyclopropyl-4-[(1S,4S)-2,5-diazabicyclo[2.2.1]heptan-2-yl]-7-(6-fluoro-5-methyl-1H-indazol-4-yl)-2-[(2S)-2-methoxypropoxy]quinazolin-8-yl}oxy)methyl]phenyl}-1H-1,2,3-triazol-1-yl)-3-methylbutanoyl]-4-hydroxy-N-{(1R)-2-hydroxy-1-[4-(4-methyl-1,3-thiazol-5-yl)phenyl]ethyl}-L-prolinamide, (4R)-1-[(2S)-2-(4-{4-[({6-cyclopropyl-4-[(1S,4S)-2,5-diazabicyclo[2.2.1]heptan-2-yl]-7-(6-fluoro-5-methyl-1H-indazol-4-yl)-2-[(2S)-2-methoxypropoxy]quinazolin-8-yl}oxy)methyl]phenyl}-1H-1,2,3-triazol-1-yl)-3-methylbutanoyl]-N-{(1R)-1-[4-(1-ethyl-1H-pyrazol-5-yl)phenyl]-2-hydroxyethyl}-4-hydroxy-L-prolinamide, (4R)-1-[(2S)-2-(4-{4-[({6-cyclopropyl-4-[(1S,4S)-2,5-diazabicyclo[2.2.1]heptan-2-yl]-7-(6-fluoro-5-methyl-1H-indazol-4-yl)-2-[(2S)-2-methoxypropoxy]quinazolin-8-yl}oxy)methyl]phenyl}-1H-1,2,3-triazol-1-yl)-3-methylbutanoyl]-4-hydroxy-N-{(1R)-2-hydroxy-1-[4-(4-methyl-1,3-oxazol-5-yl)phenyl]ethyl}-L-prolinamide, (4R)-1-[(2S)-2-{4-[4-({[(7M)-6-cyclopropyl-7-(6-fluoro-5-methyl-1H-indazol-4-yl)-2-[(2S)-2-methoxypropoxy]-4-{methyl[(3S)-pyrrolidin-3-yl]amino}quinazolin-8-yl]oxy}methyl)phenyl]-1H-1,2,3-triazol-1-yl}-3-methylbutanoyl]-4-hydroxy-N-{(1R)-2-hydroxy-1-[4-(4-methyl-1,3-thiazol-5-yl)phenyl]ethyl}-L-prolinamide, (4R)-1-[(2S)-2-{4-[4-({[(7M)-6-cyclopropyl-7-(6-fluoro-5-methyl-1H-indazol-4-yl)-2-[(2S)-2-methoxypropoxy]-4-{methyl[(3S)-pyrrolidin-3-yl]amino}quinazolin-8-yl]oxy}methyl)phenyl]-1H-1,2,3-triazol-1-yl}-3-methylbutanoyl]-N-{(1R)-1-[4-(1-ethyl-1H-pyrazol-5-yl)phenyl]-2-hydroxyethyl}-4-hydroxy-L-prolinamide, 3-(5-{[(3S)-4-{4-[({(7M)-6-cyclopropyl-4-[(1S,4S)-2,5-diazabicyclo[2.2.1]heptan-2-yl]-7-(6-fluoro-5-methyl-1H-indazol-4-yl)-2-[(oxan-4-yl)oxy]quinazolin-8-yl}oxy)methyl]benzoyl}-3-methylpiperazin-1-yl]methyl}-3-methyl-2-oxo-2,3-dihydro-1H-benzimidazol-1-yl)piperidine-2,6-dione, 1-(6-{[(3S)-4-{4-[({(7M)-6-cyclopropyl-4-[(1S,4S)-2,5-diazabicyclo[2.2.1]heptan-2-yl]-7-(6-fluoro-5-methyl-1H-indazol-4-yl)-2-[(oxan-4-yl)oxy]quinazolin-8-yl}oxy)methyl]benzoyl}-3-methylpiperazin-1-yl]methyl}-1-methyl-1H-indazol-3-yl)-1,3-diazinan-2,4-dione, 3-(5-{[(3S)-4-{4-[({(7M)-6-cyclopropyl-4-[(1S,4S)-2,5-diazabicyclo[2.2.1]heptan-2-yl]-7-(6-fluoro-5-methyl-1H-indazol-4-yl)-2-[(2S)-2-methoxypropoxy]quinazolin-8-yl}oxy)methyl]benzoyl}-3-methylpiperazin-1-yl]methyl}-3-methyl-2-oxo-2,3-dihydro-1H-benzimidazol-1-yl)piperidine-2,6-dione, or Dihydrogen phosphate = (2R)-2-({(4R)-1-[(2S)-2-{4-[4-({[(7M)-6-cyclopropyl-7-(6-fluoro-5-methyl-1H-indazol-4-yl)-2-[(2S)-2-methoxypropoxy]-4-{methyl[(3S)-pyrrolidin-3-yl]amino}quinazolin-8-yl]oxy}methyl)phenyl]-1H-1,2,3-triazol-1-yl}-3-methylbutanoyl]-4-hydroxy-L-prolyl}amino)-2-[4-(1H-1,2,4-triazol-1-yl)phenyl]ethyl The drug-linker conjugate or salt thereof according to (25-1), (25-7) The drug-linker conjugate or salt thereof according to (25-1), wherein formula (LD-1) is represented by formula (LD-2a) or (LD-3a): (In the formula, A is CR A or N, R A is H, cyano, or optionally substituted C 1-３ is alkyl, Q is CR Q or N, R Q H, halogen, C 3-６ cycloalkyl, vinyl, or optionally substituted C 1-３ is alkyl, E is CH or N; R 1 is cyano, OH, halogen, and optionally substituted C 1-３naphthyl optionally substituted with one or two groups selected from the group consisting of alkyl, or a group selected from the group consisting of the following formula (III), formula (IV) and formula (V): R 1a , R 1b and R 1c are each independently H, vinyl, halogen, or optionally substituted C 1-３ is alkyl, R 3 may be substituted C 1-6 alkyl, optionally substituted heterocycloalkyl, or optionally substituted heteroaryl; X is a bond, -CH2-, -O-, -S-, or -NR 4X - and R 4X is H or optionally substituted C 1-３ is alkyl, Y 1 is -O-(optionally substituted C 1-３ alkylene)- ＊Y2 , -S-(optionally substituted C 1-３ alkylene)- ＊Y2 , -SO2-(optionally substituted C 1-３ alkylene)- ＊Y2 , -NR Y -(optionally substituted C 1-３ alkylene)- ＊Y2 , -(optionally substituted C 1-３ alkylene)-O- ＊Y2 , -(optionally substituted C 1-３ Alkylene)-S- ＊Y2 , -(optionally substituted C 1-３ Alkylene)-SO2- ＊Y2 or -(optionally substituted C 1-３ (Alkylene)-NR Y - ＊Y2 And ( ＊Y2 is Y 2 ) R Y is H or optionally substituted C 1-３ is alkyl, Y 2 is a bond, optionally substituted phenylene or optionally substituted heteroarylene; L P is Y 2 and EUB, EUB is a group capable of binding to an E3 ubiquitin ligase selected from the group consisting of VHL and cereblon; R st1 is C 1-12 is alkylene, R AA are each independently H, methyl, isopropyl, benzyl, or —(CH2)3—NH—C(═O)—NH2, d is an integer from 2 to 4, and t is 0 or 1. (25-8) The drug-linker conjugate or salt thereof according to (25-1), wherein formula (LD-1) is represented by formula (LD-4a), (LD-5a), (LD-6a), (LD-7a), (LD-8a), (LD-9a), (LD-10a), (LD-11a), (LD-12a), (LD-13a), (LD-14a), or (LD-26a). (In the formula, R st1 is C 1-12 alkylene, and R AA are each independently H, methyl, isopropyl, benzyl, or —(CH 2 ) 3 —NH—C(═O)—NH 2 , d is an integer from 2 to 4, and t is 0 or 1. (25-9) The drug-linker conjugate or salt thereof according to (25-1), wherein formula (LD-1) is represented by formula (LD-15), (LD-16), (LD-17), (LD-18), (LD-19), (LD-20), (LD-21), (LD-22), (LD-23), (LD-24), (LD-25), or (LD-26). 4. Antibodies or antigen-binding fragments (Abs) The antibody or antigen-binding fragment (also referred to herein as "Ab") used in the present invention binds to an antigen protein or a modified form thereof (e.g., glycosylation) expressed on a cell surface. In one embodiment, the antibody or antigen-binding fragment used in the present invention binds to a tumor-associated antigen or cell surface receptor expressed on the surface of a cancer cell. In one embodiment, the Abs used in the present invention are selected from the group consisting of 5T4, ADAM9, ALPP, ALPPL2, AXL, B7H3, B7H4, BCMA, CA9, CCR2, CCR7, CD123, CD166, CD19, CD20, CD22, CD25, CD30, CD33, CD37, CD38, CD45, CD46, CD70, CD74, CD79b, CDH3, CDH6, CLDN1, CLDN4, CLDN6, CLDN18.2, cMET, EGFR, EphA3, FAP, FGFR3, Fibronectin, FOLRa, Globo H, GPRC5D, HER2, HER3, IGF1R, and Integrin. The antibody or antigen-binding fragment may bind to one or more antigens selected from the group consisting of αV, KAAG1, LIV1, MSLN, MT1-MMP, MUC1, MUC4, NaPi2b, Nectin4, PD-L1, PSMA, PTK7, ROR1, ROR2, SEZ6, SialylTn, TF, TROP2, TSPAN8, and VEGF. In some embodiments, Abs used in the present invention include 5T4, ADAM9, ALPP, ALPPL2, AXL, B7H3, B7H4, BCMA, CA9, CCR2, CCR7, CD123, CD166, CD19, CD20, CD22, CD25, CD30, CD33, CD37, CD38, CD45, CD46, CD70, CD74, CD79b, CDH3, CDH6, CLDN1, CLDN6, EGFR, EphA3, FAP, FGFR3, Fibronectin, FOLRa, Globo H, GPRC5D, IGF1R, and Integrin. The antibody or antigen-binding fragment binds to one or more antigens selected from the group consisting of αV, KAAG1, LIV1, MSLN, MT1-MMP, MUC4, NaPi2b, Nectin4, PD-L1, PSMA, PTK7, ROR1, ROR2, SEZ6, SialylTn, TF, and VEGF. In one embodiment, the antibody or antigen-binding fragment binds to one or more antigens selected from the group consisting of EGFR, HER2, cMET, and TROP2. In another embodiment, the antibody or antigen-binding fragment binds to EGFR. In one embodiment, the Ab used in the present invention is an anti-5T4 antibody, an anti-ADAM9 antibody, an anti-ALPP antibody, an anti-ALPPL2 antibody, an anti-AXL antibody, an anti-B7H3 antibody, an anti-B7H4 antibody, an anti-BCMA antibody, an anti-CA9 antibody, an anti-CCR2 antibody, an anti-CCR7 antibody, an anti-CD123 antibody, an anti-CD166 antibody, an anti-CD19 antibody, an anti-CD20 antibody, an anti-CD22 antibody, an anti-CD25 antibody, an anti-CD30 antibody, an anti-CD33 antibody, an anti-CD3 7 antibody, anti-CD38 antibody, anti-CD45 antibody, anti-CD46 antibody, anti-CD70 antibody, anti-CD74 antibody, anti-CD79b antibody, anti-CDH3 antibody, anti-CDH6 antibody, anti-CLDN1 antibody, anti-CLDN4 antibody, anti-C LDN6 antibody, anti-CLDN18.2 antibody, anti-cMET antibody, anti-EGFR antibody, anti-EphA3 antibody, anti-FAP antibody, anti-FGFR3 antibody, anti-Fibronectin antibody, anti-FOLRa antibody, anti-Globo It may be one or more antibodies or antigen-binding fragments thereof selected from the group consisting of H antibody, anti-GPRC5D antibody, anti-HER2 antibody, anti-HER3 antibody, anti-IGF1R antibody, anti-Integrin αV antibody, anti-KAAG1 antibody, anti-LIV1 antibody, anti-MSLN antibody, anti-MT1-MMP antibody, anti-MUC1 antibody, anti-MUC4 antibody, anti-NaPi2b antibody, anti-Nectin4 antibody, anti-PD-L1 antibody, anti-PSMA antibody, anti-PTK7 antibody, anti-ROR1 antibody, anti-ROR2 antibody, anti-SEZ6 antibody, anti-SialylTn antibody, anti-TF antibody, anti-TROP2 antibody, anti-TSPAN8 antibody, and anti-VEGF antibody.Certain embodiments of Ab used in the present invention include anti-5T4 antibody, anti-ADAM9 antibody, anti-ALPP antibody, anti-ALPPL2 antibody, anti-AXL antibody, anti-B7H3 antibody, anti-B7H4 antibody, anti-BCM A antibody, anti-CA9 antibody, anti-CCR2 antibody, anti-CCR7 antibody, anti-CD123 antibody, anti-CD166 antibody, anti-CD19 antibody, anti-CD20 antibody, anti-CD22 antibody, anti-CD25 antibody, anti-CD30 Antibodies, anti-CD33 antibodies, anti-CD37 antibodies, anti-CD38 antibodies, anti-CD45 antibodies, anti-CD46 antibodies, anti-CD70 antibodies, anti-CD74 antibodies, anti-CD79b antibodies, anti-CDH3 antibodies, anti-CDH6 antibodies, anti-CLDN1 antibodies, anti-CLDN6 antibodies, anti-EGFR antibodies, anti-EphA3 antibodies, anti-FAP antibodies, anti-FGFR3 antibodies, anti-Fibronectin antibodies, anti-FOLRa antibodies, anti-Globo The antibody is one or more antibodies or antigen-binding fragments thereof selected from the group consisting of H antibody, anti-GPRC5D antibody, anti-IGF1R antibody, anti-Integrin αV antibody, anti-KAAG1 antibody, anti-LIV1 antibody, anti-MSLN antibody, anti-MT1-MMP antibody, anti-MUC4 antibody, anti-NaPi2b antibody, anti-Nectin4 antibody, anti-PD-L1 antibody, anti-PSMA antibody, anti-PTK7 antibody, anti-ROR1 antibody, anti-ROR2 antibody, anti-SEZ6 antibody, anti-SialylTn antibody, anti-TF antibody, and anti-VEGF antibody, and in one embodiment, it is one or more antibodies or antigen-binding fragments thereof selected from the group consisting of anti-EGFR antibody, anti-HER2 antibody, anti-cMET antibody, and anti-TROP2 antibody, and in one embodiment, it is an anti-EGFR antibody or antigen-binding fragment thereof. Those skilled in the art can obtain antibodies or antigen-binding fragments thereof for use in the present invention using known methods. For example, they can be obtained by immunizing an animal with an antigenic polypeptide and collecting and purifying the antibodies produced in vivo using methods commonly used in this field. The antigen source is not limited to humans; animals can also be immunized with antigens derived from non-human animals such as mice and rats. In this case, antibodies applicable to human diseases can be selected by testing the cross-reactivity of the obtained antibodies that bind to heterologous antigens with human antigens. Alternatively, monoclonal antibodies can be obtained by establishing hybridomas by fusing antibody-producing cells that produce antibodies against antigens with myeloma cells according to known methods (e.g., Kohler and Milstein, Nature (1975) 256, pp. 495-497; Kennet, R. ed., Monoclonal Antibodies, pp. 365-367, Plenum Press, NY (1980)). The antigen to be used for immunization can be obtained, for example, by introducing a gene encoding a desired protein or polypeptide into host cells using a vector or the like, expressing the gene, and purifying the expressed protein. Alternatively, antibodies can be obtained by immunizing an animal with cells that have been genetically engineered to express a desired protein, or with cells such as a cell line that endogenously expresses the antigen. Whether an antibody or antigen-binding fragment binds to an antigen can be confirmed using known methods for measuring binding activity, such as enzyme-linked immunosorbent assay (ELISA) and flow cytometry. The antibodies or antibody-binding fragments used in the present invention may be derived from any species, including humans, rats, mice, and rabbits. If the antibodies are derived from species other than humans, they are preferably chimerized or humanized using well-known techniques. The antibodies or antibody-binding fragments used in the antibody-drug conjugates of the present invention may be polyclonal or monoclonal. In one embodiment, the Ab used in the present invention is an IgG-type antibody or antibody-binding fragment. IgG exists as subtypes, IgG1, IgG2, IgG3, and IgG4, depending on the structure of the hinge region and Fc region, and those skilled in the art can select an appropriate subtype taking into account the effector function, DAR, etc. of the antibody. In one embodiment, the Ab used in the present invention is an IgG1 or IgG4 type. In one embodiment, the Ab used in the present invention is one or more antibodies or antigen-binding fragments thereof selected from the group consisting of anti-EGFR antibodies, anti-HER2 antibodies, anti-cMET antibodies, and anti-TROP2 antibodies. In some embodiments, the Ab used in the present invention is an anti-EGFR antibody, an anti-HER2 antibody, an anti-cMET antibody, or an anti-TROP2 antibody, or an antigen-binding fragment thereof. In one embodiment, the Ab used in the present invention is an anti-EGFR antibody or an antigen-binding fragment thereof. In one embodiment, the Ab used in the present invention is an anti-HER2 antibody or an antigen-binding fragment thereof. In one embodiment, the Ab used in the present invention is an anti-TROP2 antibody or an antigen-binding fragment thereof. In one embodiment, the Ab used in the present invention is an IgG1 or IgG4 type anti-EGFR antibody, anti-HER2 antibody, or anti-TROP2 antibody. In one embodiment, the Ab used in the present invention is an anti-EGFR antibody of the IgG1 or IgG4 type. In one embodiment, the Ab used in the present invention is an anti-EGFR antibody or an antigen-binding fragment thereof comprising the heavy chain variable region and light chain variable region described in (1) or (2) below: (1) a heavy chain variable region comprising CDR1 consisting of the amino acid sequence from amino acid numbers 31 to 35 of SEQ ID NO: 1, CDR2 consisting of the amino acid sequence from amino acid numbers 50 to 65 of SEQ ID NO: 1, and CDR3 consisting of the amino acid sequence from amino acid numbers 98 to 108 of SEQ ID NO: 1; and a light chain variable region comprising a CDR1 consisting of the amino acid sequence from amino acid numbers 24 to 34 of SEQ ID NO: 2, a CDR2 consisting of the amino acid sequence from amino acid numbers 50 to 56 of SEQ ID NO: 2, and a CDR3 consisting of the amino acid sequence from amino acid numbers 89 to 97 of SEQ ID NO: 2; or (2) a heavy chain variable region comprising CDR1 consisting of the amino acid sequence of amino acids 31 to 35 of SEQ ID NO: 3, CDR2 consisting of the amino acid sequence of amino acids 50 to 65 of SEQ ID NO: 3, and CDR3 consisting of the amino acid sequence of amino acids 98 to 108 of SEQ ID NO: 3; and A light chain variable region comprising CDR1 consisting of the amino acid sequence from amino acid numbers 24 to 34 of SEQ ID NO: 4, CDR2 consisting of the amino acid sequence from amino acid numbers 50 to 56 of SEQ ID NO: 4, and CDR3 consisting of the amino acid sequence from amino acid numbers 89 to 97 of SEQ ID NO: 4. In one embodiment, the Ab used in the present invention is an anti-EGFR antibody or an antigen-binding fragment thereof comprising a heavy chain variable region and a light chain variable region selected from the group consisting of (1) to (3) below: (1) a heavy chain variable region consisting of the amino acid sequence from amino acid numbers 1 to 119 of SEQ ID NO: 1 and a light chain variable region consisting of the amino acid sequence from amino acid numbers 1 to 107 of SEQ ID NO: 2; (2) a heavy chain variable region consisting of the amino acid sequence from amino acid numbers 1 to 119 of SEQ ID NO: 3 and a light chain variable region consisting of the amino acid sequence from amino acid numbers 1 to 107 of SEQ ID NO: 4; and (3) A heavy chain variable region and a light chain variable region having at least 90% identity to the heavy chain variable region and the light chain variable region described in (1) or (2) above. In one embodiment, the Ab used in the present invention is an anti-EGFR antibody consisting of a heavy chain of SEQ ID NO:1 and a light chain of SEQ ID NO:2. The antibodies or antigen-binding fragments used in the present invention may be post-translationally modified, such as N-linked or O-linked glycosylation, N-terminal or C-terminal processing, deamidation, aspartic acid isomerization, or methionine oxidation. In the antibody or antibody-binding fragment used in the present invention, any amino acid residue may be substituted with cysteine ​​or a non-natural amino acid. Substitution with cysteine ​​can be performed using, for example, the methods described in WO2008141044 and WO2016040856. Substitution with a non-natural amino acid can be performed using, for example, the methods described in WO2010081111 and WO2013185115. The Fc region of the antibody used in the present invention may contain mutations that reduce antibody-dependent cellular cytotoxicity (ADCC) or complement-dependent cytotoxicity (CDC). L234A is a substitution of leucine with alanine at amino acid position 234 according to the EU index in the human Igγ1 constant region. L235A is a substitution of leucine with alanine at amino acid position 235 according to the EU index in the human Igγ1 constant region. The amino acid mutations L234A and L235A in the human Igγ1 constant region are referred to as "LALA mutations." This mutation is known to reduce antibody-dependent cellular cytotoxicity and complement-dependent cytotoxicity of antibodies (Mol. Immunol., 1992; Vol. 29: pp. 633-639). P331G or P331S is a substitution of proline with glycine or serine at amino acid position 331 according to the EU index in the human Igγ1 constant region. This mutation is known to reduce the CDC of the antibody (J. Immunol., 2000, Vol / 164(8), p.4178-4184). 5. Antibody-drug conjugates The antibody-drug conjugate or a salt thereof of the present invention is an antibody-drug conjugate or a salt thereof represented by the following formula (I): (In the formula, Ab is an antibody or antigen-binding fragment thereof; D is a heterocyclic compound that induces the degradation of G12D mutant KRAS protein, L A is a linker for connecting Ab and D, where n is a number between 1 and 20). n represents the drug-to-antibody ratio (DAR) in the antibody-drug conjugate, i.e., the average number of compounds bound to one antibody. In one embodiment of the antibody-drug conjugate of formula (I) or a salt thereof, n is a number from 1 to 20, in another embodiment, n is a number from 1 to 10, in another embodiment, n is a number from 2 to 8, and in another embodiment, n is a number from 2 to 5. In one embodiment of the antibody-drug conjugate of formula (I) or a salt thereof, n is a number from 1 to 6, in another embodiment, n is a number from 1 to 5, in another embodiment, n is a number from 2 to 3, in another embodiment, n is a number from 3 to 4, in another embodiment, n is a number from 4 to 5, in another embodiment, n is a number from 2 to 4, and in another embodiment, n is a number from 3 to 5. Embodiments of the antibody-drug conjugate or a salt thereof of the present invention are shown below. (26-1) An antibody-drug conjugate of formula (I) or a salt thereof (In the formula, Ab is an antibody or antigen-binding fragment thereof; D is a heterocyclic compound that induces the degradation of G12D mutant KRAS protein, L A is a linker for connecting Ab and D, where n is a number between 1 and 20). (26-2) D is a heterocyclic compound represented by formula (II), A is CR A or N, R A is H, cyano, or optionally substituted C 1-３ is alkyl, Q is CR Q or N, R Q H, halogen, C 3-６ cycloalkyl, vinyl, or optionally substituted C 1-３ is alkyl, E is CH or N; R 1 is cyano, OH, halogen, and optionally substituted C 1-３ naphthyl optionally substituted with one or two groups selected from the group consisting of alkyl, or a group selected from the group consisting of the following formula (III), formula (IV) and formula (V): R 1a , R 1b and R 1c are each independently H, vinyl, halogen, or optionally substituted C 1-３ is alkyl, R 2 -V １ -V 2 or W, V 1 represents a bond, -CH2-, -O-, -S- or -N(R V1 )- and R V1 is H or optionally substituted C 1-３ is alkyl, V 2 is a group selected from the group consisting of formula (VI) and formula (VII): W is a group selected from the group consisting of the following formulas (VIII), (IX), (X), (XI), (XII), (XIII), (XIV), (XV) and (XVI): R 2a are each independently OH, OCH3, F or optionally substituted C 1-３ alkyl, and the R 2a is bonded only to a carbon atom that is a constituent atom of a ring selected from the group consisting of an azetidine ring represented by formula (VI), a pyrrolidine ring represented by formula (VII), a piperidine ring represented by formula (VIII), and a piperazine ring represented by formula (IX), m is an integer from 0 to 2, R 3 may be substituted C 1-6 alkyl, optionally substituted heterocycloalkyl, or optionally substituted heteroaryl; X is a bond, -CH2-, -O-, -S-, or -NR 4X - and R 4X is H or optionally substituted C 1-３ is alkyl, Y 1 is -O-(optionally substituted C 1-３ alkylene)- ＊Y2 , -S-(optionally substituted C 1-３ alkylene)- ＊Y2 , -SO2-(optionally substituted C 1-３ alkylene)- ＊Y2 , -NR Y -(optionally substituted C 1-３ alkylene)- ＊Y2 , -(optionally substituted C 1-３ alkylene)-O- ＊Y2 , -(optionally substituted C 1-３ Alkylene)-S- ＊Y2 , -(optionally substituted C 1-３ Alkylene)-SO2- ＊Y2 or -(optionally substituted C 1-３ (Alkylene)-NR Y - ＊Y2 And ( ＊Y2 is Y 2 ) R Y is H or optionally substituted C 1-３ is alkyl, Y 2 is a bond, optionally substituted phenylene or optionally substituted heteroarylene; L P is Y 2 and EUB, EUB is a group capable of binding to one E3 ubiquitin ligase selected from the group consisting of VHL, cereblon, IAP, MDM2, DCAF11, DCAF15, DCAF16, BIRC2, KEAP1, RNF4, RNF114, FEM1B, and AhR; L A is a linker for connecting Ab and D, where L A is bonded to the nitrogen atom of any —NH— or the oxygen atom of any —OH included in D, or a salt thereof. (26-3) V 2 is a group selected from the group consisting of the following formula (VIa) and formula (VIIa): *LA L A ) W is a group selected from the group consisting of the following formulas (VIIIa), (IXa), (Xa), (XIa), (XIIa), (XIIIa), (XIVa), (XVa), and (XVIa): *LA L A ) L A is a linker for connecting Ab and D, where L A is V 2 or nitrogen atoms contained in W *LA The antibody-drug conjugate or salt thereof according to (26-2), wherein the antibody-drug conjugate binds to D at a binding site represented by (26-4) A is N, Q is CR Q and R Q is cyclopropyl, E is CH; R 1 is the following formula (III-2), R 2 But -V 1 -V 2 or W, V 1 is -N(CH3)-, V 2 is the following formula (VII-2), W is represented by the following formula (XIV): R 3 is n-propyl optionally substituted with —OCH3, or tetrahydropyranyl, X is -O-, Y 1 But -O-(methylene)- ＊Y2 And ( ＊Y2 is Y 2 ) Y 2 is phenylene, L P But, Y 2 and EUB, The antibody-drug conjugate or a salt thereof according to (26-2), wherein EUB is a group capable of binding to an E3 ubiquitin ligase selected from the group consisting of VHL and cereblon. (26-5) V 2 is the following formula (VII-2a) ( *LA L A ) W is represented by the following formula (XIVa): *LA L A ) L A is a linker for connecting Ab and D, where L A is V 2 or nitrogen atoms contained in W *LA The antibody-drug conjugate or salt thereof according to (26-4), wherein the antibody-drug conjugate binds to D at a binding site represented by (26-6) D is, (4R)-1-[(2S)-2-(4-{4-[({6-cyclopropyl-4-[(1S,4S)-2,5-diazabicyclo[2.2.1]heptan-2-yl]-7-(6-fluoro-5-methyl-1H-indazol-4-yl)-2-[(oxan-4-yl)oxy]quinazolin-8-yl}oxy)methyl]phenyl}-1H-1,2,3-triazol-1-yl)-3-methylbutanoyl]-4-hydroxy-N-{(1R)-2-hydroxy-1-[4-(4-methyl-1,3-thiazol-5-yl)phenyl]ethyl}-L-prolinamide, (4R)-1-[(2S)-2-(4-{4-[({6-cyclopropyl-4-[(1S,4S)-2,5-diazabicyclo[2.2.1]heptan-2-yl]-7-(6-fluoro-5-methyl-1H-indazol-4-yl)-2-[(oxan-4-yl)oxy]quinazolin-8-yl}oxy)methyl]phenyl}-1H-1,2,3-triazol-1-yl)-3-methylbutanoyl]-4-hydroxy-N-{(1R)-2-hydroxy-1-[4-(2-oxo-1,3-oxazolidin-3-yl)phenyl]ethyl}-L-prolinamide, (4R)-1-[(2S)-2-(4-{4-[({6-cyclopropyl-4-[(1S,4S)-2,5-diazabicyclo[2.2.1]heptan-2-yl]-7-(6-fluoro-5-methyl-1H-indazol-4-yl)-2-[(oxan-4-yl)oxy]quinazolin-8-yl}oxy)methyl]phenyl}-1H-1,2,3-triazol-1-yl)-3-methylbutanoyl]-4-hydroxy-N-{(1R)-2-hydroxy-1-[4-(1-methyl-1H-pyrazol-5-yl)phenyl]ethyl}-L-prolinamide, (4R)-1-[(2S)-2-(4-{4-[({6-cyclopropyl-4-[(1S,4S)-2,5-diazabicyclo[2.2.1]heptan-2-yl]-7-(6-fluoro-5-methyl-1H-indazol-4-yl)-2-[(2S)-2-methoxypropoxy]quinazolin-8-yl}oxy)methyl]phenyl}-1H-1,2,3-triazol-1-yl)-3-methylbutanoyl]-4-hydroxy-N-{(1R)-2-hydroxy-1-[4-(4-methyl-1,3-thiazol-5-yl)phenyl]ethyl}-L-prolinamide, (4R)-1-[(2S)-2-(4-{4-[({6-cyclopropyl-4-[(1S,4S)-2,5-diazabicyclo[2.2.1]heptan-2-yl]-7-(6-fluoro-5-methyl-1H-indazol-4-yl)-2-[(2S)-2-methoxypropoxy]quinazolin-8-yl}oxy)methyl]phenyl}-1H-1,2,3-triazol-1-yl)-3-methylbutanoyl]-N-{(1R)-1-[4-(1-ethyl-1H-pyrazol-5-yl)phenyl]-2-hydroxyethyl}-4-hydroxy-L-prolinamide, (4R)-1-[(2S)-2-(4-{4-[({6-cyclopropyl-4-[(1S,4S)-2,5-diazabicyclo[2.2.1]heptan-2-yl]-7-(6-fluoro-5-methyl-1H-indazol-4-yl)-2-[(2S)-2-methoxypropoxy]quinazolin-8-yl}oxy)methyl]phenyl}-1H-1,2,3-triazol-1-yl)-3-methylbutanoyl]-4-hydroxy-N-{(1R)-2-hydroxy-1-[4-(4-methyl-1,3-oxazol-5-yl)phenyl]ethyl}-L-prolinamide, (4R)-1-[(2S)-2-{4-[4-({[(7M)-6-cyclopropyl-7-(6-fluoro-5-methyl-1H-indazol-4-yl)-2-[(2S)-2-methoxypropoxy]-4-{methyl[(3S)-pyrrolidin-3-yl]amino}quinazolin-8-yl]oxy}methyl)phenyl]-1H-1,2,3-triazol-1-yl}-3-methylbutanoyl]-4-hydroxy-N-{(1R)-2-hydroxy-1-[4-(4-methyl-1,3-thiazol-5-yl)phenyl]ethyl}-L-prolinamide, (4R)-1-[(2S)-2-{4-[4-({[(7M)-6-cyclopropyl-7-(6-fluoro-5-methyl-1H-indazol-4-yl)-2-[(2S)-2-methoxypropoxy]-4-{methyl[(3S)-pyrrolidin-3-yl]amino}quinazolin-8-yl]oxy}methyl)phenyl]-1H-1,2,3-triazol-1-yl}-3-methylbutanoyl]-N-{(1R)-1-[4-(1-ethyl-1H-pyrazol-5-yl)phenyl]-2-hydroxyethyl}-4-hydroxy-L-prolinamide, 3-(5-{[(3S)-4-{4-[({(7M)-6-cyclopropyl-4-[(1S,4S)-2,5-diazabicyclo[2.2.1]heptan-2-yl]-7-(6-fluoro-5-methyl-1H-indazol-4-yl)-2-[(oxan-4-yl)oxy]quinazolin-8-yl}oxy)methyl]benzoyl}-3-methylpiperazin-1-yl]methyl}-3-methyl-2-oxo-2,3-dihydro-1H-benzimidazol-1-yl)piperidine-2,6-dione, 1-(6-{[(3S)-4-{4-[({(7M)-6-cyclopropyl-4-[(1S,4S)-2,5-diazabicyclo[2.2.1]heptan-2-yl]-7-(6-fluoro-5-methyl-1H-indazol-4-yl)-2-[(oxan-4-yl)oxy]quinazolin-8-yl}oxy)methyl]benzoyl}-3-methylpiperazin-1-yl]methyl}-1-methyl-1H-indazol-3-yl)-1,3-diazinan-2,4-dione, 3-(5-{[(3S)-4-{4-[({(7M)-6-cyclopropyl-4-[(1S,4S)-2,5-diazabicyclo[2.2.1]heptan-2-yl]-7-(6-fluoro-5-methyl-1H-indazol-4-yl)-2-[(2S)-2-methoxypropoxy]quinazolin-8-yl}oxy)methyl]benzoyl}-3-methylpiperazin-1-yl]methyl}-3-methyl-2-oxo-2,3-dihydro-1H-benzimidazol-1-yl)piperidine-2,6-dione, or Dihydrogen phosphate = (2R)-2-({(4R)-1-[(2S)-2-{4-[4-({[(7M)-6-cyclopropyl-7-(6-fluoro-5-methyl-1H-indazol-4-yl)-2-[(2S)-2-methoxypropoxy]-4-{methyl[(3S)-pyrrolidin-3-yl]amino}quinazolin-8-yl]oxy}methyl)phenyl]-1H-1,2,3-triazol-1-yl}-3-methylbutanoyl]-4-hydroxy-L-prolyl}amino)-2-[4-(1H-1,2,4-triazol-1-yl)phenyl]ethyl The antibody-drug conjugate or a salt thereof according to any one of (26-1) and (26-2), (26-7) L A is a linker represented by formula (XXVIII): (In the formula, Str is a stretcher unit that binds to Ab and CLL, and r is 0 or 1; CLL is a partial structure that can be cleaved in vivo. Sp is a spacer unit and binds to CLL and D; t is 0 or 1; *Ab indicates the Ab binding site). (26-8) The antibody-drug conjugate or salt thereof according to (26-7), wherein Str is a stretcher unit represented by formula (ST-1) and r is 1. (In the formula, R st1 may be substituted C 1-12 Alkylene, -(CH2CH2O)a1 -C 1-6 Alkylene-, -C 1-6 Alkylene-(OCH2CH2) a2 -, -Optionally substituted C 1-6 Alkylene-NH-C(=O)-optionally substituted C 1-6 Alkylene-, -optionally substituted C 1-6 Alkylene-C(=O)-NH-optionally substituted C 1-6 Alkylene-, optionally substituted C 1-6 Alkylene-C(=O)-NH-(CH2CH2O) a3 -C 1-6 Alkylene- or optionally substituted C 1-6 Alkylene-NH-C(=O)-(CH2CH2O) a4 -C 1-6 alkylene-, a1, a2, a3, and a4 are each an integer from 1 to 10, *Ab indicates the Ab binding site). (26-9) R st1 is C5 alkylene, or a salt thereof according to (26-8). (26-10) The antibody-drug conjugate or salt thereof according to (26-7), wherein CLL is a partial structure cleavable in vivo and represented by formula (CL-1): (In the formula, R AA are each independently H, methyl, isopropyl, isobutyl, sec-butyl, benzyl, p-hydroxybenzyl, hydroxymethyl, 1-hydroxyethyl, -CH2-C(=O)-OH, -(CH2)2-C(=O)-OH, -CH2-C(=O)-NH2, -(CH2)2-C(=O)-NH2, -(CH2)4-NH2, -(CH2)3-NH-C(=NH)-NH2, -(CH2)3-NH-C(=O)-NH2, -CH2-SH, or -CH2-S-CH3, or a group selected from the group consisting of the following formulae (RAA-1) and (RAA-2), d is an integer from 1 to 6, *STR indicates the binding site with Str). (26-11) RAA are each independently methyl or isopropyl, and d is 2. (26-12) R AA are each independently isopropyl or —(CH2)3—NH—C(═O)—NH2, and d is 2. (26-13) R AA are each independently H or benzyl, and d is 4. (26-14) The antibody-drug conjugate or salt thereof according to (26-7), wherein Sp is a spacer unit represented by formula (SP-1) and t is 1. (In the formula, R SP is H, C 1-6 Alkyl, -OC 1-6 Alkyl, halogen, or halogenoC 1-6 is alkyl, *CLL indicates the junction with CLL. (26-15) R SP is H. The antibody-drug conjugate or a salt thereof according to (26-14). (26-16) The antibody-drug conjugate or a salt thereof according to (26-7), wherein t is 0. (26-17) The antibody-drug conjugate or salt thereof according to (26-1), wherein formula (I) is represented by formula (AD-1a) or (AD-2a): (In the formula, Ab is an antibody or antigen-binding fragment thereof; A is CR A or N, R A is H, cyano, or optionally substituted C 1-３ is alkyl, Q is CR Q or N, R Q H, halogen, C 3-６ cycloalkyl, vinyl, or optionally substituted C 1-３ is alkyl, E is CH or N; R 1 is cyano, OH, halogen, and optionally substituted C 1-３ naphthyl optionally substituted with one or two groups selected from the group consisting of alkyl, or a group selected from the group consisting of the following formula (III), formula (IV) and formula (V): R 1a , R 1b and R 1c are each independently H, vinyl, halogen, or optionally substituted C 1-３ is alkyl, R 3 may be substituted C 1-6 alkyl, optionally substituted heterocycloalkyl, or optionally substituted heteroaryl; X is a bond, -CH2-, -O-, -S-, or -NR 4X - and R 4X is H or optionally substituted C 1-３ is alkyl, Y 1 is -O-(optionally substituted C 1-３ alkylene)- ＊Y2 , -S-(optionally substituted C 1-３ alkylene)- ＊Y2 , -SO2-(optionally substituted C 1-３ alkylene)- ＊Y2 , -NR Y -(optionally substituted C 1-３ alkylene)- ＊Y2 , -(optionally substituted C 1-３ alkylene)-O- ＊Y2 , -(optionally substituted C 1-３ Alkylene)-S- ＊Y2 , -(optionally substituted C 1-３ Alkylene)-SO2- ＊Y2 or -(optionally substituted C 1-３ (Alkylene)-NR Y - ＊Y2 And ( ＊Y2 is Y 2) R Y is H or optionally substituted C 1-３ is alkyl, Y 2 is a bond, optionally substituted phenylene or optionally substituted heteroarylene; L P is Y 2 and EUB, EUB is a group capable of binding to one E3 ubiquitin ligase selected from the group consisting of VHL, cereblon, IAP, MDM2, DCAF11, DCAF15, DCAF16, BIRC2, KEAP1, RNF4, RNF114, FEM1B, and AhR; R st1 is C 1-12 is alkylene, R AA are each independently H, methyl, isopropyl, benzyl, or —(CH)—NH—C(═O)—NH, and d is an integer from 2 to 4; t is 0 or 1, where n is a number between 1 and 20). (26-18) The antibody-drug conjugate or salt thereof according to (26-1), wherein formula (I) is represented by formula (AD-3a), (AD-4a), (AD-5a), (AD-6a), (AD-7a), (AD-8a), (AD-9a), (AD-10a), (AD-11a), (AD-12a), (AD-13a), or (AD-25a). (In the formula, R st1 is C 1-12 alkylene, and R AA are each independently H, methyl, isopropyl, benzyl, or —(CH2)3—NH—C(═O)—NH2, d is an integer from 2 to 4, t is 0 or 1, and n is a number from 1 to 20. (26-19) The antibody-drug conjugate or salt thereof according to (26-1), wherein formula (I) is represented by formula (AD-14), (AD-15), (AD-16), (AD-17), (AD-18), (AD-19), (AD-20), (AD-21), (AD-22), (AD-23), (AD-24), or (AD-25). (wherein n is a number from 1 to 20). (26-20) The antibody-drug conjugate or salt thereof according to any one of (26-1) to (26-19), wherein Ab is cetuximab and n is a number of 2 to 5. The antibody-drug conjugate of formula (I) or a salt thereof may exist in the form of a tautomer or a geometric isomer depending on the type of substituent. Although the compound of formula (I) may be described herein in only one isomeric form, the present invention also encompasses other isomers, and also encompasses isolated isomers or mixtures thereof. Furthermore, the antibody-drug conjugate of formula (I) or a salt thereof may have an asymmetric carbon atom or an asymmetric axis, and diastereomers based on this may exist. The present invention also encompasses separated diastereomers of the antibody-drug conjugate of formula (I) or a salt thereof, or a mixture thereof. Furthermore, the antibody-drug conjugate of formula (I) or a salt thereof is a pharmaceutically acceptable salt of the antibody-drug conjugate of formula (I) or a salt thereof, which may form an acid addition salt or a salt with a base depending on the type of substituent. Examples include salts described in P. Heinrich Stahl, Handbook of Pharmaceutical Salts Properties, Selection, and Use, Wiley-VCH, 2008. Specific examples include acid addition salts with inorganic acids such as hydrochloric acid, hydrobromic acid, hydroiodic acid, sulfuric acid, nitric acid, and phosphoric acid; and organic acids such as formic acid, acetic acid, propionic acid, oxalic acid, malonic acid, succinic acid, fumaric acid, maleic acid, lactic acid, malic acid, mandelic acid, tartaric acid, dibenzoyltartaric acid, ditoluoyltartaric acid, citric acid, methanesulfonic acid, ethanesulfonic acid, benzenesulfonic acid, p-toluenesulfonic acid, aspartic acid, and glutamic acid; salts with inorganic metals such as sodium, potassium, magnesium, calcium, and aluminum; salts with organic bases such as methylamine, ethylamine, and ethanolamine; salts with various amino acids and amino acid derivatives such as acetylleucine, lysine, and ornithine; and ammonium salts. Furthermore, the present invention also encompasses various hydrates and solvates, and crystalline polymorphic substances of the antibody-drug conjugate of formula (I) or a salt thereof. The present invention also encompasses all antibody-drug conjugates of formula (I) or salts thereof that are labeled with one or more pharmaceutically acceptable radioactive or non-radioactive isotopes. Examples of suitable isotopes for use in isotopic labeling of the compounds of the present invention include hydrogen ( 2 H and 3 H, etc.), carbon ( 11 C. 13 C and 14 C, etc.), nitrogen ( 13 N and 15 N, etc.), oxygen ( 15 O, 17 O and 18 O etc.), fluorine ( 18 F, etc.), chlorine ( 36 Cl, etc.), iodine ( 123 I and 125 I, etc.), sulfur ( 35 Isotopes of sulphur (e.g., sulphur) are included. It can be used for research such as tissue distribution studies of the compounds, drugs and / or substrates of the present invention labeled with isotopes. For example, tritium ( 3 H), carbon 14 ( 14 Radioisotopes such as C) may be used for this purpose because of their ease of labeling and convenience of detection. Substitution of heavier isotopes, e.g., deuterium for hydrogen ( 2 H) may be therapeutically advantageous due to increased metabolic stability (e.g., increased in vivo half-life, reduced dosage requirements, and reduced drug interactions). Positron-emitting isotopes ( 11 C, 18 F, 15 O and 13 Substitutions with 2-amino-1-methyl-2-(N, etc.) may be used in positron emission tomography (PET) studies to examine substrate receptor occupancy. The isotopically labeled compounds of the present invention can generally be produced by conventional methods known to those skilled in the art, or by a process similar to that described in the Examples or Preparations, using an appropriate isotopically labeled reagent instead of an unlabeled reagent. (Manufacturing method) The antibody-drug conjugate of formula (I) or a salt thereof can be produced by various known synthetic methods, taking advantage of characteristics based on its basic structure or the type of substituent. In this case, depending on the type of functional group, it may be effective from a manufacturing technology perspective to replace the functional group with an appropriate protecting group (a group that can be easily converted to the functional group) at the stage from the raw material to the intermediate. Examples of such protecting groups include those described in "Greene's Protective Groups in Organic Synthesis," 5th Edition, by P.G.M. Wuts and T.W. Greene, John Wiley & Sons Inc., 2014, and the like, which may be appropriately selected and used depending on the reaction conditions. In such methods, the desired compound can be obtained by introducing the protecting group, conducting the reaction, and then removing the protecting group as necessary. Hereinafter, the antibody-drug conjugate of formula (I) or a salt thereof, and the drug (D) and drug-linker conjugate (L) that constitute the antibody-drug conjugate or a salt thereof will be described. A Representative methods for producing antibodies or antigen-binding fragments (Abs) are described below. Each method can also be performed by referring to the references provided in the description. However, the production methods of the present invention are not limited to the examples shown below. In this specification, the following abbreviations may be used. DMF: N,N-dimethylformamide, DMAc: N,N-dimethylacetamide, THF: tetrahydrofuran, MeCN: acetonitrile, MeOH: methanol, EtOH: ethanol, iPrOH: isopropyl alcohol, tBuOH: tert-butyl alcohol, DOX: 1,4-dioxane, DMSO: dimethyl sulfoxide, TEA: triethylamine, DIPEA: N,N-diisopropylethylamine, tBuOK: potassium tert-butoxide, PdCl2(dppf)·CH2Cl2: [1,1'-bis(diphenylphosphino)ferrocene]palladium(II) dichloride·dichloromethane adduct, Pd / C: palladium on carbon, PyBOP: (benzotriazol-1-yloxy)tripyrrolidinophosphonium Hexafluorophosphoric acid, iPr2O: diisopropyl ether, HATU: 1-[bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-b]pyridinium 3-oxide hexafluorophosphate, DABCO: 1,4-diazabicyclo[2.2.2]octane, TFA: trifluoroacetic acid, TfOH: trifluoromethanesulfonic acid, COMU: N-[({[(1Z)-1-cyano-2-ethoxy-2-oxoethylidene]amino}oxy)(morpholin-4-yl)methylene]-N-methylmethanaminium Hexafluorophosphate, NMM: N-methylmorpholine, CDI: 1,1'-carbodiimidazole, NMO: N-methylmorpholine N-oxide, NMP: N-methyl-2-pyrrolidone, LHMDS: lithium bis(trimethylsilyl)amide, NHMDS: sodium bis(trimethylsilyl)amide, DMEDA: N,N'-dimethylethylenediamine, Triton B: benzyltrimethylammonium hydroxide, Xantphos: 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene, Ruphos: 2-dicyclohexylphosphino-2',6'-diisopropoxidephenyl, Xphos: 2-dicyclohexylphosphino-2',4',6'-triisopropylbiphenyl, BINAP: 2,2'-bis(diphenylphosphino)-1,1'-binaphthyl. I. Method for manufacturing drug (D) Drug (D) can be obtained, for example, by the methods described in International Publication Nos. 2022 / 173032, 2023 / 171781, and 2024 / 019103. A general synthesis method for drug (D) is shown below. (Drug Manufacturing Method No. 1) This method is the first method for producing the drug (D) represented by formula (II). (PG in the formula 1 -R 11 is R 1 PG is a protecting group for NH or OH contained in 1 is a group to which PG 2 -R 21 is R 2 PG is a protecting group for NH or OH contained in 2 is a group to which the following are bonded. The drug represented by formula (II) can be obtained by subjecting compound (1) to deprotection reaction conditions under acidic conditions. Examples of protecting groups that can be deprotected under acidic conditions include tert-butoxycarbonyl, triphenylmethyl, tetrahydro-2H-pyran-2-yl, methoxymethyl, dimethylmethanediyl, and tert-butylsulfinyl. This reaction is carried out by stirring an equi-equivalent or excess amount of a deprotecting reagent with compound (1) in a reaction-inert solvent under cooling to reflux, typically for 0.1 hours to 5 days. Examples of the deprotecting reagent include, but are not limited to, hydrogen chloride (DOX solution), acids such as trifluoroacetic acid, methanesulfonic acid, phosphoric acid, p-toluenesulfonic acid, and trifluoromethanesulfonic acid, and mixtures thereof. Examples of the solvent include, but are not limited to, alcohols such as MeOH and EtOH, halogenated hydrocarbons such as dichloromethane, 1,2-dichloromethane, and chloroform, ethers such as diethyl ether, THF, DOX, and dimethoxyethane, DMF, DMSO, MeCN, TfOH, water, and mixtures thereof. Furthermore, by selecting the protecting group, deprotection can also be carried out by catalytic hydrogenation or under basic conditions. Examples of protecting groups that can be deprotected by catalytic hydrogenation include benzyl, p-methoxybenzyl, and benzyloxycarbonyl groups. Deprotection can also be carried out using a fluoride ion source such as tetra-n-butylammonium fluoride. Examples of protecting groups include tert-butyl(dimethyl)silyl and (trimethylsilyl)ethoxymethyl groups. Examples of protecting groups that can be deprotected under basic conditions include acetyl, trifluoroacetyl, and benzoyl groups. PG 1 , P.G. 2 Alternatively, protecting groups that can be deprotected under different deprotection conditions may be selected and deprotection may be carried out stepwise. As references for this reaction, for example, the following can be referred to. P. G. M. Wuts and T. W. Greene, "Greene's Protective Groups in Organic Synthesis (5th ed., 2014)." When the starting compound (1) has axial chirality, the compound (1) may be separated and the resulting stereoisomer may be used to carry out this reaction. (Second Drug Manufacturing Method) This method is the second method for producing drug (D) represented by formula (II). The drug represented by formula (II) can be obtained by subjecting compound (1) to deprotection reaction conditions under acidic conditions, isolating the free form by treatment under basic conditions, and then subjecting it to salt formation reaction conditions. Examples of protecting groups that can be deprotected under acidic conditions include tert-butoxycarbonyl, triphenylmethyl, tetrahydro-2H-pyran-2-yl, methoxymethyl, dimethylmethanediyl, and tert-butylsulfinyl. In this reaction, an equivalent or excess amount of a deprotecting reagent to compound (1) is used in a reaction-inert solvent, stirred under cooling to reflux, typically for 0.1 hours to 5 days, followed by treatment with a basic aqueous solution and isolation as a free form. This is then carried out by adding an equivalent or excess amount of an acidic reagent to compound (1) in a reaction-inert solvent, stirred under cooling to reflux, typically for 0.1 hours to 5 days. Examples of deprotecting reagents used herein include, but are not limited to, hydrogen chloride (DOX solution), acids such as trifluoroacetic acid, methanesulfonic acid, phosphoric acid, p-toluenesulfonic acid, and trifluoromethanesulfonic acid, and mixtures thereof. Examples of solvents used herein include, but are not limited to, alcohols such as MeOH and EtOH, halogenated hydrocarbons such as dichloromethane, 1,2-dichloromethane, and chloroform, ethers such as diethyl ether, THF, DOX, and dimethoxyethane, DMF, DMSO, MeCN, TfOH, water, and mixtures thereof. Examples of the acidic reagent used here include hydrogen chloride (DOX solution), phosphoric acid, p-toluenesulfonic acid, etc. Examples of the basic aqueous solution used here include, but are not limited to, an aqueous sodium bicarbonate solution. Furthermore, by selecting the protecting group, deprotection can also be performed by catalytic hydrogenation or under basic conditions. Examples of protecting groups that can be deprotected by catalytic hydrogenation include benzyl, p-methoxybenzyl, and benzyloxycarbonyl. Deprotection can also be performed using a fluoride ion source such as tetra-n-butylammonium fluoride. Examples of protecting groups include tert-butyl(dimethyl)silyl and (trimethylsilyl)ethoxymethyl. Examples of protecting groups that can be deprotected under basic conditions include acetyl, trifluoroacetyl, and benzoyl. Furthermore, deprotection can be performed stepwise by selecting protecting groups that can be deprotected under different deprotection conditions as PG1 and PG2. As references for this reaction, for example, the following can be referred to. P. G. M. Wuts and T. W. Greene, "Greene's Protective Groups in Organic Synthesis (5th ed., 2014)." When the starting compound (1) has axial chirality, the compound (1) may be separated and the resulting stereoisomer may be used to carry out this reaction. (Drug raw material manufacturing method 1) This production method is a method for producing compound (1)-1, which is included in compound (1), which is the raw material for drug production methods 1 and 2. (L in the formula 2A is C 1-3 Piperidinediyl optionally substituted with alkyl, C 1-3 Piperazinediyl optionally substituted with alkyl, C 1-3 R represents pyrrolidinediyl, bridged piperazinediyl, or 2,6-diazaspiro[3.4]octanediyl, which may be substituted with alkyl; LG is C 1-12 (This indicates an alkyl group. The same applies below.) (First step) This step is a step of subjecting compound (2) to hydrolysis conditions to obtain compound (3). This reaction is carried out by using an equivalent or excess amount of a hydrolysis reagent to compound (2) in a reaction-inert solvent, typically stirring under cooling to reflux for 1 hour to 5 days. Examples of the hydrolysis reagent used here include, but are not limited to, aqueous sodium hydroxide, aqueous potassium hydroxide, aqueous lithium hydroxide, trimethyltin hydroxide, etc. Examples of the solvent include, but are not limited to, alcohols such as methanol, ethanol, and n-propanol; ethers such as tetrahydrofuran, diethyl ether, and 1,4-dioxane; halogenated hydrocarbons such as dichloromethane, 1,2-dichloroethane, and chloroform; acetonitrile; water; and mixtures thereof. (Second process) This step is a step in which compound (1)-1 is obtained by subjecting compound (3) and compound (4) to condensation reaction conditions. This reaction is carried out by adding a condensing agent and a base to a mixture of equal or equivalent amounts of compound (3) and compound (4), or an excess of one, in a reaction-inert solvent at room temperature, usually for one hour to one day. Examples of condensing agents that can be used include, but are not limited to, HATU, 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide or its hydrochloride, dicyclohexylcarbodiimide, 1,1'-carbonyldiimidazole, COMU, and PyBOP. Examples of bases include, but are not limited to, organic bases such as triethylamine, N,N-diisopropylethylamine, and pyridine, and inorganic bases such as potassium carbonate, sodium carbonate, and cesium carbonate. Examples of the solvent include, but are not limited to, halogenated hydrocarbons such as dichloromethane, 1,2-dichloroethane, and chloroform; ether solvents such as tetrahydrofuran, diethyl ether, and 1,4-dioxane; alcohols such as methanol, ethanol, and n-propanol; N,N-dimethylformamide; and mixtures thereof. (Drug raw material manufacturing method 2) This production method is the first method for producing compound (2)-1, which is included in compound (2), the raw material of Drug Raw Material Production Method 1. (In the formula, PG 3 is the protecting group for OH, LG 1 represents a leaving group, and BLG represents a boronic acid group, a boronic acid group protected by a boronic acid protecting group such as a boronic acid pinacol ester group, or a trifluoroborate group (hereinafter, sometimes referred to as a boronic acid group, etc.). Examples of leaving groups shown here include Cl, Br, a methanesulfonyloxy group, a p-toluenesulfonyloxy group, etc. (The same applies below.) (First step) This step is a method for producing compound (7) by ipso substitution reaction between compound (5)-1 and compound (6)-1. This reaction involves using equimolar amounts of compound (5)-1 and compound (6)-1, or an excess of one of them. The resulting mixture is stirred in a reaction-inert solvent, or without solvent, under cooling to reflux, preferably at 0°C to 120°C, for typically 0.1 hours to 5 days. Examples of solvents that can be used include, but are not limited to, halogenated hydrocarbons such as dichloromethane, 1,2-dichloroethane, and chloroform; aromatic hydrocarbons such as benzene, toluene, and xylene; ethers such as diethyl ether, THF, dehydrated THF, DOX, and 1,2-dimethoxyethane; DMF, DMAc, DMSO, ethyl acetate, MeCN, NMP, and mixtures thereof. It may be advantageous to carry out the reaction in the presence of an organic base such as TEA, DIPEA, NMM, DABCO, or tBuOK, or an inorganic base such as sodium hydride, potassium carbonate, sodium carbonate, or cesium carbonate, in order to ensure smooth reaction progress. Furthermore, the compound (7) can be produced by catalytic hydrogenation of the compound obtained by the Mizoroki-Heck reaction of the compound (5)-1 with the compound (6)-1. [Literature] Chem. Rev., 2003, 103, p.2945-2964 (Second process) This step is a method for producing compound (9) by ipso substitution reaction between compound (7) and compound (8). The reaction conditions are the same as those in the first step of Drug Substance Preparation Method 2. Furthermore, compound (9) can be produced by Negishi coupling of compound (8) in which the hydrogen atom is converted to a halogen atom with compound (7). [Literature] ACC. Chem. Res., 1982, 15, p.340-348 (Third step) This process involves the reaction of compound (9) with PG 3 This is a method for producing compound (10)-1 by an ipso substitution reaction with —OH. The PG used here 3 Examples of -OH include benzyl alcohol, p-methoxybenzyl alcohol, and 1-phenylethanol. The reaction conditions are the same as those in the first step of Drug Substance Preparation Method 2. (Fourth step) This step is carried out by reacting compound (10) containing both compound (10)-1 obtained in the third step of this synthesis method and compound (10)-2 obtained in the third step of the drug raw material production method 9 described later with R Ｑ This method involves the Suzuki-Miyaura coupling reaction with a boronic acid derivative comprising a boronic acid group or the like to produce compound (11). Examples of the boronic acid group or the like used here include, but are not limited to, a boronic acid group, a boronic acid ester group, a boronic acid pinacol ester group, a triolborate base, and a trifluoroborate base. This reaction is carried out by reacting compound (10) with R ＱA mixture of these compounds is stirred in the presence of a base and a palladium catalyst in a reaction-inert solvent at room temperature to reflux, preferably at 20°C to 140°C, for typically 0.1 hours to 5 days. Examples of solvents that can be used include, but are not limited to, halogenated hydrocarbons such as dichloromethane, 1,2-dichloroethane, and chloroform; aromatic hydrocarbons such as benzene, toluene, and xylene; ethers such as diethyl ether, THF, DOX, and 1,2-dimethoxyethane; alcohols such as MeOH, EtOH, isopropyl alcohol, butanol, and amyl alcohol; DMF, DMSO, MeCN, 1,3-dimethylimidazolidin-2-one, water, and mixtures thereof. Examples of bases include inorganic bases such as tripotassium phosphate, sodium carbonate, potassium carbonate, sodium hydroxide, barium hydroxide, and cesium carbonate. Examples of the palladium catalyst include tetrakis(triphenylphosphine)palladium, bis(triphenylphosphine)palladium(II) dichloride, [1,1'-bis(diphenylphosphino)ferrocene]palladium(II) dichloride-dichloromethane adduct, (1E,4E)-1,5-diphenylpenta-1,4-dien-3-one / palladium (3:2), (2-dicyclohexylphosphino-2',6'-diisopropoxy-1,1'-biphenyl)[2-(2'-amino-1,1'-biphenyl)]palladium(II) methanesulfonate, palladium(II) acetate, and mesyl[(tri-tert-butylphosphine)-2-(2-aminobiphenyl)]palladium(II). In some cases, it may be advantageous to carry out the reaction in the presence of a ligand such as dicyclohexyl(2',6'-dimethoxybiphenyl-2-yl)phosphine, dicyclohexyl(2',6'-diisopropoxy-[1,1'-biphenyl]-2-yl)phosphine, 1,1'-bis(diphenylphosphino)ferrocene, butyldi-1-adamantylphosphine, or di(adamantan-1-yl)(butyl)phosphine in order to ensure smooth progress of the reaction.Alternatively, the precatalyst (2-dicyclohexylphosphino-2',6'-diisopropoxy-1,1'-biphenyl)[2-(2'-amino-1,1'-biphenyl)]palladium(II) can be used as a palladium catalyst for this reaction. Microwave heating of the mixture may be beneficial for smooth reaction progression. [Literature] J. Am. Chem. Soc., 2005, 127, p.4685-4696 Org. Lett. 2011, 13, p.3948-3951 Org. Lett. 2012, 14, p.1278-1281 Compound (10) is deiodinated using a Pd catalyst and a reducing agent to give compound (11) (where R Ｑ can produce hydrogen). [Literature] J. Org. Chem., 1977, 42, p.3491-3494 Tetrahedron Letters 2013, 54, 5207-5210 (Fifth step) This step is a method for producing compound (13) by Suzuki-Miyaura coupling reaction between compound (11) and compound (12). The reaction conditions are the same as those in the fourth step of Drug Substance Preparation Method 2. Compound (13) may have axial chirality and may be obtained as a mixture of stereoisomers. １ Compound (13) in which is a protecting group or a compound obtained by deprotecting compound (13) (e.g., compound (14)) can be subjected to a conventional resolution procedure, for example, resolution using ODS column chromatography or silica gel column chromatography, to isolate each stereoisomer. (Sixth step) This step is a method for producing compound (14) by deprotecting compound (13) through catalytic hydrogenation. This reaction can be carried out by stirring compound (13) under a hydrogen atmosphere in a reaction-inert solvent such as MeOH, EtOH, or ethyl acetate under normal to elevated pressure in the presence of a metal catalyst, with stirring for 1 hour to 5 days, from cooling to heating, preferably at room temperature. Examples of the metal catalyst include palladium catalysts such as Pd / C or palladium black, platinum catalysts such as platinum plate or platinum oxide, and nickel catalysts such as reduced nickel or Raney nickel. PG １ When a tetrahydro-2H-pyran-2-yl group or the like is used as a protecting group of (I), a base may be used to suppress deprotection. Examples of the base used here include, but are not limited to, sodium bicarbonate, sodium carbonate, potassium carbonate, cesium carbonate, etc. Compound (14) may have axial chirality and may be obtained as a mixture of stereoisomers. １ Compound (14) in which is a protecting group or a compound obtained by subjecting compound (14) to a deprotection reaction can be subjected to a conventional resolution procedure, for example, resolution using ODS column chromatography or silica gel column chromatography, to isolate each stereoisomer. As references for this reaction, for example, the following can be referred to. Chemical Society of Japan, "Experimental Chemistry Lectures," 5th edition, Vol. 13, Maruzen, 2004 (Seventh step) This step is a method for producing compound (2)-1 by reacting compound (14) with compound (15). This reaction is carried out by reacting a mixture of equal amounts of compound (14) and compound (15), or an excess of either, in the presence of a base in a reaction-inert solvent under cooling to reflux, preferably at 0°C to 80°C, for typically 0.1 hours to 5 days. Examples of solvents used include, but are not limited to, aromatic hydrocarbons such as benzene, toluene, and xylene; alcohols such as MeOH and EtOH; ethers such as diethyl ether, THF, DOX, and 1,2-dimethoxyethane; halogenated hydrocarbons such as dichloromethane, 1,2-dichloroethane, and chloroform; DMF, DMSO, ethyl acetate, MeCN, and mixtures thereof. Examples of bases include, but are not limited to, organic bases such as TEA, DIPEA, 1,8-diazabicyclo[5.4.0]-7-undecene, n-butyllithium, and tBuOK; and inorganic bases such as sodium hydroxide, sodium carbonate, potassium carbonate, cesium carbonate, and sodium hydride. It may be advantageous to carry out the reaction in the presence of a phase transfer catalyst such as tetra-n-butylammonium chloride. As references for this reaction, for example, the following can be referred to. Chemical Society of Japan, "Experimental Chemistry Lectures," 5th edition, Vol. 14, Maruzen, 2005 Compound (2)-1 may have axial chirality and may be obtained as a mixture of stereoisomers. １ The compound (2)-1 in which is a protecting group or the compound obtained by subjecting the compound (2)-1 to a deprotection reaction can be subjected to a conventional resolution procedure, for example, resolution using ODS column chromatography or silica gel column chromatography, to isolate each stereoisomer. Furthermore, compound (15) can be prepared by the reaction of LG 1 The compound having a hydroxy group in the corresponding position is sulfonylated in the presence of a base to give LG 1is a sulfonyloxy group. Examples of the sulfonylation reagent used here include, but are not limited to, methanesulfonyl chloride, p-toluenesulfonyl chloride, methanesulfonic anhydride, etc. Examples of the base include, but are not limited to, TEA, DIPEA, pyridine, tetramethylethylenediamine, etc. As references for this reaction, for example, the following can be referred to. Synthesis 1999, 9, p.1633-1636 (Drug Raw Material Manufacturing Method 3) This production method is the second method for producing compound (2)-1, which is included in compound (2), the raw material of Drug Raw Material Production Method 1. (wherein q represents 1 or 2, the same applies hereinafter) (First step) This step involves the reaction of compound (7) with R LG This method is a method for producing compound (16) by ipso substitution reaction with —SH. LG An example of -SH is C 1-12 Alkyl thiols such as ethanethiol and dodecanethiol are included. The reaction conditions are the same as those in the first step of Drug Substance Preparation Method 2. (Second process) This step involves the reaction of compound (16) with PG 3 This method produces compound (17)-1 by ipso substitution reaction with —OH. 3 Examples of -OH include benzyl alcohol, p-methoxybenzyl alcohol, and 1-phenylethanol. The reaction conditions are the same as those in the first step of Drug Substance Preparation Method 2. (Third step) This step is carried out to synthesize compound (17)-1 obtained in the second step of this synthesis method and compound (17)-2 obtained in the fourth step of the drug raw material production method 8 described later, and R ＱThis is a method for producing compound (18) by Suzuki-Miyaura coupling reaction with a boronic acid derivative comprising a -boronic acid group or the like. The reaction conditions are the same as those in the fourth step of Drug Substance Preparation Method 2. Compound (17) is deiodinated using a Pd catalyst and a reducing agent to give compound (18) (wherein R Ｑ can produce hydrogen). [Literature] J. Org. Chem., 1977, 42, p.3491-3494 Tetrahedron Letters 2013, 54, 5207-5210 (Fourth step) This step is a method for producing compound (19) by Suzuki-Miyaura coupling reaction between compound (18) and compound (12). The reaction conditions are the same as those in the fourth step of Drug Substance Preparation Method 2. Although compound (19) may have axial chirality and may be obtained as a mixture of stereoisomers, each stereoisomer of compound (19) can be isolated by a conventional resolution procedure, for example, resolution using ODS column chromatography or silica gel column chromatography. Alternatively, compound (19) can be deprotected to isolate the stereoisomers, and then reprotected with a protecting group to isolate the stereoisomers of compound (19). Examples of the protecting group for reprotection include a tetrahydro-2H-pyran-2-yl group. (Fifth step) This step is a method for producing compound (20) by oxidation of compound (19). In this reaction, compound (19) is treated with an equivalent or excess equivalent of an oxidizing agent in a reaction-inert solvent under cooling to heating, preferably at -20°C to 80°C, typically for 0.1 hours to 3 days. In this reaction, oxidation using m-chloroperbenzoic acid, perbenzoic acid, peracetic acid, sodium hypochlorite, or hydrogen peroxide is preferably used. Examples of solvents include aromatic hydrocarbons such as benzene and toluene, ethers such as THF, halogenated hydrocarbons such as chloroform and dichloromethane, DMF, DMSO, ethyl acetate, MeCN, and mixtures thereof. Examples of other oxidizing agents include cumene hydroperoxide, oxone, activated manganese dioxide, chromic acid, potassium permanganate, and sodium periodate. [Literature] Chemical Society of Japan, "Experimental Chemistry Lectures," 5th edition, Vol. 17, Maruzen, 2004 (Sixth step) This step is a method for producing compound (13) by an ipso substitution reaction between compound (20) and compound (8). The reaction conditions are the same as those in the first step of Drug Substance Preparation Method 2. When compound (13) has axial chirality, it is obtained as a mixture of stereoisomers, but each stereoisomer can be isolated by a conventional resolution procedure, for example, resolution using ODS column chromatography or silica gel column chromatography. (Seventh step) This step is a method for producing compound (14) by deprotecting compound (13) through catalytic hydrogenation. The reaction conditions are the same as those in the sixth step of Drug Substance Preparation Method 2. Compound (14) may have axial chirality and may be obtained as a mixture of stereoisomers. However, compound (14) can be resolved into individual stereoisomers by a conventional resolution procedure, for example, by ODS column chromatography or silica gel column chromatography. (Eighth process) This step is a method for producing compound (2)-1 by reacting compound (14) with compound (15). The reaction conditions are the same as those in the seventh step of Drug Substance Preparation Method 2. Although compound (2)-1 may have axial chirality and may be obtained as a mixture of stereoisomers, each stereoisomer of compound (2)-1 can be isolated by a conventional resolution procedure, for example, resolution using ODS column chromatography or silica gel column chromatography. Alternatively, compound (2)-1 can be deprotected to isolate the stereoisomers, and then reprotected with a protecting group to isolate the stereoisomers. Examples of the protecting group for reprotection include a tetrahydro-2H-pyran-2-yl group. (Drug Raw Material Manufacturing Method 4) This production method is the third method for producing compound (2)-1, which is included in compound (2), the raw material of Drug Raw Material Production Method 1. (First step) This step is a method for producing compound (21) by deprotecting compound (20) through catalytic hydrogenation. The reaction conditions are the same as those in the sixth step of Drug Substance Preparation Method 2. Compound (21) may have axial asymmetry and may be obtained as a mixture of stereoisomers. However, compound (21) can be resolved into individual stereoisomers by a conventional resolution procedure, for example, by ODS column chromatography or silica gel column chromatography. (Second process) This step is a method for producing compound (22) by alkylation reaction of compound (21) with compound (15). The reaction conditions are the same as those in the seventh step of Drug Substance Preparation Method 2. Although compound (22) may have axial chirality and may be obtained as a mixture of stereoisomers, each stereoisomer of compound (22) can be isolated by a conventional resolution procedure, for example, resolution using ODS column chromatography or silica gel column chromatography. Alternatively, compound (22) can be deprotected to isolate the stereoisomers, and then reprotected with a protecting group to isolate the stereoisomers of compound (22). Examples of the protecting group for reprotection include a tetrahydro-2H-pyran-2-yl group. (Third step) This step is a method for producing compound (2)-1 by the ipso substitution reaction of compound (22) with compound (8). The reaction conditions are the same as those in the first step of Drug Substance Preparation Method 2. Compound (2)-1 may have axial chirality and is obtained as a mixture of stereoisomers. However, compound (2)-1 or a compound obtained by subjecting compound (2)-1 to a deprotection reaction can be resolved by a conventional resolution procedure, for example, using ODS column chromatography or silica gel column chromatography, to isolate the individual stereoisomers. The reaction conditions for the deprotection reaction used here are the same as those in the step described in Production Method 1. (Drug Raw Material Manufacturing Method 5) This production method is the first method for producing compound (2)-2, which is included in compound (2), the raw material of drug raw material production method 1. (PG in the formula 22 indicates a tert-butyl group. The same applies below.) (First step) This step is a method for producing compound (23) by hydrolyzing compound (5)-1. This reaction is carried out by using equal amounts of compound (5)-1 and a hydrolysis reagent, or an excess of one, in a reaction-inert solvent, stirring under cooling to reflux for typically 0.1 hours to 5 days. Examples of the solvent used here include, but are not limited to, alcohols such as methanol and ethanol, acetone, DMF, and THF. Mixing the above solvents with water may also be suitable for the reaction. Examples of the hydrolysis reagent include, but are not limited to, aqueous sodium hydroxide, aqueous potassium hydroxide, sodium hydroxide, potassium hydroxide, and lithium hydroxide. As references for this reaction, for example, the following can be referred to. "Experimental Chemistry Lectures (5th Edition)" edited by the Chemical Society of Japan, Vol. 16 (2005) (Maruzen) Angew. Chem. Int. Ed. 2005, 44, p.1378-1382. (Second process) This step is a method for producing compound (24) by protecting the hydroxyl group of compound (23) with a tert-butyl group. This reaction is carried out by stirring the compound (23) and a tert-butyl protecting reagent in equimolar amounts or in an excess of one in a reaction-inert solvent under cooling to reflux, typically for 0.1 hours to 5 days. Examples of solvents that can be used include, but are not limited to, ethers such as THF and DOX, halogenated hydrocarbons such as dichloromethane, tBuOH, and DMF. Examples of tert-butyl protecting reagents include, but are not limited to, isobutene and 2-tert-butyl-1,3-diisopropylisourea. Alternatively, compound (24) can be produced by a dehydration condensation reaction of compound (23) with tBuOH. As references for this reaction, for example, the following can be referred to. PGM Wuts and TW Greene, "Greene's Protective Groups in Organic Synthesis," 5th ed., John Wiley & Sons Inc., 2014 Org. Lett., 2012, 14, 17, p.4678-4681 (Third step) This step involves the reaction of compound (24) with R LG This method involves the production of compound (25) by ipso substitution reaction with -SH. The reaction conditions are the same as those in the first step of Drug Substance Preparation Method 2. (Fourth step) This process involves the reaction of compound (25) with PG 3 This method involves the production of compound (26) by ipso substitution reaction with —OH. The reaction conditions are the same as those in the first step of Drug Substance Preparation Method 2. (Fifth step) This step involves the reaction of compound (26) with R Q This is a method for producing compound (27) by Suzuki-Miyaura coupling reaction with a boronic acid derivative comprising a -boronic acid group or the like. The reaction conditions are the same as those in the fourth step of Drug Substance Preparation Method 2. Compound (26) is deiodinated using a Pd catalyst and a reducing agent to give compound (27) (where R Q can produce hydrogen). [Literature] J. Org. Chem., 1977, 42, p.3491-3494 Tetrahedron Letters 2013, 54, 5207-5210 (Sixth step) This step is a method for producing compound (28) by Suzuki-Miyaura coupling reaction between compound (27) and compound (12). The reaction conditions are the same as those in the fourth step of Drug Substance Preparation Method 2. Although compound (28) may have axial chirality and may be obtained as a mixture of stereoisomers, each stereoisomer of compound (28) can be isolated by a conventional resolution procedure, for example, resolution using ODS column chromatography or silica gel column chromatography. Alternatively, compound (28) can be deprotected to isolate the stereoisomers, and then reprotected with a protecting group to isolate the stereoisomers of compound (28). Examples of the protecting group for reprotection include a tetrahydro-2H-pyran-2-yl group. (Seventh step) This step is a method for producing compound (29) by oxidation of compound (28). The reaction conditions are the same as those in the fifth step of Drug Substance Preparation Method 3. As references for this reaction, for example, the following can be referred to. PGM Wuts and TW Greene, "Greene's Protective Groups in Organic Synthesis," 5th ed., John Wiley & Sons Inc., 2014 (Eighth process) This step is a method for producing compound (30) by an ipso substitution reaction between compound (29) and compound (8). The reaction conditions are the same as those in the first step of Drug Substance Preparation Method 2. (Ninth step) This step is a method for producing compound (31) by deprotecting compound (30) through catalytic hydrogenation. The reaction conditions are the same as those in the sixth step of Drug Substance Preparation Method 2. Compound (31) may have axial asymmetry and may be obtained as a mixture of stereoisomers. However, compound (31) can be resolved into individual stereoisomers by a conventional resolution procedure, for example, by ODS column chromatography or silica gel column chromatography. (10th step) This step is a method for producing compound (32) by alkylation reaction of compound (31) with compound (15). The reaction conditions are the same as those in the seventh step of Drug Substance Preparation Method 2. Although compound (32) may have axial chirality and may be obtained as a mixture of stereoisomers, each stereoisomer of compound (32) can be isolated by a conventional resolution procedure, for example, resolution using ODS column chromatography or silica gel column chromatography. Alternatively, compound (32) can be deprotected to isolate the stereoisomers, and then reprotected with a protecting group to isolate the stereoisomers of compound (32). (Eleventh step) This step is a method for producing compound (33) by subjecting compound (32) to a deprotection reaction. The reaction conditions are the same as those described in the first drug production process. After deprotection, compound (33) can be reprotected with a protecting group, such as a tetrahydro-2H-pyran-2-yl group. Alternatively, the above series of deprotection and reprotection with a protecting group may be carried out as a one-step reaction. (Twelfth step) This step is a method for producing compound (2)-2 by reacting compound (33) with compound (6)-1. This reaction involves using equimolar amounts of compound (33) and compound (6)-1, or an excess of either compound, and stirring the mixture in the presence of a condensing agent in a reaction-inert solvent under cooling to heating, preferably at temperatures between -20°C and 60°C, for typically 0.1 hours to 5 days. Examples of solvents include, but are not limited to, aromatic hydrocarbons such as benzene and toluene, ethers such as THF and DOX, halogenated hydrocarbons such as chloroform and dichloromethane, alcohols such as methanol and ethanol, DMF, DMSO, ethyl acetate, MeCN, and mixtures thereof. Examples of condensing agents include PyBOP, HATU, and CDI. Carrying out the reaction in the presence of an organic base such as TEA, DIPEA, or NMM, or an inorganic base such as potassium carbonate, sodium carbonate, or cesium carbonate, may be advantageous for smooth reaction progression. (Drug Raw Material Manufacturing Method 6) This method is a method for producing compound (13)-1, which is included in compound (13), an intermediate of drug raw material production method 2. (First step) This step is a method for producing compound (34) by subjecting compound (30) to a deprotection reaction. The reaction conditions are the same as those described in the first drug production process. After deprotection, compound (34) can be reprotected with a protecting group, such as a tetrahydro-2H-pyran-2-yl group. Alternatively, the above series of deprotection and reprotection with a protecting group may be carried out as a one-step reaction. (Second process) This step is a method for producing compound (13)-1 by reacting compound (34) with compound (6)-1. The reaction conditions are the same as those in the twelfth step of Drug Substance Preparation Method 5. (Drug Raw Material Manufacturing Method 7) This production method is a method for producing compound (30), which is a raw material for Drug Raw Material Production Method 6. (First step) This step is a method for producing compound (37) by ipso substitution reaction between compound (24) and compound (8). The reaction conditions are the same as those in the first step of Drug Substance Preparation Method 2. (Second process) This step involves the reaction of compound (37) with PG 3 This is a method for producing compound (38) by ipso substitution reaction with —OH. The reaction conditions are the same as those in the first step of Drug Substance Preparation Method 2. (Third step) This step involves the reaction of compound (38) with R Ｑ This is a method for producing compound (39) by Suzuki-Miyaura coupling reaction with a boronic acid derivative comprising a -boronic acid group or the like. The reaction conditions are the same as those in the fourth step of Drug Substance Preparation Method 2. Compound (38) is dehalogenated using a Pd catalyst and a reducing agent to give compound (39) (where R Qcan produce hydrogen). [Literature] J. Org. Chem., 1977, 42, p.3491-3494 Tetrahedron Letters 2013, 54, 5207-5210 (Fourth step) This step is a method for producing compound (30) by Suzuki-Miyaura coupling reaction between compound (39) and compound (15). The reaction conditions are the same as those in the fourth step of Drug Substance Preparation Method 2. Although compound (30) may have axial chirality and may be obtained as a mixture of stereoisomers, each stereoisomer of compound (30) can be isolated by a conventional resolution procedure, for example, resolution using ODS column chromatography or silica gel column chromatography. Alternatively, compound (30) can be deprotected to isolate the stereoisomers, and then reprotected with a protecting group to isolate the stereoisomers of compound (30). (Drug Raw Material Manufacturing Method 8) This production method is a method for producing compound (17)-2, which is included in compound (17), an intermediate in Drug Raw Material Production Method 3. (First step) This step is a method for producing compound (5)-2 by chlorination of compound (40). This reaction is carried out by stirring a mixture of compound (40) and a chlorinating agent in equimolar amounts or in an excess of one in an inert solvent, either in the presence of a solvent or without a solvent, under cooling to reflux, preferably at 60°C to reflux, for typically 0.1 hours to 5 days. Examples of solvents used herein include, but are not limited to, aromatic hydrocarbons such as toluene, ethers such as THF and DOX, halogenated hydrocarbons such as dichloromethane, DMF, and DMAc. Examples of chlorinating agents include phosphorus oxychloride and thionyl chloride. Carrying out the reaction in the presence of an organic base such as TEA, DIPEA, or NMM may be advantageous for smooth reaction progression. (Second process) In this step, compound (5)-2 and R LG This is a method for producing compound (41) by ipso substitution reaction with —SH. The reaction conditions are the same as those in the first step of Drug Substance Preparation Method 2. (Third step) This step involves the reaction of compound (41) with PG 3 This is a method for producing compound (42) by ipso substitution reaction with —OH. The reaction conditions are the same as those in the first step of Drug Substance Preparation Method 2. (Fourth step) This step is a method for producing compound (17)-2 by the ipso substitution reaction of compound (42) with compound (6)-1. The reaction conditions are the same as those in the first step of Drug Substance Preparation Method 2. (Drug Raw Material Manufacturing Method 9) This production method is a method for producing compound (10)-2. (First step) This step is a method for producing compound (43) by the ipso substitution reaction of compound (5)-2 with compound (8). The reaction conditions are the same as those in the first step of Drug Substance Preparation Method 2. Furthermore, compound (43) can be produced by Negishi coupling of compound (8) in which the hydrogen atoms are converted to halogens with compound (5)-2. (Second process) This step involves the reaction of compound (43) with PG 3 This is a method for producing compound (44) by ipso substitution reaction with —OH. The reaction conditions are the same as those in the first step of Drug Substance Preparation Method 2. (Third step) This step is a method for producing compound (10)-2 by the ipso substitution reaction of compound (44) with compound (6)-1. The reaction conditions are the same as those in the first step of Drug Substance Preparation Method 2. (Drug Raw Material Manufacturing Method 10) This production method is a method for producing compound (4)-1, which is included in compound (4), which is an intermediate in Drug Raw Material Production Method 1. (In the formula, L２Ｂ is C 1-3 Piperazinediyl optionally substituted with alkyl, bridged piperazinediyl, or 2,6-diazaspiro[3.4]octanediyl; PG E3 and P.G. L２ is the protecting group for NH, LG Z represents a leaving group, and BLG represents a boronic acid group, a boronic acid group protected by a boronic acid protecting group such as a boronic acid pinacol ester group, or a trifluoroborate group (hereinafter, sometimes referred to as a boronic acid group, etc.). E3 Compound (4)-1 can be produced by a similar reaction for compounds in which the moiety is H. Examples of leaving groups shown here include Cl, Br, a methanesulfonyloxy group, a p-toluenesulfonyloxy group, etc. (The same applies below.) (First step) This step is a step in which compound (47) is obtained by subjecting compound (45) and compound (46) to Suzuki-Miyaura coupling reaction conditions. The reaction conditions are the same as those in the fourth step of Drug Substance Preparation Method 2. (Second step-1A) This step is a step of subjecting compound (47) to oxidation reaction conditions to obtain a 1,2-diol compound. This reaction is carried out by stirring compound (47), an oxidizing agent, and an excess equivalent of a reoxidizing agent in a reaction-inert solvent at ice-cooling to room temperature for typically 1 hour to 2 days. Examples of oxidizing agents include, but are not limited to, osmium(VIII) tetroxide, PI osmium(VIII) oxide, and PEM polymer-microencapsulated osmium(VIII) oxide. Examples of reoxidizing agents include, but are not limited to, NMO, trimethylamine oxide, tert-butyl hydroperoxide (tBuOOH), KFe(CN) and the like. Examples of solvents include, but are not limited to, ethers such as tetrahydrofuran, diethyl ether, and 1,4-dioxane; halogenated hydrocarbons such as dichloromethane, dichloroethane, and chloroform; tBuOH; acetone; acetonitrile; toluene; water; and mixtures thereof. (Second step-1B) This step is a step of subjecting the compound obtained in the above (Second Step-1A) to oxidative cleavage reaction conditions to obtain compound (48). This reaction is carried out by using an oxidizing agent in an equivalent or excess amount to the compound obtained in (Second Step-1A) in a reaction-inert solvent, stirring at ice-cooling to room temperature for typically 1 hour to 2 days. Examples of the oxidizing agent used here include, but are not limited to, sodium periodate or periodic acid. Examples of the solvent used here include, but are not limited to, ether solvents such as tetrahydrofuran, diethyl ether, and 1,4-dioxane; acetonitrile; water; halogenated hydrocarbons such as dichloromethane, dichloroethane, and chloroform; and mixtures thereof. The above (Second Step-1A) and (Second Step-1B) can also be carried out as a one-step reaction. [Literature] J. Org. Chem. 1956, 21, 4, 478-479 (Second step-2) This step is a step of obtaining compound (48) by subjecting compound (47) to oxidation reaction conditions. This step is a method of obtaining compound (48) by a method different from Second Step-1A and Second Step-1B. In this reaction, compound (47) is stirred in an ozone atmosphere in a reaction-inert solvent at ice-cooling to room temperature for typically 1 hour to 1 day, followed by treatment with a reducing agent. Examples of the reducing agent used here include, but are not limited to, dimethyl sulfide, triphenylphosphine, and metallic zinc. Examples of the solvent used here include, but are not limited to, alcoholic solvents such as methanol and ethanol, halogenated hydrocarbons such as dichloromethane, dichloroethane, and chloroform, ethyl acetate, and mixtures thereof. (Third step) In this step, compound (4)-1' is obtained by subjecting compound (48) and compound (49) to reductive amination reaction conditions. This reaction is carried out by using equal amounts of compound (48) and compound (49), or an excess of one, in the presence of a reducing agent and acetic acid, in a reaction-inert solvent, stirring at ice-cooling to room temperature for typically 1 hour to 5 days. Examples of the reducing agent used here include, but are not limited to, NaBH(OAc)3, 2-picoline borane, NaBH3CN, etc. The solvent used here is also not limited to, but includes halogenated hydrocarbons such as dichloromethane, dichloroethane, and chloroform; ether solvents such as tetrahydrofuran, diethyl ether, and 1,4-dioxane; alcoholic solvents such as methanol and ethanol; and acetonitrile. (Fourth step) In this step, compound (4)-1 is obtained by subjecting (4)-1' to deprotection conditions. The reaction conditions are the same as those in Drug Production Method 1. (Drug Raw Material Manufacturing Method 11) This production method is for the production of compound (45)-1' contained in compound (45), which is a raw material of Drug Raw Material Production Method 10, and PG of compound (45)-1' contained in compound (45). E3The compound (45)-1 in which the moiety is H is prepared by the method of the present invention. (In the formula, LG Ｅ３ represents a leaving group. Examples of the leaving group include Cl, Br, a methanesulfonyloxy group, and a p-toluenesulfonyloxy group. (The same applies below.) (First step) In this step, compound (50) and compound (51) are subjected to alkylation reaction conditions to obtain compound (45)-1′. This reaction is carried out by using equal equivalents of compound (50) and compound (51), or an excess equivalent of either, in a reaction-inert solvent in the presence of a base, and stirring under ice-cooling to reflux for typically 1 hour to 1 day. Examples of the base used here include, but are not limited to, sodium hydride, tBuOK, LHMDS, NHMDS, potassium carbonate, and cesium carbonate. Examples of the solvent used here include, but are not limited to, ether solvents such as tetrahydrofuran, diethyl ether, and 1,4-dioxane, as well as DMF and MeCN. Here, when the compound obtained by the above reaction has a protecting group, the compound obtained can be subjected to deprotection reaction conditions following the reaction to obtain compound (45)-1′. The reaction conditions are the same as those in Drug Production Method 1. (Second process) In this step, compound (45)-1' is subjected to deprotection conditions to obtain compound (45)-1. The reaction conditions are the same as those in Drug Production Method 1. (Drug Raw Material Manufacturing Method 12) This production method is for the production of compound (45)-2' contained in compound (45), which is a raw material of Drug Raw Material Production Method 10, and PG of compound (45)-2' contained in compound (45). E3 The compound (45)-2, wherein the moiety is H, is prepared by the method of the present invention. (First step) In this step, compound (52) and compound (53) are subjected to coupling reaction conditions using a copper catalyst to obtain compound (45)-2'. This reaction is carried out by using equimolar amounts of compound (52) and compound (53), or an excess of one, in a reaction-inert solvent, a copper catalyst, a ligand, and a base, and stirring at room temperature or under reflux for typically 1 hour to 5 days. Examples of copper catalysts used herein include, but are not limited to, copper(I) iodide, copper(I) chloride, and copper(I) oxide. Examples of ligands used herein include, but are not limited to, DMEDA and trans-N,N'-dimethylcyclohexane-1,2'-diamine. Examples of bases used herein include, but are not limited to, organic bases such as diisopropylethylamine and triethylamine, and inorganic bases such as potassium carbonate, cesium carbonate, sodium carbonate, and tripotassium phosphate. Examples of solvents used herein include, but are not limited to, ether solvents such as tetrahydrofuran and 1,4-dioxane, alcohol solvents such as methanol and ethanol, dimethyl sulfoxide, N,N-dimethylformamide, water, and the like. In addition, it may be advantageous to heat the mixture by microwave irradiation in order to ensure smooth progress of the reaction. (Second process) In this step, compound (45)-2' is subjected to deprotection conditions to obtain compound (45)-2. The reaction conditions are the same as those in Drug Production Method 1. (Drug Raw Material Manufacturing Method 13) This production method is a method for producing compound (4)-2, which is included in compound (4), which is an intermediate in Drug Raw Material Production Method 1. (wherein PG of compound (51) E3 For compounds in which the moiety is H, the same reaction is carried out to obtain compound (4)-2' PG E3 It is possible to prepare a compound in which the moiety is H. (The same applies below.) (First step) In this step, compound (54) and compound (50) are subjected to Suzuki-Miyaura coupling reaction conditions to obtain compound (55). The reaction conditions are the same as those in the fourth step of Drug Substance Preparation Method 2. (Second process) In this step, compound (55) and compound (51) are subjected to alkylation reaction conditions to obtain compound (4)-2'. The reaction conditions are the same as those in the first step of Drug Substance Production Method 11. (Third step) In this step, compound (4)-2' is subjected to deprotection conditions to obtain compound (4)-2. The reaction conditions are the same as those in Drug Production Method 1. (Drug Raw Material Manufacturing Method 14) This production method is a method for producing compound (4)-3, which is included in compound (4), which is an intermediate in Drug Raw Material Production Method 1. (In the formula, LG Z represents a leaving group. Examples of the leaving group include Cl, Br, methanesulfonyloxy group, p-toluenesulfonyloxy group, etc. (The same applies below.) (First step) In this step, compound (54) and compound (56) are subjected to Suzuki-Miyaura coupling reaction conditions to obtain compound (57). The reaction conditions are the same as those in the fourth step of Drug Substance Preparation Method 2. (Second process) In this step, compound (57) and compound (53) are subjected to coupling reaction conditions using a copper catalyst to obtain compound (4)-3'. The reaction conditions are the same as those in the first step of Drug Substance Production Method 12. (Third step) In this step, compound (4)-3' is subjected to deprotection conditions to obtain compound (4)-3. The reaction conditions are the same as those in Drug Production Method 1. (Drug Raw Material Manufacturing Method 15) This production method is a method for producing compound (4)-1, which is included in compound (4), which is an intermediate in Drug Raw Material Production Method 1. (wherein PG of compound (45) E3 Compound (4)-1 can be produced by the same reaction as for a compound in which the moiety is H. (The same applies below.) (First step) In this step, compound (54) and compound (45) are subjected to Suzuki-Miyaura coupling reaction conditions to obtain compound (4)-1'. The reaction conditions are the same as those in the fourth step of Drug Substance Preparation Method 2. (Second process) In this step, compound (4)-1' is subjected to deprotection conditions to obtain compound (4)-1. The reaction conditions are the same as those in Drug Production Method 1. (Drug Raw Material Manufacturing Method 16) This production method is a method for producing compound (4)-5, which is included in compound (4), which is an intermediate in Drug Raw Material Production Method 1. (In the formula, LG Ｚ3 represents a leaving group. Examples of the leaving group include Cl, Br, a methanesulfonyloxy group, and a p-toluenesulfonyloxy group. (The same applies below.) (First step) In this step, compound (58) and compound (59) are subjected to cyclization reaction conditions to obtain compound (60). This reaction is carried out by using equal equivalents of compound (58) and compound (59), or an excess equivalent of either, in a reaction-inert solvent in the presence of a base, stirring under ice-cooling to reflux, typically for 1 hour to 5 days. Examples of the base used here include, but are not limited to, organic bases such as triethylamine and N,N'-diisopropylethylamine, and inorganic bases such as potassium carbonate and cesium carbonate. Examples of the solvent used here include, but are not limited to, ether solvents such as tetrahydrofuran and 1,4-dioxane, and N,N-dimethylformamide. (Second process) In this step, compound (60) and compound (54) are subjected to Suzuki-Miyaura coupling reaction conditions to obtain compound (61). The reaction conditions are the same as those in the fourth step of Drug Substance Preparation Method 2. (Third step) In this step, compound (61) is subjected to cyclization reaction conditions to obtain compound (4)-5'. The reaction conditions were the same as those in the third step of Drug Substance Production Method 17. (Fourth step) In this step, compound (4)-5' is subjected to deprotection conditions to obtain compound (4)-5. The reaction conditions are the same as those in Drug Production Method 1. (Drug Raw Material Manufacturing Method 17) This production method is a method for producing compound (4)-6. Compound (4)-6 can be used in place of compound (4) described in Drug Substance Production Method 1 to synthesize some of the compounds included in the compound of formula (1). (In the formula, L 17 But -(-L 2 -L 3 -L 4 )- and L 2 But C 1-3 Piperidinediyl optionally substituted with alkyl, C 1-3 Piperazinediyl optionally substituted with alkyl, C 1-3 pyrrolidinediyl, 3,8-diazabicyclo[3.2.1]octanediyl, or 2,6-diazaspiro[3.4]octanediyl, which may be substituted by alkyl; L 3 is the bond, -N(R L3 )-, C 1-3 alkylene or piperazinediyl, and L 4 is the bond, -N(R L4 )-, -O-, piperazinediyl or C 1-3 alkylene, and R L3 But H or C 1-3 alkyl, and R L4 But H or C 1-3 alkyl, PG L represents a protecting group for NH or OH. LG is C 1-12 (This indicates an alkyl group. The same applies below.) (First step) In this step, compound (62) and compound (63) are subjected to Michael addition reaction conditions to obtain compound (64). This reaction is carried out by using equivalent amounts of compound (62) and compound (63), or an excess equivalent of either, in the presence of a base and an excess amount of an acid reagent, stirring at room temperature or under reflux for typically 1 to 5 days. Examples of the base used here include, but are not limited to, organic bases such as 1,8-diazabicyclo[5.4.0]undec-7-ene and N,N'-diisopropylethylamine. Examples of the acid reagent used here include, but are not limited to, lactic acid, trifluoroacetic acid, acetic acid, etc. (Second process) In this step, compound (64) is subjected to urea-forming reaction conditions to obtain compound (65). This reaction is carried out by stirring compound (64), a urea-forming reagent, and an acid in a reaction-inert solvent or without a solvent at room temperature or under reflux, typically for 1 to 5 days. Examples of the urea-forming reagent used here include, but are not limited to, sodium cyanate or potassium cyanate. Examples of the acid used here include, but are not limited to, acetic acid, hydrochloric acid, trifluoroacetic acid, and the like. Examples of the solvent used here include, but are not limited to, halogenated hydrocarbons such as dichloromethane, dichloroethane, and chloroform; ether solvents such as tetrahydrofuran and 1,4-dioxane; acetic acid; toluene; water; and mixtures thereof. (Third step) In this step, compound (65) is subjected to cyclization reaction conditions to obtain compound (4)-6'. This reaction is carried out by stirring compound (65) in a reaction-inert solvent in the presence of a base under ice-cooling to reflux, usually for 1 hour to 5 days. Examples of the base used here include, but are not limited to, Triton B, potassium trimethylsilanolate, sodium ethoxide, etc. Examples of the solvent used here include, but are not limited to, ether solvents such as tetrahydrofuran and 1,4-dioxane, N,N-dimethylformamide, acetonitrile, etc. (Fourth step) In this step, compound (4)-6' is subjected to deprotection conditions to obtain compound (4)-6. The reaction conditions are the same as those in Drug Production Method 1. (Drug Raw Material Manufacturing Method 18) This production method is a method for producing compound (67). Compound (67) can be used in place of compound (4) described in Drug Substance Production Method 1 to synthesize some of the compounds included in the compound of formula (1). (In the formula, L １ But C 1-3 Piperidinediyl optionally substituted with alkyl, C 1-3 Piperazinediyl optionally substituted with alkyl, C 1-3 pyrrolidinediyl, 3,8-diazabicyclo[3.2.1]octanediyl, or 2,6-diazaspiro[3.4]octanediyl, which may be substituted by alkyl; L ２ is the bond, -N(R L3 )-, C 1-3 alkylene or piperazinediyl, and L ３ is the bond, -N(R L4 )-, -O-, piperazinediyl or C 1-3 alkylene, and R L3 But H or C 1-3 alkyl, and R L4 But H or C 1-3 is alkyl, and X L represents an oxygen atom or a nitrogen atom, and PG L1 represents a protecting group for NH or OH, and PG E3 indicates a protecting group for NH or H. The same applies below.) (First step) In this step, compound (66) and compound (65) are subjected to Ipso reaction conditions to obtain compound (67'). The reaction conditions are the same as those in the first step of Drug Substance Preparation Method 2. Alternatively, compound (67') can be prepared by subjecting the compound to coupling reaction conditions using a copper catalyst. The reaction conditions are the same as those in the first step of Drug Substance Production Method 12. Alternatively, compound (67') can be prepared by subjecting the compound to carbon-nitrogen bond forming reaction conditions. In this reaction, compound (66) and compound (65) are used in equivalent amounts or in an excess equivalent amount of either compound, and a metal catalyst, a ligand, and a base are added to a mixture thereof. The mixture is stirred in a reaction-inert solvent at 80°C or under reflux, usually for 1 hour to 5 days. Examples of metal reagent catalysts used herein include, but are not limited to, palladium(II) acetate, tris(dibenzylideneacetone)dipalladium, [1,1'-bis(diphenylphosphino)ferrocene]palladium(II) dichloride, and [1,1'-bis(diphenylphosphino)ferrocene]palladium(II) dichloride dichloromethane adduct. Examples of ligands include, but are not limited to, Xantphos, Ruphos, Xphos, BINAP, and the like. Examples of bases include, but are not limited to, inorganic bases such as potassium carbonate, sodium carbonate, cesium carbonate, and sodium tert-butoxide, and organic bases such as triethylamine and N,N-diisopropylethylamine. Examples of solvents include, but are not limited to, 1,4-dioxane, toluene, N,N-dimethylformamide, and mixtures thereof. This reaction may also be performed under microwave irradiation. Alternatively, compound (67') can be prepared by subjecting the compound to alkylation reaction conditions. The reaction conditions are the same as those in the first step of Raw Material Production Method 2. (Second process) In this step, compound (67) is obtained by subjecting compound (67') to deprotection conditions. The reaction conditions are the same as those in Drug Production Method 1. (Drug Raw Material Manufacturing Method 19) This production method is a method for producing compound (1)-2, which is included in compound (1), which is the raw material of the first production method of the drug. (L in the formula 1A and L 4Ais an optionally substituted heterocycloalkylene, an optionally substituted heteroarylene, a saturated 7- to 9-membered spiroheterocycloalkylene containing 1 to 2 nitrogen atoms, a saturated 7- to 9-membered bridged heterocycloalkylene containing 2 nitrogen atoms, and an optionally substituted C 1-６ alkylene; L 3A is C 1-3 Piperidinediyl optionally substituted with alkyl, C 1-3 Piperazinediyl optionally substituted with alkyl, C 1-3 It refers to pyrrolidinediyl, bridged piperazinediyl, or 2,6-diazaspiro[3.4]octanediyl, which may be substituted with alkyl. The same applies below. (First step) This step is a method for producing compound (69) by alkylation reaction of compound (14) with compound (68). The reaction conditions are the same as those in the seventh step of Drug Substance Preparation Method 2. (Second process) In this step, compound (69) is subjected to hydrolysis conditions to obtain compound (70). The reaction conditions are the same as those in the first step of Drug Substance Production Method 1. (Third step) This step is a step of subjecting compound (70) and compound (71) to condensation reaction conditions to obtain compound (1)-2. The reaction conditions are the same as those in the second step of Drug Substance Preparation Method 1. (Drug Raw Material Manufacturing Method 20) This production method is a method for producing compound (74). Compound (74) can be used in place of compound (4) described in Drug Substance Production Method 1 to synthesize some of the compounds included in the compound of formula (1). (wherein PG of compound (51) E3 Compound (74) can be produced by a similar reaction for a compound in which the moiety is H. (First step) This step is a step of subjecting compound (72) and compound (51) to nucleophilic substitution reaction conditions to obtain compound (73). The reaction conditions are the same as those in the first step of Drug Substance Production Method 11. (Second process) In this step, compound (73) is subjected to deprotection conditions to obtain compound (74). The reaction conditions are the same as those in Drug Production Method 1. (Drug Raw Material Manufacturing Method 21) This production method is a method for producing compound (2)-3, which is included in (2), the raw material of Drug Raw Material Production Method 1. (First step) This step is a method for producing compound (77) by reacting compound (75) with compound (76). This reaction is carried out by converting compound (75) to the corresponding enolate under acidic conditions using an orthoester such as trimethyl orthoformate, adding an equivalent amount of compound (76) or an excess amount of either compound, and stirring the mixture in a reaction-inert solvent under reflux, preferably at 60° C. to reflux, for usually 0.1 hours to 5 days. Examples of the solvent used here include, but are not limited to, aromatic hydrocarbons such as toluene, ethers such as THF and DOX, DMF, DMAc, etc. (Second process) This step is a method for producing compound (78) from compound (77). This reaction is carried out by stirring compound (77) in a reaction-inert solvent under reflux, preferably at 150° C. or higher, for a period of usually 0.1 hour to 5 days. Examples of the solvent used here include, but are not limited to, NMP. (Third step) This step is a method for producing compound (79) from compound (78). This reaction is carried out by stirring a mixture of compound (78) and a brominating agent in equal amounts, or in excess of one of the two, in a reaction-inert solvent or without a solvent, under cooling to reflux, preferably at room temperature, for typically 0.1 hours to 5 days. Examples of solvents used here include, but are not limited to, aromatic hydrocarbons such as toluene, ethers such as THF and DOX, halogenated hydrocarbons such as dichloromethane, and DMF. Examples of brominating agents include N-bromosuccinimide, N-bromosaccharin, 1,3-dibromo-5,5-dimethylhydantoin, and dibromoisocyanuric acid. (Fourth step) This step is a method for producing compound (80) from compound (79). The reaction conditions are the same as those for the first step of Drug Substance Production Method 8. (Fifth step) This step is a method for producing compound (81) by ipso substitution reaction between compound (80) and compound (6)-1. The reaction conditions are the same as those in the first step of Drug Substance Preparation Method 2. (Sixth step) This step is a method for producing compound (82) by ipso substitution reaction between compound (81) and compound (8)-1. The reaction conditions are the same as those in the first step of Drug Substance Preparation Method 2. (Seventh step) In this step, compound (82) and PG 3 This is a method for producing compound (82) by ipso substitution reaction with —OH. The PG used here 3 Examples of -OH include benzyl alcohol, p-methoxybenzyl alcohol, and 1-phenylethanol. The reaction conditions are the same as those in the first step of Drug Substance Preparation Method 2. (Eighth process) This step is a method for producing compound (84) by Suzuki-Miyaura coupling reaction between compound (83) and compound (12), which is a boronic acid derivative. The reaction conditions are the same as those in the fourth step of Drug Substance Preparation Method 2. When compound (84) has axial chirality, it is obtained as a mixture of stereoisomers, but each stereoisomer can be isolated by a conventional resolution procedure, for example, resolution using ODS column chromatography or silica gel column chromatography. In addition, the protecting group PG 2 After the deprotection reaction, compound (84) was deprotected under conditions different from those of PG 1 may be converted to another protecting group. The reaction conditions for the deprotection reaction used here are the same as those described in Drug Substance Production Method 1. PG to be subsequently converted 1 Examples of the protecting group include a tetrahydro-2H-pyran-2-yl group. As references for this reaction, for example, the following can be referred to. PGM Wuts and TW Greene, "Greene's Protective Groups in Organic Synthesis," 5th ed., John Wiley & Sons Inc., 2014 (Ninth step) This step is a method for producing compound (85) by deprotecting compound (84) through catalytic hydrogenation. The reaction conditions are the same as those in the sixth step of Drug Substance Preparation Method 2. (10th step) This step is a method for producing compound (2)-3 by reacting compound (85) with compound (15). The reaction conditions are the same as those in the seventh step of Drug Substance Preparation Method 2. (Drug Raw Material Manufacturing Method 22) This production method is a method for producing compound (4)-7, which is included in compound (4), which is an intermediate in drug raw material production method 1. (First step) This step is a method for producing compound (87) from compound (86). The reaction conditions were the same as those in the first step of Drug Substance Production Method 17. (Second process) This step is a method for producing compound (88) from compound (87). This reaction is carried out by adding an ammonia reagent to compound (87), triphosgene, and a base in a reaction-inert solvent at room temperature, usually for one to five days, followed by stirring. Examples of the ammonia reagent used here include, but are not limited to, ammonia methanol solution. Examples of the base used here include, but are not limited to, organic bases such as pyridine, triethylamine, and N,N-diisopropylethylamine. Examples of the solvent used here include, but are not limited to, halogenated hydrocarbons such as dichloromethane, dichloroethane, and chloroform. (Third step) This step is a method for producing compound (89) from compound (88). The reaction conditions were the same as those in the third step of Drug Substance Production Method 17. (Fourth step) In this step, compound (89) and compound (54) are subjected to Suzuki-Miyaura coupling reaction conditions to obtain compound (90). The reaction conditions are the same as those in the fourth step of Drug Substance Preparation Method 2. (Fifth step) In this step, compound (90) is subjected to deprotection conditions to obtain compound (4)-7. The reaction conditions are the same as those in Drug Production Method 1. (Drug Raw Material Manufacturing Method 23) This production method is a method for producing compound (45)-3, which is included in compound (45), which is the raw material for Drug Raw Material Production Method 10. In this step, compound (92) and compound (53) are subjected to coupling reaction conditions using a copper catalyst to obtain compound (45)-3. The reaction conditions are the same as those in the first step of Drug Substance Production Method 12. (Drug Raw Material Manufacturing Method 24) This production method is the first method for producing compound (1)-3 contained in starting compound (1). (First step) This step is a method for producing compound (1)-3 by cycloaddition reaction of compound (93) and compound (94). This reaction uses equal amounts of compound (93) and compound (94), or an excess of either. A mixture of these is stirred, preferably in the presence of a copper salt, more preferably in the presence of a copper salt and a reducing agent, in a reaction-inert solvent or without a solvent, under cooling to reflux, preferably at 0°C to 100°C, typically for 0.1 hours to 5 days. Examples of solvents used herein include, but are not limited to, halogenated hydrocarbons such as dichloromethane, 1,2-dichloroethane, and chloroform; aromatic hydrocarbons such as benzene, toluene, and xylene; ethers such as diethyl ether, THF, DOX, and 1,2-dimethoxyethane; DMF, DMSO, ethyl acetate, MeCN, tBuOH, water, and mixtures thereof. Examples of copper salts include CuI, CuSO, and copper(I) trifluoromethanesulfonate (CuOTf). Examples of reducing agents include sodium ascorbate. In some cases, it may be advantageous to carry out the reaction in the presence of TEA, DIPEA, N-methylmorpholine (NMM), 2,6-lutidine, tris[(1-benzyl-1H-1,2,3-triazol-4-yl)methyl]amine (TBTA), etc., in order to ensure smooth reaction. [Literature] Angew. Chem. Int. Ed. 2002, 41, p.2596-2599. In addition, PG of compound (93) 1 Alternatively, the compound obtained by first subjecting the compound to a deprotection reaction may be used to carry out this reaction. (Drug Raw Material Manufacturing Method 25) (where R is C 1-3 (This indicates an alkyl group. The same applies below.) This production method is the second method for producing compound (1)-3 contained in starting compound (1). (First step) This step is a method for producing compound (96) by cycloaddition reaction of compound (93) with compound (95). The reaction conditions were the same as those in the first step of Drug Substance Production Method 24. (Second process) This step is a method for producing compound (97) by hydrolyzing compound (96). This reaction is carried out by stirring compound (96) under cooling or reflux, usually for 0.1 hours to 5 days. Examples of solvents used here include, but are not limited to, alcohols, acetone, DMF, THF, etc. Mixing the above solvents with water may also be suitable for the reaction. Examples of hydrolysis reagents include, but are not limited to, aqueous sodium hydroxide, aqueous potassium hydroxide, trimethyltin hydroxide, etc. As references for this reaction, for example, the following can be referred to. "Experimental Chemistry Lectures (5th Edition)" edited by the Chemical Society of Japan, Vol. 16 (2005) (Maruzen) Angew. Chem. Int. Ed. 2005, 44, p.1378-1382. (Third step) This step is a method for producing compound (1)-3 by an amidation reaction between compound (97) and compound (98). In this reaction, a mixture of compound (97) and compound (98) is used in equal amounts or in excess of one, and is stirred in the presence of a condensing agent in a reaction-inert solvent under cooling to heating, preferably at −20° C. to 60° C., usually for 0.1 hours to 5 days. Examples of the solvent include, but are not limited to, aromatic hydrocarbons such as toluene, ethers such as THF and DOX, halogenated hydrocarbons such as dichloromethane, alcohols, DMF, DMSO, ethyl acetate, MeCN, and mixtures thereof. Examples of condensing agents include (benzotriazol-1-yloxy)tripyrrolidinophosphonium hexafluorophosphate (PyBOP), O-(7-azabenzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate (HATU), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide or its hydrochloride, N,N'-dicyclohexylcarbodiimide (DCC), 1,1'-carbonyldiimidazole (CDI), and diphenylphosphoric acid azide (DPPA). The use of an additive (e.g., 1-hydroxybenzotriazole) may be preferable for the reaction. Conducting the reaction in the presence of an organic base such as TEA, DIPEA, or NMM, or an inorganic base such as potassium carbonate, sodium carbonate, or potassium hydroxide may be advantageous for smooth reaction progression. Alternatively, compound (97) can be converted into a reactive derivative and then acylated. Examples of reactive derivatives of carboxylic acids include acid halides obtained by reaction with a halogenating agent such as phosphorus oxychloride or thionyl chloride, mixed acid anhydrides obtained by reaction with isobutyl chloroformate, and activated esters obtained by condensation with 1-hydroxybenzotriazole. The reaction of these reactive derivatives with compound (98) can be carried out in a reaction-inert solvent such as halogenated hydrocarbons, aromatic hydrocarbons, or ethers, under cooling to heating, preferably at -20°C to 120°C. [Literature] S.R. Sandler and W. Karo, Organic Functional Group Preparations, 2nd ed., Vol. 1, Academic Press Inc., 1991 "Experimental Chemistry Lectures (5th Edition)" edited by the Chemical Society of Japan, Vol. 16 (2005) (Maruzen) (Drug Raw Material Manufacturing Method 26) This is the first method for producing the starting compound (93). This production method is a method for producing compound (93) by reacting compound (14) with compound (100). This reaction is carried out by reacting a mixture of compound (14) and compound (100) in the presence of a base in a reaction-inert solvent under cooling to reflux, preferably at 0°C to 80°C, for typically 0.1 hours to 5 days. Examples of the solvent include, but are not limited to, aromatic hydrocarbons such as benzene, toluene, and xylene; alcohols such as MeOH and EtOH; ethers such as diethyl ether, THF, DOX, and 1,2-dimethoxyethane; halogenated hydrocarbons such as dichloromethane, 1,2-dichloroethane, and chloroform; DMF, DMSO, ethyl acetate, MeCN, and mixtures thereof. Examples of the base include, but are not limited to, organic bases such as TEA, DIPEA, 1,8-diazabicyclo[5.4.0]-7-undecene, n-butyllithium, and tBuOK; and inorganic bases such as sodium hydroxide, sodium carbonate, potassium carbonate, cesium carbonate, and sodium hydride. It may be advantageous to carry out the reaction in the presence of a phase transfer catalyst such as tetra-n-butylammonium chloride. As references for this reaction, for example, the following can be referred to. Chemical Society of Japan, "Experimental Chemistry Lectures," 5th edition, Vol. 14, Maruzen, 2005 Compound (93) may have axial chirality and may be obtained as a mixture of stereoisomers. 2Compound (93), in which is a protecting group, or a compound obtained by subjecting compound (93) to a deprotection reaction, can be subjected to a conventional resolution procedure, for example, resolution using ODS column chromatography or silica gel column chromatography, to isolate each stereoisomer. The reaction conditions for the deprotection reaction used here are the same as those described in the first drug production process. Compound (100) is also LG 1 By halogenating a compound in which the moiety corresponding to LG is a hydroxy group, 1 is a halogen. Examples of the halogenating agent used here include, but are not limited to, thionyl chloride, phosphorus oxychloride, hydrobromic acid, phosphorus tribromide, etc. As references for this reaction, for example, the following can be referred to. Chemical Society of Japan, "Experimental Chemistry Lectures," 5th edition, Vol. 13, Maruzen, 2004 Furthermore, compound (100) is LG 1 The compound having a hydroxy group in the corresponding position is sulfonylated in the presence of a base to give LG 1 is a sulfonyloxy group. Examples of the sulfonylation reagent used here include, but are not limited to, methanesulfonyl chloride, p-toluenesulfonyl chloride, methanesulfonic anhydride, etc. Examples of the base include, but are not limited to, TEA, DIPEA, pyridine, tetramethylethylenediamine, etc. As references for this reaction, for example, the following can be referred to. Synthesis 1999, 9, p.1633-1636 (Drug Raw Material Manufacturing Method 27) This is the second method for producing the starting compound (93). (First step) This step is a method for producing compound (101) by reacting compound (21) with compound (100). The reaction conditions were the same as in Drug Substance Production Method 26. (Second process) This step is a method for producing compound (93) by ipso substitution reaction between compound (101) and compound (8). The reaction conditions are the same as those in the first step of Drug Substance Preparation Method 2. Compound (93) may have axial chirality and may be obtained as a mixture of stereoisomers. 2 Compound (93), in which is a protecting group, or a compound obtained by subjecting compound (93) to a deprotection reaction, can be subjected to a conventional resolution procedure, for example, resolution using ODS column chromatography or silica gel column chromatography, to isolate each stereoisomer. The reaction conditions for the deprotection reaction used here are the same as those described in the first drug production process. (Drug Raw Material Manufacturing Method 28) (PG in the formula 4 , P.G. 5 indicates a protecting group.) This production method is a method for producing the starting compound (94). (First step) This step is a method for producing compound (103) by an amidation reaction between compound (98) and compound (102). The reaction conditions were the same as those in the third step of Drug Substance Preparation Method 25. (Second process) This step is a method for producing compound (104) by subjecting compound (103) to a deprotection reaction. The reaction conditions are the same as those described in the first drug production process. (Third step) This step is a method for producing compound (31) by amidation reaction of compound (104) with compound (105). The reaction conditions were the same as those in the third step of Drug Substance Preparation Method 25. (Fourth step) This step is a method for producing compound (107) by subjecting compound (106) to a deprotection reaction. The reaction conditions are the same as those described in the first drug production process. (Fifth step) This step is a method for producing compound (94) by reacting compound (107) with a diazo transfer reagent. In this reaction, compound (107) is treated with an equivalent or excess amount of a diazotransfer reagent in a reaction-inert solvent under cooling to heating, preferably at 0°C to 50°C, typically for 0.1 hours to 3 days. Examples of diazotransfer reagents include, but are not limited to, trifluoromethanesulfonyl azide, imidazole-1-sulfonyl azide or its salts, and 2-azido-1,3-dimethylimidazolinium hexafluorophosphate (ADMP). It may be advantageous to carry out the reaction in the presence of an organic base such as TEA, 4-dimethylaminopyridine (DMAP), or 2,6-lutidine, or a catalytic amount of a copper salt such as CuSO. Examples of solvents include halogenated hydrocarbons such as THF and dichloromethane, MeCN, alcohols, water, and mixtures thereof. [Literature] J. Org. Chem. 2012, 77, p.1760-1764 Nature 2019, 574, pp.86-89 Org. Biomol. Chem. 2014, 12, p.4397-4406 (Drug Raw Material Manufacturing Method 29) (PG in the formula 11 represents a tert-butyl group, and R 3A is -O- or -N(R P )- indicates. This production method is a method for producing the starting compound (120). (First step) This step is a method for producing compound (108) by hydrolyzing compound (5)-1. This reaction is carried out by stirring compound (5)-1 under cooling or reflux, usually for 0.1 hours to 5 days. Examples of the solvent used here include, but are not limited to, alcohols, acetone, DMF, THF, etc. Furthermore, a mixed solvent of the above solvent with water may be suitable for the reaction. Examples of the hydrolysis reagent include, but are not limited to, aqueous sodium hydroxide, aqueous potassium hydroxide, etc. As references for this reaction, for example, the following can be referred to. "Experimental Chemistry Lectures (5th Edition)" edited by the Chemical Society of Japan, Vol. 16 (2005) (Maruzen) Angew. Chem. Int. Ed. 2005, 44, p.1378-1382. (Second process) In this step, the hydroxyl group of compound (108) is converted to a tert-butyl group (PG 11 ) to prepare compound (109). This reaction is carried out by stirring compound (108) under cooling or reflux, usually for 0.1 hours to 5 days. Examples of solvents used here include, but are not limited to, ethers such as THF and DOX, halogenated hydrocarbons such as dichloromethane, tBuOH, DMF, etc. Examples of tert-butyl protecting reagents include, but are not limited to, isobutene and 2-tert-butyl-1,3-diisopropylisourea. Alternatively, compound (109) can be produced by a dehydration condensation reaction between compound (108) and tBuOH. As references for this reaction, for example, the following can be referred to. PGM Wuts and TW Greene, "Greene's Protective Groups in Organic Synthesis," 5th ed., John Wiley & Sons Inc., 2014 Org. Lett., 2012, 14, 17, p.4678-4681 (Third step) In this step, compound (109) and RLG This is a method for producing compound (110) by an ipso substitution reaction with —SH. The reaction conditions are the same as those in the first step of Drug Substance Preparation Method 2. (Fourth step) This step involves the reaction of compound (110) with PG 3 This is a method for producing compound (111) by an ipso substitution reaction with —OH. The reaction conditions are the same as those in the first step of Drug Substance Preparation Method 2. (Fifth step) In this step, compound (111) and R Q This is a method for producing compound (112) by Suzuki-Miyaura coupling reaction with a boronic acid derivative comprising a -boronic acid group or the like. The reaction conditions are the same as those in the fourth step of Drug Substance Preparation Method 2. Compound (111) is dehalogenated using a Pd catalyst and a reducing agent to give compound (112) (where R Q can produce hydrogen). [Literature] J. Org. Chem., 1977, 42, p.3491-3494 Tetrahedron Letters 2013, 54, 5207-5210 (Sixth step) This step is a method for producing compound (113) by Suzuki-Miyaura coupling reaction between compound (112) and compound (12). The reaction conditions are the same as those in the fourth step of Drug Substance Preparation Method 2. (Seventh step) This step is a method for producing compound (114) by oxidation reaction of compound (113). The reaction conditions are the same as those in the fifth step of Drug Substance Preparation Method 3. When compound (114) has axial chirality, it may be obtained as a mixture of stereoisomers. However, each stereoisomer can be isolated by a conventional resolution procedure, for example, resolution using ODS column chromatography or silica gel column chromatography. In addition, the protecting group PG 1After the deprotection reaction, compound (114) was deprotected under conditions different from those of PG 2 may be converted to another protecting group. The reaction conditions for the deprotection reaction used here are the same as those described in the first drug production process. PG to be subsequently converted 2 Examples of the protecting group include a tetrahydro-2H-pyran-2-yl group. As references for this reaction, for example, the following can be referred to. PGM Wuts and TW Greene, "Greene's Protective Groups in Organic Synthesis," 5th ed., John Wiley & Sons Inc., 2014 (Eighth process) This step is a method for producing compound (115) by deprotecting compound (114) through catalytic hydrogenation. The reaction conditions are the same as those in the sixth step of Drug Substance Preparation Method 2. (Ninth step) This step is a method for producing compound (116) by reacting compound (115) with compound (100). The reaction conditions were the same as those in the first step of Drug Substance Production Method 26. (10th step) This step is a method for producing compound (117) by an ipso substitution reaction between compound (116) and compound (8). The reaction conditions are the same as those in the first step of Drug Substance Preparation Method 2. (Eleventh step) This step is a method for producing compound (118) by subjecting compound (117) to a deprotection reaction. The reaction conditions are the same as those described in the first drug production process. (Twelfth step) This step is a method for producing compound (120) by reacting compound (118) with compound (119). This reaction involves using equal amounts of compound (118) and compound (119) or an excess of either compound. A mixture of these compounds is stirred in the presence of a condensing agent in a reaction-inert solvent under cooling to heating, preferably at temperatures between -20°C and 60°C, typically for 0.1 hours to 5 days. Examples of solvents include, but are not limited to, aromatic hydrocarbons such as toluene, ethers such as THF and DOX, halogenated hydrocarbons such as dichloromethane, alcohols, DMF, DMSO, ethyl acetate, MeCN, and mixtures thereof. Examples of condensing agents include PyBOP, HATU, and CDI. Carrying out the reaction in the presence of an organic base such as TEA, DIPEA, or NMM, or an inorganic base such as potassium carbonate, sodium carbonate, or cesium carbonate, may be advantageous for smooth reaction progression. II. Drug-Linker Conjugates (L A -D) manufacturing method (Drug-Linker Conjugate Production Method 1) Among the drug-linker conjugates used in the synthesis of the antibody-drug conjugate of the present invention, the drug-linker conjugate represented by formula (LD-27) can be obtained by reacting compound (121) with compound (122) in the presence of a base, and then reacting the resulting compound with a drug. (In the formula, R st1 is C 1-12 alkylene, and R AA are each independently H, methyl, isopropyl, benzyl, -(CH2)4-NH2, -(CH2)3-NH-C(=NH)-NH2, or -(CH2)3-NH-C(=O)-NH2, and d is an integer from 2 to 4. Furthermore, DH represents a drug, and the H in said DH represents a hydrogen atom of -NH- or -OH contained in said drug. The same applies below.) As references for this reaction, for example, the following can be referred to. International Publication No. 2004 / 010957 (Drug-Linker Conjugate Production Method 2) Among the drug-linker conjugates used in the synthesis of the antibody-drug conjugate of the present invention, the drug-linker conjugate represented by formula (LD-28) can be obtained by reacting a drug with compound (123) in the presence of a condensing agent. (In the formula, R st1 is C 1-12 alkylene, and R AA are each independently H, methyl, isopropyl, benzyl, -(CH2)4-NH2, -(CH2)3-NH-C(=NH)-NH2, or -(CH2)3-NH-C(=O)-NH2, and d is an integer from 2 to 4. As references for this reaction, for example, the following can be referred to. International Publication No. 2023 / 037268 III. Synthesis of Antibody-Drug Conjugates Among the antibody-drug conjugates of the present invention, the antibody-drug conjugate represented by formula (AD-26) can be obtained by reacting an antibody or antigen-binding fragment (Ab) with a drug-linker conjugate (LD-29). (In the formula, R st1 is C 1-12 alkylene, and R AA are each independently H, methyl, isopropyl, benzyl, -(CH)-NH, -(CH)-NH-C(=NH)-NH, or -(CH)-NH-C(=O)-NH, d is an integer from 2 to 4, t is 0 or 1, and n is a number from 2 to 8. As references for this reaction, for example, the following can be referred to. International Publication No. 2004 / 010957 The antibody-drug conjugate of formula (I) or a salt thereof is isolated and purified as a free compound, a salt thereof, a hydrate, a solvate, or a crystalline polymorph, or as an amorphous solid substance. The salt of the antibody-drug conjugate of formula (I) can also be produced by a conventional salt-forming reaction. Isolation and purification are carried out by applying conventional chemical procedures such as extraction, fractional crystallization, and various fractional chromatography. Various isomers can be produced by selecting appropriate starting compounds, or can be separated by taking advantage of the differences in physicochemical properties between isomers. For example, optical isomers can be obtained by a general optical resolution method for a racemate (e.g., fractional crystallization leading to diastereomeric salts with an optically active base or acid, or chromatography using a chiral column, etc.), or can also be produced from appropriate optically active starting compounds. Furthermore, the antibody-drug conjugate of formula (I) or a salt thereof, or an intermediate thereof may have axial asymmetry and be obtained as a mixture of stereoisomers. However, each stereoisomer can be isolated by a conventional resolution procedure, for example, resolution using octadecylsilyl (ODS) column chromatography or silica gel column chromatography. The pharmacological activity of the antibody-drug conjugate of formula (I) or a salt thereof can be confirmed by the methods described in the Test Examples. 6. Pharmaceutical Compositions The present invention also provides a pharmaceutical composition containing the antibody-drug conjugate of the present invention or a salt thereof (also referred to as the "pharmaceutical composition of the present invention"). The pharmaceutical composition of the present invention, which contains one or more of the antibody-drug conjugates of formula (I) or salts thereof as an active ingredient, can be prepared by a commonly used method using excipients commonly used in the art, i.e., pharmaceutical excipients, pharmaceutical carriers, etc. The dosage form of the pharmaceutical composition of the present invention may be, for example, an injection, a drip infusion, a suppository, eye drops, an eye ointment, a transdermal liquid, an ointment, a transdermal patch, a transmucosal liquid, a transmucosal patch, an inhalant, or the like, and may be administered parenterally, for example, intraarticularly, intravenously, intramuscularly, subcutaneously, intraperitoneally, or intratumorally. Injections and drip infusions can be administered by an appropriate method, for example, intravenously, subcutaneously, intraperitoneally, or intratumorally. Injectable preparations for parenteral administration contain sterile aqueous or non-aqueous solutions, suspensions, or emulsions. Aqueous solvents include, for example, distilled water for injection or physiological saline. Non-aqueous solvents include alcohols such as EtOH. Such compositions may further contain an isotonic agent, preservative, wetting agent, emulsifier, dispersant, stabilizer, or solubilizer. These are sterilized, for example, by filtration through a bacteria-retaining filter, addition of a sterilizer, or irradiation. Alternatively, sterile solid compositions can be prepared and dissolved or suspended in sterile water or a sterile injectable solvent before use. Although it varies depending on the route of administration, dosage form, administration site, and types of excipients and additives, the pharmaceutical composition of the present invention contains 0.01 to 100% by weight, and in one embodiment, 0.01 to 50% by weight, of one or more compounds of formula (I) or salts thereof as active ingredients. The antibody-drug conjugate of formula (I) or a salt thereof can be used in combination with various therapeutic or preventive agents for diseases for which the antibody-drug conjugate of formula (I) or a salt thereof is considered to be effective. The combination may be administered simultaneously, or separately, consecutively, or at a desired time interval. The simultaneous administration preparation may be a combined preparation or may be formulated separately. 7. Medical Uses of the Pharmaceutical Composition of the Present Invention The antibody-drug conjugate or a salt thereof of the present invention and the pharmaceutical composition of the present invention (hereinafter collectively referred to as the "pharmaceutical composition, etc. of the present invention") can be used for the treatment of cancer. The present invention also includes a method for treating cancer, which comprises administering a therapeutically effective amount of the pharmaceutical composition, etc. of the present invention to a subject. The present invention also includes the use of the antibody-drug conjugate or a salt thereof of the present invention in the manufacture of a pharmaceutical composition for the treatment of cancer. Cancers to be treated with the pharmaceutical composition etc. of the present invention may be either blood cancers or solid cancers, and the target of treatment is not particularly limited, but examples thereof include blood cancers such as gastric cancer, lung cancer, acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), Hodgkin's lymphoma, non-Hodgkin's lymphoma, B-cell lymphoma, multiple myeloma, and T-cell lymphoma, myelodysplastic syndrome, adenocarcinoma, squamous cell carcinoma, adenosquamous carcinoma, undifferentiated carcinoma, large cell carcinoma, non-small cell lung cancer, small cell lung cancer, mesothelioma, skin cancer, cutaneous T-cell lymphoma, breast cancer, prostate cancer, and bladder cancer. Examples of cancers include solid cancers such as vaginal cancer, cervical cancer, head and neck cancer, uterine cancer, cervical cancer, liver cancer, gallbladder cancer, bile duct cancer, kidney cancer, pancreatic cancer, colon cancer, large intestine cancer, rectal cancer, small intestine cancer, stomach cancer, esophageal cancer, testicular cancer, ovarian cancer, and brain tumors, as well as cancers of bone tissue, cartilage tissue, adipose tissue, muscle tissue, vascular tissue, and hematopoietic tissue, as well as sarcomas such as chondrosarcoma, Ewing's sarcoma, malignant hemangioendothelioma, malignant schwannoma, osteosarcoma, and soft tissue sarcoma, and blastomas such as glioblastoma, glioblastoma multiforme, hepatoblastoma, medulloblastoma, nephroblastoma, neuroblastoma, pancreatoblastoma, pleuropulmonary blastoma, and retinoblastoma. In one embodiment, the cancer to be treated with the pharmaceutical composition etc. of the present invention is a cancer expressing G12D mutant KRAS in cells. To provide a further understanding of the present invention, reference is now made to specific examples which are provided for purposes of illustration and not limitation. Hereinafter, based on the examples, the antibody-drug conjugate of formula (I) or a salt thereof, and the drug (D) and drug-linker conjugate (L) that constitute the antibody-drug conjugate or salt thereof will be described. A The antibody-drug conjugates or salts thereof described in the following Examples are specific antibody-drug conjugates or salts thereof included in formula (I), but the methods for producing the antibody-drug conjugates or salts thereof of formula (I) are not limited to the methods described in the following Examples, and the antibody-drug conjugates or salts thereof of formula (I) can also be produced by a combination of these production methods or by methods that would be obvious to one skilled in the art. In this specification, naming software such as ACD / Name (registered trademark, Advanced Chemistry Development, Inc.) may be used to name compounds. For convenience, the concentration in mol / L is expressed as M. For example, a 1M aqueous solution of sodium hydroxide means a 1 mol / L aqueous solution of sodium hydroxide. Example 1 Synthesis of Drug (D) Drugs D1 to D6 were synthesized according to the methods described in Examples 8, 20, 23, 48, 70 and 72 of WO 2022 / 173032. The synthesis methods for drugs D7 to D12 are shown below. The numbers assigned to each intermediate indicate the step in the synthetic pathway in which the intermediate was synthesized. For example, the intermediate synthesized in the first step of the synthesis of drug D7 is designated D7-1. Synthesis of drug D7 (First step) 7-Bromo-2,4-dichloro-8-fluoro-6-iodoquinazoline (40 g) was suspended in THF (400 mL). Under ice cooling, aqueous sodium hydroxide (1 M, 190 mL) was added dropwise to maintain the internal temperature below 10°C, and the mixture was stirred for 2 hours. The reaction mixture was poured into an Erlenmeyer flask containing hydrochloric acid (1 M, 190 mL) and ice water (approximately 900 g) and stirred at room temperature for approximately 30 minutes (until the ice melted). The insoluble matter was filtered, washed with water, and dried under reduced pressure to give 7-bromo-2-chloro-8-fluoro-6-iodoquinazolin-4-ol (D7-1, 33.56 g) as a solid. (Second process) To a mixture of 7-bromo-2-chloro-8-fluoro-6-iodoquinazolin-4-ol (D7-1, 24.6 g) and THF (260 mL) heated to 60 °C under a nitrogen stream, 2-tert-butyl-1,3-diisopropylisourea (73.4 g) was added dropwise over 15 minutes. The mixture was stirred at that temperature for 2.5 hours. The mixture was allowed to cool to room temperature, and the colorless solid was filtered off, washing with THF (approximately 500 mL). The filtrate was concentrated, and the resulting solid was added to MeOH (210 mL) and stirred at room temperature for 1 hour for suspension washing. The solid was collected by filtration using MeOH (100 mL) to give 7-bromo-4-tert-butoxy-2-chloro-8-fluoro-6-iodoquinazoline (D7-2, 23.2 g) as a solid. (Third step) Ethanethiol (3.6 mL) and DABCO (7.7 g) were added to a suspension of 7-bromo-4-tert-butoxy-2-chloro-8-fluoro-6-iodoquinazoline (D7-2, 21 g) in CHCl (200 mL) at room temperature, and the mixture was stirred overnight at room temperature under an argon atmosphere. Water was added to quench the reaction under ice cooling. CHCl was added, and the organic and aqueous layers were separated. The aqueous layer was extracted three times with CHCl. ​​The combined organic layers were dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to give 7-bromo-4-tert-butoxy-2-(ethylsulfanyl)-8-fluoro-6-iodoquinazoline (D7-3, 23.4 g) as a solid. (Fourth step) To a solution of 7-bromo-4-tert-butoxy-2-(ethylsulfanyl)-8-fluoro-6-iodoquinazoline (D7-3, 32 g) and (1S)-1-phenylethan-1-ol (11 mL) in THF (400 mL) was added tBuOK (10 g) under ice-cooling and stirred for 1 hour under argon atmosphere. The reaction was quenched by the addition of saturated aqueous ammonium chloride solution under ice-cooling. Water and ethyl acetate were added, and the organic and aqueous layers were separated. The organic layer was washed with saturated aqueous sodium chloride and dried over anhydrous sodium sulfate. After filtration and concentration under reduced pressure, the residue was purified by silica gel column chromatography (hexane / ethyl acetate) to give 7-bromo-4-tert-butoxy-2-(ethylsulfanyl)-6-iodo-8-[(1S)-1-phenylethoxy]quinazoline (D7-4, 36.6 g) as an oil. (Fifth step) 7-Bromo-4-tert-butoxy-2-(ethylsulfanyl)-6-iodo-8-[(1S)-1-phenylethoxy]quinazoline (D7-4, 36.6 g), cyclopropylboronic acid (7.5 g), PdCl(dppf)·CHCl (7.6 g), potassium phosphate tripotassium (53 g), MeCN (440 mL), and water (80 mL) were mixed at room temperature and stirred at 90°C for 4 hours under an argon atmosphere. The reaction mixture was returned to room temperature and then diluted with ethyl acetate and water. The organic and aqueous layers were separated, washed with saturated aqueous sodium chloride, and dried over anhydrous sodium sulfate. After filtration and concentration under reduced pressure, the residue was purified by silica gel column chromatography (hexane / ethyl acetate) to give 7-bromo-4-tert-butoxy-6-cyclopropyl-2-(ethylsulfanyl)-8-[(1S)-1-phenylethoxy]quinazoline (D7-5, 22.9 g) as an oil. (Sixth step) To 7-bromo-4-tert-butoxy-6-cyclopropyl-2-(ethylsulfanyl)-8-[(1S)-1-phenylethoxy]quinazoline (D7-5, 14.21 g), 6-fluoro-5-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2-(triphenylmethyl)-2H-indazole (19.3 g), palladium(II) acetate (0.67 g), dicyclohexyl(2',6'-diisopropoxy-[1,1'-biphenyl]-2-yl)phosphine (2.67 g), anhydrous barium hydroxide (14.6 g), and DOX (500 mL) in water (100 mL) were added. The mixture was degassed and purged with argon gas several times, and then heated and stirred overnight at 50 °C under an argon atmosphere. The cooled reaction suspension was filtered through Celite® while washing with ethyl acetate, and gray insoluble matter was removed by filtration. The filtrate was concentrated under reduced pressure to approximately ¼, then water was added and extracted twice with ethyl acetate. The combined organic layer was washed with saturated aqueous sodium chloride and dried over anhydrous magnesium sulfate. After concentration under reduced pressure, the resulting residue was purified by silica gel column chromatography (hexane / ethyl acetate) to give 4-tert-butoxy-6-cyclopropyl-2-(ethylsulfanyl)-7-[6-fluoro-5-methyl-2-(triphenylmethyl)-2H-indazol-4-yl]-8-[(1S)-1-phenylethoxy]quinazoline (D7-6, approximately 3.3:1 diastereomeric mixture due to axial chirality, 16.44 g) as a solid. (Seventh step) Under a nitrogen atmosphere, 4-tert-butoxy-6-cyclopropyl-2-(ethylsulfanyl)-7-[6-fluoro-5-methyl-2-(triphenylmethyl)-2H-indazol-4-yl]-8-[(1S)-1-phenylethoxy]quinazoline (D7-6, approximately a 3.3:1 diastereomeric mixture due to axial chirality, 33.71 g) was dissolved in CHCl (500 mL). m-Chloroperbenzoic acid (approximately 30% water, 22.4 g) was added under ice-cooling (internal temperature: 5-10 °C) and stirred at room temperature for 2 hours. To the reaction mixture, an aqueous solution (300 mL) of sodium thiosulfate pentahydrate (11 g) and saturated aqueous sodium bicarbonate (300 mL) were poured under ice-cooling. The mixture was stirred at room temperature for 30 minutes and then extracted twice with ethyl acetate. The combined organic layers were washed with saturated aqueous sodium bicarbonate and saturated aqueous sodium chloride, dried over anhydrous magnesium sulfate, filtered, and concentrated under reduced pressure to give 4-tert-butoxy-6-cyclopropyl-2-(ethanesulfonyl)-7-[6-fluoro-5-methyl-2-(triphenylmethyl)-2H-indazol-4-yl]-8-[(1S)-1-phenylethoxy]quinazoline (a diastereomeric mixture resulting from axial chirality). To the resulting residue was added iPrOH (1000 mL) and stirred at room temperature overnight. The resulting solid was collected by filtration, washed with iPrOH, and dried under reduced pressure to give 4-tert-butoxy-6-cyclopropyl-2-(ethanesulfonyl)-7-[6-fluoro-5-methyl-2-(triphenylmethyl)-2H-indazol-4-yl]-8-[(1S)-1-phenylethoxy]quinazoline (a 1:1 diastereomeric mixture due to axial chirality, 11.52 g) as a solid. The filtrate was concentrated under reduced pressure to give the desired (7M)-4-tert-butoxy-6-cyclopropyl-2-(ethanesulfonyl)-7-[6-fluoro-5-methyl-2-(triphenylmethyl)-2H-indazol-4-yl]-8-[(1S)-1-phenylethoxy]quinazoline (D7-7, single diastereomer, 23.29 g) as a solid. (Eighth process) Under a nitrogen atmosphere, 4-methylbenzene-1-sulfonic acid monohydrate (230 mg) was added to a solution of (7M)-4-tert-butoxy-6-cyclopropyl-2-(ethanesulfonyl)-7-[6-fluoro-5-methyl-2-(triphenylmethyl)-2H-indazol-4-yl]-8-[(1S)-1-phenylethoxy]quinazoline (D7-7, 2.00 g) in THF (50 mL) at room temperature, and the mixture was stirred at 50° C. for 1 hour. After the reaction mixture was allowed to cool to room temperature, TEA (350 μL) was added and the mixture was concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (basic silica gel, hexane / ethyl acetate) to give (7M)-4-tert-butoxy-6-cyclopropyl-2-(ethanesulfonyl)-7-(6-fluoro-5-methyl-1H-indazol-4-yl)-8-[(1S)-1-phenylethoxy]quinazoline (D7-8, 740 mg) as a foamy solid. (Ninth step) Under a nitrogen atmosphere, 3,4-dihydro-2H-pyran (900 μL) and 4-methylbenzene-1-sulfonic acid monohydrate (35 mg) were added to a solution of (7M)-4-tert-butoxy-6-cyclopropyl-2-(ethanesulfonyl)-7-(6-fluoro-5-methyl-1H-indazol-4-yl)-8-[(1S)-1-phenylethoxy]quinazoline (D7-8, 735 mg) in THF (10 mL) at room temperature. The mixture was stirred overnight at room temperature and then concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (basic silica gel, hexane / ethyl acetate) to give (7M)-4-tert-butoxy-6-cyclopropyl-2-(ethanesulfonyl)-7-[6-fluoro-5-methyl-1-(oxan-2-yl)-1H-indazol-4-yl]-8-[(1S)-1-phenylethoxy]quinazoline (D7-9, 735 mg) as a foamy solid. (10th step) Under an argon atmosphere, sodium bicarbonate (450 mg) and 10% Pd / C (approximately 50% water content, 250 mg) were added to a solution of (7M)-4-tert-butoxy-6-cyclopropyl-2-(ethanesulfonyl)-7-[6-fluoro-5-methyl-1-(oxan-2-yl)-1H-indazol-4-yl]-8-[(1S)-1-phenylethoxy]quinazoline (D7-9, 730 mg) in MeOH (15 mL) / THF (15 mL) at room temperature. The mixture was stirred overnight under a hydrogen atmosphere at room temperature and atmospheric pressure. After purging with argon, the reaction mixture was filtered through Celite® and washed with ethyl acetate. The filtrate was concentrated under reduced pressure to give (7M)-4-tert-butoxy-6-cyclopropyl-2-(ethanesulfonyl)-7-[6-fluoro-5-methyl-1-(oxan-2-yl)-1H-indazol-4-yl]quinazolin-8-ol (D7-10, 630 mg) as a foamy solid. (Eleventh step) Under a nitrogen atmosphere, (7M)-4-tert-butoxy-6-cyclopropyl-2-(ethanesulfonyl)-7-[6-fluoro-5-methyl-1-(oxan-2-yl)-1H-indazol-4-yl]quinazolin-8-ol (D7-10, 1.4 g) and cesium carbonate (2.4 g) were suspended in DMF (17 mL), and 1-(chloromethyl)-4-ethynylbenzene (500 mg) was added at room temperature and stirred at 60° C. for 1.5 hours. Water (100 mL) was added to the reaction mixture, which was then extracted twice with ethyl acetate. The organic layer was dried over anhydrous magnesium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane / ethyl acetate) to give (7M)-4-tert-butoxy-6-cyclopropyl-2-(ethanesulfonyl)-8-[(4-ethynylphenyl)methoxy]-7-[6-fluoro-5-methyl-1-(oxan-2-yl)-1H-indazol-4-yl]quinazoline (D7-11, 1.47 g) as a foamy solid. (Twelfth step) Under a nitrogen atmosphere, tBuOK (275 mg) was added to a solution of (7M)-4-tert-butoxy-6-cyclopropyl-2-(ethanesulfonyl)-8-[(4-ethynylphenyl)methoxy]-7-[6-fluoro-5-methyl-1-(oxan-2-yl)-1H-indazol-4-yl]quinazoline (D7-11, 1.47 g) and (2S)-2-methoxypropan-1-ol (0.25 mL) in THF (11 mL) while cooling in an ice / MeOH bath (-20 °C to -15 °C), and the mixture was stirred at the same temperature for 30 minutes. Saturated aqueous ammonium chloride was added to the reaction mixture at the same temperature, and the mixture was extracted twice with ethyl acetate. The combined organic layer was washed with water and saturated brine, dried over anhydrous magnesium sulfate, and filtered. The filtrate was concentrated under reduced pressure to give (7M)-4-tert-butoxy-6-cyclopropyl-8-[(4-ethynylphenyl)methoxy]-7-[6-fluoro-5-methyl-1-(oxan-2-yl)-1H-indazol-4-yl]-2-[(2S)-2-methoxypropoxy]quinazoline (D7-12, 1.43 g) as a foamy solid. (13th step) Under a nitrogen atmosphere, 4-methylbenzene-1-sulfonic acid monohydrate (120 mg) was added to a solution of (7M)-4-tert-butoxy-6-cyclopropyl-8-[(4-ethynylphenyl)methoxy]-7-[6-fluoro-5-methyl-1-(oxan-2-yl)-1H-indazol-4-yl]-2-[(2S)-2-methoxypropoxy]quinazoline (D7-12, 1.43 g) in THF (15 mL) at room temperature, and the mixture was stirred at 50°C for 3 hours. The reaction mixture was concentrated under reduced pressure, and the resulting residue was purified by silica gel column chromatography (hexane / ethyl acetate) to give (7M)-6-cyclopropyl-8-[(4-ethynylphenyl)methoxy]-7-[6-fluoro-5-methyl-1-(oxan-2-yl)-1H-indazol-4-yl]-2-[(2S)-2-methoxypropoxy]quinazolin-4-ol (D7-13, 1.05 g) as a foamy solid. (Fourteenth step) Under a nitrogen atmosphere, cesium carbonate (2.68 g) and PyBOP (1.20 g) were added sequentially to a solution of (7M)-6-cyclopropyl-8-[(4-ethynylphenyl)methoxy]-7-[6-fluoro-5-methyl-1-(oxan-2-yl)-1H-indazol-4-yl]-2-[(2S)-2-methoxypropoxy]quinazolin-4-ol (D7-13, 1.05 g) in THF (15 mL) at room temperature, and the mixture was stirred for 1 hour. (3S)-tert-Butyl 3-(methylamino)pyrrolidine-1-carboxylate (0.94 mL) was added at room temperature, and the mixture was stirred overnight at 60 °C. Ethyl acetate was added to the reaction mixture, and the insoluble matter was filtered through Celite®. The filtrate was concentrated under reduced pressure, and the resulting residue was purified by silica gel column chromatography (basic silica gel, hexane / ethyl acetate) to give (3S)-3-[{(7M)-6-cyclopropyl-8-[(4-ethynylphenyl)methoxy]-7-[6-fluoro-5-methyl-1-(oxan-2-yl)-1H-indazol-4-yl]-2-[(2S)-2-methoxypropoxy]quinazolin-4-yl}(methyl)amino]pyrrolidine-1-carboxylate tert-butyl ester (D7-14, 1.62 g) as an oil. (15th process) Under an argon atmosphere, a solution of (4R)-1-[(2S)-2-azido-3-methylbutanoyl]-4-hydroxy-N-{(1R)-2-hydroxy-1-[4-(4-methyl-1,3-thiazol-5-yl)phenyl]ethyl}-L-prolinamide (75 mg) and tert-butyl (3S)-3-[{(7M)-6-cyclopropyl-8-[(4-ethynylphenyl)methoxy]-7-[6-fluoro-5-methyl-1-(oxan-2-yl)-1H-indazol-4-yl]-2-[(2S)-2-methoxypropoxy]quinazolin-4-yl}(methyl)amino]pyrrolidine-1-carboxylate (D7-14, 230 mg) in tBuOH / THF / water (1:1:1 mixture, 2.0 mL) was added with anhydrous copper(II) sulfate (10 To the reaction mixture were added ethylenediaminetetraacetic acid disodium salt (175 mg) at room temperature and stirred at the same temperature for 1 hour. To the reaction mixture were added water and CHCl3 / MeOH (9 / 1). The aqueous and organic layers were separated, and the aqueous layer was extracted with CHCl3 / MeOH (9 / 1). The combined organic layers were dried over anhydrous sodium sulfate and filtered, and the filtrate was concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (basic silica gel, CHCl3 / MeOH) to afford tert-butyl (3S)-3-[{(7M)-6-cyclopropyl-7-[6-fluoro-5-methyl-1-(oxan-2-yl)-1H-indazol-4-yl]-8-{[4-(1-{(2S)-1-[(2S,4R)-4-hydroxy-2-({(1R)-2-hydroxy-1-[4-(4-methyl-1,3-thiazol-5-yl)phenyl]ethyl}carbamoyl)pyrrolidin-1-yl]-3-methyl-1-oxobutan-2-yl}-1H-1,2,3-triazol-4-yl)phenyl]methoxy}-2-[(2S)-2-methoxypropoxy]quinazolin-4-yl}(methyl)amino]pyrrolidine-1-carboxylate (D7-15, 197 mg) was obtained as a foamy solid. (16th step) tert-Butyl (3S)-3-[{(7M)-6-cyclopropyl-7-[6-fluoro-5-methyl-1-(oxan-2-yl)-1H-indazol-4-yl]-8-{[4-(1-{(2S)-1-[(2S,4R)-4-hydroxy-2-({(1R)-2-hydroxy-1-[4-(4-methyl-1,3-thiazol-5-yl)phenyl]ethyl}carbamoyl)pyrrolidin-1-yl]-3-methyl-1-oxobutan-2-yl}-1H-1,2,3-triazol-4-yl)phenyl]methoxy}-2-[(2S)-2-methoxypropoxy]quinazolin-4-yl}(methyl)amino]pyrrolidine-1-carboxylate (D7-15, 197 mg) was dissolved in CHCl (2 To a solution of 100 mL of 1,000 sachets ... The combined organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure to give (4R)-1-[(2S)-2-{4-[4-({[(7M)-6-cyclopropyl-7-(6-fluoro-5-methyl-1H-indazol-4-yl)-2-[(2S)-2-methoxypropoxy]-4-{methyl[(3S)-pyrrolidin-3-yl]amino}quinazolin-8-yl]oxy}methyl)phenyl]-1H-1,2,3-triazol-1-yl}-3-methylbutanoyl]-4-hydroxy-N-{(1R)-2-hydroxy-1-[4-(4-methyl-1,3-thiaazol-5-yl)phenyl]ethyl}-L-prolinamide (D7, 65 mg) as a foamy solid. Synthesis of drug D8 (First step) A solution of (4R)-1-[(2S)-2-azido-3-methylbutanoyl]-N-{(1R)-1-[4-(1-ethyl-1H-pyrazol-5-yl)phenyl]-2-hydroxyethyl}-4-hydroxy-L-prolinamide (80 mg), tert-butyl (3S)-3-[{(7M)-6-cyclopropyl-8-[(4-ethynylphenyl)methoxy]-7-[6-fluoro-5-methyl-1-(oxan-2-yl)-1H-indazol-4-yl]-2-[(2S)-2-methoxypropoxy]quinazolin-4-yl}(methyl)amino]pyrrolidine-1-carboxylate (D7-14, 125 mg) in tBuOH / THF / water (1:1:1 mixture, 2.0 mL) was added with anhydrous copper(II) sulfate (10 To the reaction mixture, ethylenediaminetetraacetic acid disodium salt (175 mg) was added at room temperature, and the mixture was stirred at the same temperature for 30 minutes. Water was added to the reaction mixture and stirred, and the resulting insoluble matter was filtered off to obtain (3S)-3-[{(7M)-6-cyclopropyl-8-{[4-(1-{(2S)-1-[(2S,4R)-2-({(1R)-1-[4-(1-ethyl-1H-pyrazol-5-yl)phenyl]-2-hydroxyethyl}carbamoyl)-4-hydroxypyrrolidin-1-yl]-3-methyl-1-oxobutan-2-yl}-1H-1,2,3-triazol-4-yl)phenyl]methoxy}-7-[6-fluoro-5-methyl-1-(oxan-2-yl)-1H-indazol-4-yl]-2-[(2S)-2-methoxypropoxy]quinazolin-4-yl}(methyl)amino]pyrrolidine-1-carboxylate tert-butyl ester (D8-1, 225 mg) as a solid. (Second process) To a solution of tert-butyl (3S)-3-[{(7M)-6-cyclopropyl-8-{[4-(1-{(2S)-1-[(2S,4R)-2-({(1R)-1-[4-(1-ethyl-1H-pyrazol-5-yl)phenyl]-2-hydroxyethyl}carbamoyl)-4-hydroxypyrrolidin-1-yl]-3-methyl-1-oxobutan-2-yl}-1H-1,2,3-triazol-4-yl)phenyl]methoxy}-7-[6-fluoro-5-methyl-1-(oxan-2-yl)-1H-indazol-4-yl]-2-[(2S)-2-methoxypropoxy]quinazolin-4-yl}(methyl)amino]pyrrolidine-1-carboxylate (D8-1, 224 mg) in CHCl (1 mL) was added TFA (1 (mL) was added at room temperature. The mixture was stirred at room temperature for 2 hours. The reaction solvent was concentrated under reduced pressure, and MeCN, saturated aqueous sodium bicarbonate solution, and water were added to the residue, followed by stirring at room temperature for 20 minutes. The resulting suspension was purified by ODS column chromatography (MeCN / 0.1% aqueous formic acid solution), and the desired fraction was concentrated under reduced pressure. The residue was dissolved in CHCl3 / iPrOH (9 / 1), saturated aqueous sodium bicarbonate solution was added, and the mixture was extracted twice with CHCl3 / MeOH (5 / 1). The combined organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure to give (4R)-1-[(2S)-2-{4-[4-({[(7M)-6-cyclopropyl-7-(6-fluoro-5-methyl-1H-indazol-4-yl)-2-[(2S)-2-methoxypropoxy]-4-{methyl[(3S)-pyrrolidin-3-yl]amino}quinazolin-8-yl]oxy}methyl)phenyl]-1H-1,2,3-triazol-1-yl}-3-methylbutanoyl]-N-{(1R)-1-[4-(1-ethyl-1H-pyrazol-5-yl)phenyl]-2-hydroxyethyl}-4-hydroxy-L-prolinamide (D8, 109 mg) as a foamy solid. Synthesis of drug D9 (First step) To a mixture of tert-butyl (1S,4S)-5-[7-bromo-2-(ethylsulfanyl)-8-fluoro-6-iodoquinazolin-4-yl]-2,5-diazabicyclo[2.2.1]heptane-2-carboxylate (40.2 g), anhydrous THF (400 mL), and (1S)-1-phenylethan-1-ol (10 mL) was added tBuOK (15.3 g), and the mixture was stirred under argon atmosphere for 30 minutes under cooling and at room temperature for 30 minutes. Ice and saturated aqueous ammonium chloride solution were poured into the reaction mixture, which was then extracted twice with ethyl acetate. The combined organic layers were washed with saturated aqueous sodium chloride, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure to give tert-butyl (1S,4S)-5-{7-bromo-2-(ethylsulfanyl)-6-iodo-8-[(1S)-1-phenylethoxy]quinazolin-4-yl}-2,5-diazabicyclo[2.2.1]heptane-2-carboxylate (D9-1, 45.94 g) as a foamy solid. (Second process) A mixture of tert-butyl (1S,4S)-5-{7-bromo-2-(ethylsulfanyl)-6-iodo-8-[(1S)-1-phenylethoxy]quinazolin-4-yl}-2,5-diazabicyclo[2.2.1]heptane-2-carboxylate (D9-1, 45.93 g), cyclopropylboronic acid (9.8 g), tripotassium phosphate (55 g), PdCl(dppf)·CHCl (5.4 g), MeCN (360 mL), DOX (240 mL), and water (120 mL) was degassed and purged with argon gas, and stirred at 90 °C under an argon atmosphere for 5 h. The cooled reaction mixture was concentrated under reduced pressure to approximately half its volume. The residue was poured into saturated aqueous sodium bicarbonate (100 mL) and water (300 mL), and extracted twice with ethyl acetate. The combined organic layers were washed with saturated aqueous sodium chloride, followed by the addition of thiol-modified silica gel (approximately 10 g) and basic silica gel (approximately 10 g) and stirring at room temperature for 30 minutes. The insoluble material was removed by filtration while washing with ethyl acetate, and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane / ethyl acetate) to afford tert-butyl (1S,4S)-5-{7-bromo-6-cyclopropyl-2-(ethylsulfanyl)-8-[(1S)-1-phenylethoxy]quinazolin-4-yl}-2,5-diazabicyclo[2.2.1]heptane-2-carboxylate (D9-2, 27.74 g) as a foamy solid. (Third step) tert-Butyl (1S,4S)-5-{7-bromo-6-cyclopropyl-2-(ethylsulfanyl)-8-[(1S)-1-phenylethoxy]quinazolin-4-yl}-2,5-diazabicyclo[2.2.1]heptane-2-carboxylate (D9-2, 17.7 g), 6-fluoro-5-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2-(triphenylmethyl)-2H-indazole (19.6 g), palladium(II) acetate (0.7 g), dicyclohexyl(2',6'-diisopropoxy-[1,1'-biphenyl]-2-yl)phosphine (2.7 g), barium hydroxide (14.6 g), DOX (500 mL), water (50 A mixture of 10 mL of ethanol (2 mL) was degassed, purged with argon gas, and stirred at 50°C under an argon atmosphere for 6 hours. The cooled reaction suspension was filtered through Celite (registered trademark) while washing with ethyl acetate. The filtrate was concentrated under reduced pressure to about one-quarter of its original volume, and then water was poured into it, followed by extraction twice with ethyl acetate. The combined organic layers were washed with saturated aqueous sodium chloride and then dried over anhydrous magnesium sulfate. The mixture was concentrated under reduced pressure, and the residue was purified twice by silica gel column chromatography (basic silica gel, hexane / ethyl acetate) to give (1S,4S)-5-{6-cyclopropyl-2-(ethylsulfanyl)-7-[6-fluoro-5-methyl-2-(triphenylmethyl)-2H-indazol-4-yl]-8-[(1S)-1-phenylethoxy]quinazolin-4-yl}-2,5-diazabicyclo[2.2.1]heptane-2-carboxylate tert-butyl ester (D9-3, approximately 4.5:1 mixture of isomers with respect to axial chirality, 20.64 g) as a foamy solid. (Fourth step) To a mixture of tert-butyl (1S,4S)-5-{6-cyclopropyl-2-(ethylsulfanyl)-7-[6-fluoro-5-methyl-2-(triphenylmethyl)-2H-indazol-4-yl]-8-[(1S)-1-phenylethoxy]quinazolin-4-yl}-2,5-diazabicyclo[2.2.1]heptane-2-carboxylate (D9-3, approximately 4.5:1 isomer mixture with respect to axial chirality, 20.63 g) and EtOH (250 mL), 4-methylbenzene-1-sulfonic acid monohydrate (4.8 g) was added with stirring at room temperature. The mixture was stirred at room temperature for 1 hour under an argon atmosphere. Ice and saturated aqueous sodium bicarbonate were poured into the reaction mixture, and the resulting white insoluble matter was dissolved in ethyl acetate and extracted twice with ethyl acetate. The combined organic layer was washed with saturated aqueous sodium chloride, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane / ethyl acetate) to give (1S,4S)-5-{(7M)-6-cyclopropyl-2-(ethylsulfanyl)-7-(6-fluoro-5-methyl-1H-indazol-4-yl)-8-[(1S)-1-phenylethoxy]quinazolin-4-yl}-2,5-diazabicyclo[2.2.1]heptane-2-carboxylate tert-butyl ester (D9-4, single isomer with respect to axial asymmetry, 11.17 g) as a foamy solid. (Fifth step) To a mixture of tert-butyl (1S,4S)-5-{(7M)-6-cyclopropyl-2-(ethylsulfanyl)-7-(6-fluoro-5-methyl-1H-indazol-4-yl)-8-[(1S)-1-phenylethoxy]quinazolin-4-yl}-2,5-diazabicyclo[2.2.1]heptane-2-carboxylate (D9-4, 11.1 g) and THF (150 mL), 3,4-dihydro-2H-pyran (10 mL) and 4-methylbenzene-1-sulfonic acid monohydrate (0.7 g) were added with stirring at room temperature under an argon atmosphere for 14 hours. 3,4-Dihydro-2H-pyran (5 mL) and 4-methylbenzene-1-sulfonic acid monohydrate (0.3 g) were added, and the mixture was stirred at room temperature for an additional 5 hours. The reaction was quenched with triethyl ether (TEA) (2 mL) and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane / ethyl acetate) to give tert-butyl (1S,4S)-5-{(7M)-6-cyclopropyl-2-(ethylsulfanyl)-7-[6-fluoro-5-methyl-1-(oxan-2-yl)-1H-indazol-4-yl]-8-[(1S)-1-phenylethoxy]quinazolin-4-yl}-2,5-diazabicyclo[2.2.1]heptane-2-carboxylate (D9-5, 11.15 g) as a foamy solid. (Sixth step) To a mixture of tert-butyl (1S,4S)-5-{(7M)-6-cyclopropyl-2-(ethylsulfanyl)-7-[6-fluoro-5-methyl-1-(oxan-2-yl)-1H-indazol-4-yl]-8-[(1S)-1-phenylethoxy]quinazolin-4-yl}-2,5-diazabicyclo[2.2.1]heptane-2-carboxylate (D9-5, 11.14 g) and CHCl (170 mL), m-chloroperbenzoic acid (approximately 30% aqueous, 7.9 g) was added under ice cooling and stirred at room temperature for 1.5 hours under an argon atmosphere. Ice, saturated aqueous sodium thiosulfate, and saturated aqueous sodium bicarbonate were added, and the mixture was stirred at room temperature for approximately 20 minutes. The reaction mixture was then diluted with CHCl and separated. The organic layer was dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane / ethyl acetate) and (1S,4S)-5-{(7M)-6-cyclopropyl-2-(ethanesulfonyl)-7-[6-fluoro-5-methyl-1-(oxan-2-yl)-1H-indazol-4-yl]-8-[(1S)-1-phenylethoxy]quinazolin-4-yl}-2,5-diazabicyclo[2.2.1]heptane-2-carboxylate tert-butyl ester (D9-6, 9.02 g) was obtained as a foamy solid. (Seventh step) To a mixture of tert-butyl (1S,4S)-5-{(7M)-6-cyclopropyl-2-(ethanesulfonyl)-7-[6-fluoro-5-methyl-1-(oxan-2-yl)-1H-indazol-4-yl]-8-[(1S)-1-phenylethoxy]quinazolin-4-yl}-2,5-diazabicyclo[2.2.1]heptane-2-carboxylate (D9-6, 4.5 g) and MeOH (100 mL), 10% Pd / C (52% aqueous, 1 g) was added and stirred overnight at room temperature under a hydrogen atmosphere. The mixture was filtered through Celite®, washing with ethyl acetate and CHCl3. Toluene (approximately 20 mL) was added to the filtrate and concentrated under reduced pressure. MeOH (80 mL) and 10% Pd / C (52% aqueous, 1.4 g) were added to the resulting solid and stirred at room temperature for 3 hours under atmospheric hydrogen atmosphere. Celite® was added and the mixture was filtered, washing with ethyl acetate and CHCl3. The filtrate was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (hexane / ethyl acetate) to give tert-butyl (1S,4S)-5-{(7M)-6-cyclopropyl-2-(ethanesulfonyl)-7-[6-fluoro-5-methyl-1-(oxan-2-yl)-1H-indazol-4-yl]-8-hydroxyquinazolin-4-yl}-2,5-diazabicyclo[2.2.1]heptane-2-carboxylate (D9-7, 3.42 g) as a foamy solid. (Eighth process) To a mixture of tert-butyl (1S,4S)-5-{(7M)-6-cyclopropyl-2-(ethanesulfonyl)-7-[6-fluoro-5-methyl-1-(oxan-2-yl)-1H-indazol-4-yl]-8-hydroxyquinazolin-4-yl}-2,5-diazabicyclo[2.2.1]heptane-2-carboxylate (D9-7, 3.01 g), DMF (30 mL), and methyl 4-(chloromethyl)benzoate (1 g) was added cesium carbonate (4 g) while stirring at room temperature. The mixture was stirred overnight under an argon atmosphere. The reaction mixture was poured into ice water and saturated aqueous ammonium chloride, and extracted twice with ethyl acetate. The combined organic layer was washed with saturated aqueous sodium chloride and dried over anhydrous magnesium sulfate. Concentrated under reduced pressure, the resulting residue was purified by silica gel column chromatography (basic silica gel, hexane / ethyl acetate) and (1S,4S)-5- [(7M)-6-cyclopropyl-2- (ethanesulfonyl) -7- [6-fluoro-5-methyl-1- (oxan-2-yl) -1H-indazol-4-yl] -8- { [4- (methoxycarbonyl) phenyl] methoxy} quinazolin-4-yl] -2,5-diazabicyclo [2.2.1] heptane-2-carboxylate tert- butyl (D9-8, 3.32 g) was obtained as a foamy solid. (Ninth step) To a mixture of tert-butyl (1S,4S)-5-[(7M)-6-cyclopropyl-2-(ethanesulfonyl)-7-[6-fluoro-5-methyl-1-(oxan-2-yl)-1H-indazol-4-yl]-8-{[4-(methoxycarbonyl)phenyl]methoxy}quinazolin-4-yl]-2,5-diazabicyclo[2.2.1]heptane-2-carboxylate (D9-8, 200 mg), tetrahydro-2H-pyran-4-ol (32 mg), and THF (4 mL) was added tBuOK (56 mg) under cooling in an ice / MeOH bath and stirred at the same temperature for 30 minutes under an argon atmosphere. The reaction mixture was poured into ice water and saturated aqueous ammonium chloride solution and extracted twice with ethyl acetate. The combined organic layer was washed with saturated aqueous sodium chloride solution and dried over anhydrous magnesium sulfate. Concentrated under reduced pressure, the residue was purified by silica gel column chromatography (basic silica gel, hexane / ethyl acetate) and (1S,4S)-5-{(7M)-6-cyclopropyl-7-[6-fluoro-5-methyl-1-(oxan-2-yl)-1H-indazol-4-yl]-8-{[4-(methoxycarbonyl)phenyl]methoxy}-2-[(oxan-4-yl)oxy]quinazolin-4-yl}-2,5-diazabicyclo[2.2.1]heptane-2-carboxylate tert-butyl (D9-9, 144 mg) was obtained as a foamy solid. (10th step) To a mixture of tert-butyl (1S,4S)-5-{(7M)-6-cyclopropyl-7-[6-fluoro-5-methyl-1-(oxan-2-yl)-1H-indazol-4-yl]-8-{[4-(methoxycarbonyl)phenyl]methoxy}-2-[(oxan-4-yl)oxy]quinazolin-4-yl}-2,5-diazabicyclo[2.2.1]heptane-2-carboxylate (D9-9, 142 mg), MeOH (1 mL), and THF (1 mL) was added aqueous sodium hydroxide (1 M, 1 mL) under ice cooling and stirred at room temperature for 6 hours. Hydrochloric acid (1 M, 1 mL) was added under ice cooling, and the mixture was extracted twice with CHCl3 / MeOH (9 / 1). The combined organic layer was dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure to give 4-[({(7M)-4-[(1S,4S)-5-(tert-butoxycarbonyl)-2,5-diazabicyclo[2.2.1]heptan-2-yl]-6-cyclopropyl-7-[6-fluoro-5-methyl-1-(oxan-2-yl)-1H-indazol-4-yl]-2-[(oxan-4-yl)oxy]quinazolin-8-yl}oxy)methyl]benzoic acid (D9-10, 132 mg) as a solid. (Eleventh step) To a solution of 3-hydroxy-1-[(4-methoxyphenyl)methyl]piperidine-2,6-dione (800 mg) in CHCl (10 mL) was added trifluoromethanesulfonic anhydride (809 μL) and pyridine (520 μL) under ice-cooling under an argon atmosphere, and the mixture was stirred at the same temperature for 1 hour. The mixture was concentrated under reduced pressure, and the resulting residue was purified by silica gel column chromatography (hexane / ethyl acetate) to give 1-[(4-methoxyphenyl)methyl]-2,6-dioxopiperidin-3-yl trifluoromethanesulfonate (D9-11, 1.1 g) as an oil. (Twelfth step) Under an argon atmosphere, tBuOK (260 mg) was added to a solution of 6-bromo-1-methyl-1,3-dihydro-2H-benzimidazol-2-one (350 mg) in THF (20 mL) while cooling in an ice / sodium chloride bath, and the mixture was stirred at the same temperature for 30 minutes. A solution of 1-[(4-methoxyphenyl)methyl]-2,6-dioxopiperidin-3-yl trifluoromethanesulfonate (D9-11, 700 mg) in THF (7 mL) was added dropwise over 10 minutes, and the mixture was stirred at the same temperature for 30 minutes. Water was added to the reaction mixture, and the mixture was extracted three times with ethyl acetate. The combined organic layer was washed with saturated aqueous sodium chloride, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The resulting solid was collected by filtration, washed with ethyl acetate, and dried under reduced pressure to give 3-(5-bromo-3-methyl-2-oxo-2,3-dihydro-1H-benzimidazol-1-yl)-1-[(4-methoxyphenyl)methyl]piperidine-2,6-dione (D9-12, 524 mg) as a solid. (13th step) Trifluoroacetic acid (5 mL) and trifluoromethanesulfonic acid (5 mL) were added to 3-(5-bromo-3-methyl-2-oxo-2,3-dihydro-1H-benzimidazol-1-yl)-1-[(4-methoxyphenyl)methyl]piperidine-2,6-dione (D9-12, 500 mg), and the mixture was stirred at 60°C for 1 hour. The mixture was concentrated under reduced pressure until the liquid volume was reduced to about half, and ethyl acetate was added. The mixture was poured into a saturated aqueous solution of sodium bicarbonate under ice cooling and stirred for a while. The organic layer was separated, and the aqueous layer was extracted with ethyl acetate. The combined organic layers were washed with a saturated aqueous solution of sodium chloride, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (hexane / ethyl acetate) to give 3-(5-bromo-3-methyl-2-oxo-2,3-dihydro-1H-benzimidazol-1-yl)piperidine-2,6-dione (D9-13, 300 mg) as a solid. (Fourteenth step) Under an argon atmosphere, a mixture of 3-(5-bromo-3-methyl-2-oxo-2,3-dihydro-1H-benzimidazol-1-yl)piperidine-2,6-dione (D9-13, 4.32 g), potassium vinyltrifluoroborate (7.5 g), PdCl(dppf)·CHCl (1.16 g), cesium carbonate (9.2 g), DOX (50 mL), and water (5 mL) was stirred at 80 °C for 3 h. Ethyl acetate and water were added, and the mixture was filtered through Celite®. The two layers were separated, and the aqueous layer was extracted with ethyl acetate. The combined organic layer was washed with saturated aqueous sodium chloride, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The product was purified by silica gel column chromatography (hexane / ethyl acetate). The resulting solid was collected by filtration, washing with iPr2O, and dried under reduced pressure to give 3-(5-ethenyl-3-methyl-2-oxo-2,3-dihydro-1H-benzimidazol-1-yl)piperidine-2,6-dione (D9-14, 559 mg) as a solid. ...

Claims

1. An antibody-drug conjugate of formula (I) or a salt thereof (Wherein, Ab is an antibody or an antigen-binding fragment thereof, D is a heterocyclic compound having an activity of inducing degradation of G12D mutant KRAS protein, and L A is a linker for linking Ab and D, and n is a number from 1 to 20.

2. D is a heterocyclic compound represented by formula (II), A is CR A or N, R A is H, cyano, or optionally substituted C 1-３ alkyl, Q is CR Q or N, R Q H, halogen, C 3-６ Cycloalkyl, vinyl, or optionally substituted C 1-３ alkyl, E is CH or N, R 1 is cyano, OH, halogen, and optionally substituted C 1-３ naphthyl optionally substituted with one or two groups selected from the group consisting of alkyl, or a group selected from the group consisting of the following formulae (III), (IV) and (V): R 1a , R 1b and R 1c are each independently H, vinyl, halogen, or optionally substituted C 1-３ alkyl, R 2 -V １ -V 2 or W, V 1 is a bond, -CH2-, -O-, -S- or -N(R V1 )- and R V1 is H or optionally substituted C 1-３ is alkyl, V 2 is a group selected from the group consisting of the following formulas (VI) and (VII): W is a group selected from the group consisting of the following formulas (VIII), (IX), (X), (XI), (XII), (XIII), (XIV), (XV) and (XVI), R 2a are each independently OH, OCH3, F or optionally substituted C 1-３ alkyl, 2a is bonded only to a carbon atom that is a constituent atom of a ring selected from the group consisting of an azetidine ring represented by formula (VI), a pyrrolidine ring represented by formula (VII), a piperidine ring represented by formula (VIII), and a piperazine ring represented by formula (IX), m is an integer of 0 to 2, R 3 is optionally substituted C 1-6 alkyl, optionally substituted heterocycloalkyl, or optionally substituted heteroaryl; X is a bond, -CH2-, -O-, -S-, or -NR 4X - and R 4X is H or optionally substituted C 1-３ is alkyl, Y 1 is -O-(optionally substituted C 1-３ Alkylene)- ＊Y2 , -S-(optionally substituted C 1-３ Alkylene)- ＊Y2 , -SO2-(optionally substituted C 1-３ Alkylene)- ＊Y2 , -NR Y -(optionally substituted C 1-３ Alkylene)- ＊Y2 , -(optionally substituted C 1-３ Alkylene)-O- ＊Y2 , -(optionally substituted C 1-３ Alkylene)-S- ＊Y2 , -(optionally substituted C 1-３ Alkylene)-SO2- ＊Y2 or -(optionally substituted C 1-３ (alkylene)-NR Y - ＊Y2 And ( ＊Y2 is Y 2 ), R Y is H or optionally substituted C 1-３ is alkyl, Y 2 is a bond, optionally substituted phenylene or optionally substituted heteroarylene; L P is Y 2 and a group that chemically bonds EUB to L, wherein EUB is a group capable of binding to an E3 ubiquitin ligase selected from the group consisting of VHL, cereblon, IAP, MDM2, DCAF11, DCAF15, DCAF16, BIRC2, KEAP1, RNF4, RNF114, FEM1B, and AhR, A is a linker for connecting Ab to D, where L A The compound or salt thereof according to claim 1 , wherein 3. V 2 is a group selected from the group consisting of the following formula (VIa) and formula (VIIa): *LA L A ) W is a group selected from the group consisting of the following formulas (VIIIa), (IXa), (Xa), (XIa), (XIIa), (XIIIa), (XIVa), (XVa) and (XVIa): *LA L A ) L A is a linker for connecting Ab to D, where L A is V 2 or a nitrogen atom contained in W *LA The antibody-drug conjugate or salt thereof according to claim 2, which binds to D at a binding site represented by 4. A is N and Q is CR Q and R Q is cyclopropyl, E is CH, and R 1 is represented by the following formula (III-2), R 2 But -V 1 -V 2 or W, V 1 is -N(CH3)-, V 2 is represented by the following formula (VII-2), W is represented by the following formula (XIV): R 3 is n-propyl optionally substituted with -OCH3, or tetrahydropyranyl; X is -O-; Y 1 But -O-(methylene)- ＊Y2 And ( ＊Y2 is Y 2 ), Y 2 is phenylene, L P But, Y 2 and EUB is a group capable of binding to an E3 ubiquitin ligase selected from the group consisting of VHL and cereblon.

5. V 2 is represented by the following formula (VII-2a) ( *LA L A ) W is represented by the following formula (XIVa): *LA L A ) L A is a linker for connecting Ab to D, where L A is V 2 or a nitrogen atom contained in W *LA The antibody-drug conjugate or salt thereof according to claim 4, which binds to D at a binding site represented by 6. D is (4R)-1-[(2S)-2-(4-{4-[({6-cyclopropyl-4-[(1S,4S)-2,5-diazabicyclo[2.2.1]heptan-2-yl]-7-(6-fluoro-5-methyl-1H-indazol-4-yl)-2-[(oxan-4-yl)oxy]quinazolin-8-yl}oxy)methyl]phenyl}-1H-1,2,3-triazol-1-yl)-3-methylbutanoyl]-4-hydroxy-N-{(1R)-2-hydroxy-1-[4-(4-methyl-1,3-thiazol-5-yl)phenyl]ethyl}-L-prolinamide; (4R)-1-[(2S)-2-(4-{4-[({6-cyclopropyl-4-[(1S,4S)-2,5-diazabicyclo[2.2.1]heptan-2-yl]-7-(6-fluoro-5-methyl-1H-indazol-4-yl)-2-[(oxan-4-yl)oxy]quinazolin-8-yl}oxy)methyl]phenyl}-1H-1,2,3-triazol-1-yl)-3-methylbutanoyl]-4-hydroxy-N-{(1R)-2-hydroxy-1-[4-(2-oxo-1,3-oxazolidin-3-yl)phenyl]ethyl}-L-prolinamide, (4R)-1-[(2S)-2-(4-{4-[({6-cyclopropyl-4-[(1S,4S)-2,5-diazabicyclo[2.2.1]heptan-2-yl]-7-(6-fluoro-5-methyl-1H-indazol-4-yl)-2-[(oxan-4-yl)oxy]quinazolin-8-yl}oxy)methyl]phenyl}-1H-1,2,3-triazol-1-yl)-3-methylbutanoyl]-4-hydroxy-N-{(1R)-2-hydroxy-1-[4-(1-methyl-1H-pyrazol-5-yl)phenyl]ethyl}-L-prolinamide, (4R)-1-[(2S)-2-(4-{4-[({6-cyclopropyl-4-[(1S,4S)-2,5-diazabicyclo[2.2.1]heptan-2-yl]-7-(6-fluoro-5-methyl-1H-indazol-4-yl)-2-[(2S)-2-methoxypropoxy]quinazolin-8-yl}oxy)methyl]phenyl}-1H-1,2,3-triazol-1-yl)-3-methylbutanoyl]-4-hydroxy-N-{(1R)-2-hydroxy-1-[4-(4-methyl-1,3-thiazol-5-yl)phenyl]ethyl}-L-prolinamide, (4R)-1-[(2S)-2-(4-{4-[({6-cyclopropyl-4-[(1S,4S)-2,5-diazabicyclo[2.2.1]heptan-2-yl]-7-(6-fluoro-5-methyl-1H-indazol-4-yl)-2-[(2S)-2-methoxypropoxy]quinazolin-8-yl}oxy)methyl]phenyl}-1H-1,2,3-triazol-1-yl)-3-methylbutanoyl]-N-{(1R)-1-[4-(1-ethyl-1H-pyrazol-5-yl)phenyl]-2-hydroxyethyl}-4-hydroxy-L-prolinamide, (4R)-1-[(2S)-2-(4-{4-[({6-cyclopropyl-4-[(1S,4S)-2,5-diazabicyclo[2.2.1]heptan-2-yl]-7-(6-fluoro-5-methyl-1H-indazol-4-yl)-2-[(2S)-2-methoxypropoxy]quinazolin-8-yl}oxy)methyl]phenyl}-1H-1,2,3-triazol-1-yl)-3-methylbutanoyl]-4-hydroxy-N-{(1R)-2-hydroxy-1-[4-(4-methyl-1,3-oxazol-5-yl)phenyl]ethyl}-L-prolinamide, (4R)-1-[(2S)-2-{4-[4-({[(7M)-6-cyclopropyl-7-(6-fluoro-5-methyl-1H-indazol-4-yl)-2-[(2S)-2-methoxypropoxy]-4-{methyl[(3S)-pyrrolidin-3-yl]amino}quinazolin-8-yl]oxy}methyl)phenyl]-1H-1,2,3-triazol-1-yl}-3-methylbutanoyl]-4-hydroxy-N-{(1R)-2-hydroxy-1-[4-(4-methyl-1,3-thiazol-5-yl)phenyl]ethyl}-L-prolinamide, (4R)-1-[(2S)-2-{4-[4-({[(7M)-6-cyclopropyl-7-(6-fluoro-5-methyl-1H-indazol-4-yl)-2-[(2S)-2-methoxypropoxy]-4-{methyl[(3S)-pyrrolidin-3-yl]amino}quinazolin-8-yl]oxy}methyl)phenyl]-1H-1,2,3-triazol-1-yl}-3-methylbutanoyl]-N-{(1R)-1-[4-(1-ethyl-1H-pyrazol-5-yl)phenyl]-2-hydroxyethyl}-4-hydroxy-L-prolinamide, 3-(5-{[(3S)-4-{4-[({(7M)-6-cyclopropyl-4-[(1S,4S)-2,5-diazabicyclo[2.2.1]heptan-2-yl]-7-(6-fluoro-5-methyl-1H-indazol-4-yl)-2-[(oxan-4-yl)oxy]quinazolin-8-yl}oxy)methyl]benzoyl}-3-methylpiperazin-1-yl]methyl}-3-methyl-2-oxo-2,3-dihydro-1H-benzimidazol-1-yl)piperidine-2,6-dione, 1-(6-{[(3S)-4-{4-[({(7M)-6-cyclopropyl-4-[(1S,4S)-2,5-diazabicyclo[2.2.1]heptan-2-yl]-7-(6-fluoro-5-methyl-1H-indazol-4-yl)-2-[(oxan-4-yl)oxy]quinazolin-8-yl}oxy)methyl]benzoyl}-3-methylpiperazin-1-yl]methyl}-1-methyl-1H-indazol-3-yl)-1,3-diazinan-2,4-dione, or 3-(5-{[(3S)-4-{4-[({(7M)-6-cyclopropyl-4-[(1S,4S)-2,5-diazabicyclo[2.2.1]heptan-2-yl]-7-(6-fluoro-5-methyl-1H-indazol-4-yl)-2-[(2S)-2-methoxypropoxy]quinazolin-8-yl}oxy)methyl]benzoyl}-3-methylpiperazin-1-yl]methyl}-3-methyl-2-oxo-2,3-dihydro-1H-benzimidazol-1-yl)piperidine-2,6-dione, or The antibody-drug conjugate or salt thereof according to any one of claims 1 and 2, wherein phosphate = dihydrogen = (2R)-2-({(4R)-1-[(2S)-2-{4-[4-({[(7M)-6-cyclopropyl-7-(6-fluoro-5-methyl-1H-indazol-4-yl)-2-[(2S)-2-methoxypropoxy]-4-{methyl[(3S)-pyrrolidin-3-yl]amino}quinazolin-8-yl]oxy}methyl)phenyl]-1H-1,2,3-triazol-1-yl}-3-methylbutanoyl]-4-hydroxy-L-prolyl}amino)-2-[4-(1H-1,2,4-triazol-1-yl)phenyl]ethyl.

7. L A is a linker represented by formula (XXVIII): (wherein, Str is a stretcher unit and binds to Ab and CLL, r is 0 or 1, CLL is a moiety that is cleavable in vivo, Sp is a spacer unit and binds to CLL and D, t is 0 or 1, *Ab indicates the binding site with Ab).

8. The antibody-drug conjugate or salt thereof according to claim 7, wherein Str is a stretcher unit represented by formula (ST-1) and r is 1. (In the formula, R st1 is optionally substituted C 1-12 Alkylene, -(CH2CH2O) a1 -C 1-6 Alkylene-, -C 1-6 Alkylene-(OCH2CH2) a2 -, -Optionally substituted C 1-6 Alkylene-NH-C(=O)-optionally substituted C 1-6 Alkylene-, -optionally substituted C 1-6 Alkylene-C(=O)-NH-optionally substituted C 1-6 Alkylene-, optionally substituted C 1-6 Alkylene-C(=O)-NH-(CH2CH2O) a3 -C 1-6 Alkylene- or optionally substituted C 1-6 Alkylene-NH-C(=O)-(CH2CH2O) a4 -C 1-6 alkylene-, a1, a2, a3 and a4 each represent an integer from 1 to 10; *Ab indicates the binding site with Ab).

9. R st1 The antibody-drug conjugate or salt thereof according to claim 8, wherein is C5 alkylene.

10. The antibody-drug conjugate or a salt thereof according to claim 7, wherein CLL is a partial structure represented by formula (CL-1) that is cleavable in vivo. (In the formula, R AA are each independently H, methyl, isopropyl, isobutyl, sec-butyl, benzyl, p-hydroxybenzyl, hydroxymethyl, 1-hydroxyethyl, -CH2-C(=O)-OH, -(CH2)2-C(=O)-OH, -CH2-C(=O)-NH2, -(CH2)2-C(=O)-NH2, -(CH2)4-NH2, -(CH2)3-NH-C(=NH)-NH2, -(CH2)3-NH-C(=O)-NH2, -CH2-SH or -CH2-S-CH3, or a group selected from the group consisting of the following formulae (RAA-1) and (RAA-2), d is an integer from 1 to 6; *STR indicates the bond to Str).

11. R AA The antibody-drug conjugate or salt thereof of claim 10, wherein each is independently methyl or isopropyl, and d is 2.

12. R AA are, independently from each other, isopropyl or -(CH2)3-NH-C(=O)-NH2, and d is 2. The antibody-drug conjugate or salt thereof of claim 10.

13. R AA The antibody-drug conjugate or salt thereof according to claim 10, wherein each is independently H or benzyl, and d is 4.

14. The antibody-drug conjugate or salt thereof according to claim 7, wherein Sp is a spacer unit represented by the formula (SP-1) and t is 1. (In the formula, R SP , H, C 1-6 Alkyl, -OC 1-6 Alkyl, halogen, or halogenoC 1-6 is alkyl, *CLL indicates the junction with CLL.

15. R SP is H. The antibody-drug conjugate or salt thereof of claim 14 .

16. The antibody-drug conjugate or salt thereof described in claim 7, wherein t is 0.

17. The antibody-drug conjugate or salt thereof according to claim 1, wherein formula (I) is represented by formula (AD-1a) or (AD-2a): where Ab is an antibody or an antigen-binding fragment thereof, A is a CR A or N, R A is H, cyano, or optionally substituted C 1-３ alkyl, Q is CR Q or N, R Q H, halogen, C 3-６ Cycloalkyl, vinyl, or optionally substituted C 1-３ alkyl, E is CH or N, R 1 is cyano, OH, halogen, and optionally substituted C 1-３ naphthyl optionally substituted with one or two groups selected from the group consisting of alkyl, or a group selected from the group consisting of the following formulae (III), (IV) and (V): R 1a , R 1b and R 1c are each independently H, vinyl, halogen, or optionally substituted C 1-３ alkyl, R 3 is optionally substituted C 1-6 alkyl, optionally substituted heterocycloalkyl, or optionally substituted heteroaryl; X is a bond, -CH2-, -O-, -S-, or -NR 4X - and R 4X is H or optionally substituted C 1-３ is alkyl, Y 1 is -O-(optionally substituted C 1-３ Alkylene)- ＊Y2 , -S-(optionally substituted C 1-３ Alkylene)- ＊Y2 , -SO2-(optionally substituted C 1-３ Alkylene)- ＊Y2 , -NR Y -(optionally substituted C 1-３ Alkylene)- ＊Y2 , -(optionally substituted C 1-３ Alkylene)-O- ＊Y2 , -(optionally substituted C 1-３ Alkylene)-S- ＊Y2 , -(optionally substituted C 1-３ Alkylene)-SO2- ＊Y2 or -(optionally substituted C 1-３ (alkylene)-NR Y - ＊Y2 And ( ＊Y2 is Y 2 ), R Y is H or optionally substituted C 1-３ is alkyl, Y 2 is a bond, optionally substituted phenylene or optionally substituted heteroarylene; L P is Y 2 and EUB, wherein EUB is a group capable of binding to an E3 ubiquitin ligase selected from the group consisting of VHL, cereblon, IAP, MDM2, DCAF11, DCAF15, DCAF16, BIRC2, KEAP1, RNF4, RNF114, FEM1B, and AhR, and R st1 is C 1-12 is alkylene, and R AA are each independently H, methyl, isopropyl, benzyl, or -(CH2)3-NH-C(=O)-NH2, d is an integer from 2 to 4, t is 0 or 1, and n is a number from 1 to 20.

18. The antibody-drug conjugate or salt thereof according to claim 1, wherein formula (I) is represented by formula (AD-3a), (AD-4a), (AD-5a), (AD-6a), (AD-7a), (AD-8a), (AD-9a), (AD-10a), (AD-11a), (AD-12a), (AD-13a), or (AD-25a). (In the formula, R st1 is C 1-12 alkylene, R AA are each independently H, methyl, isopropyl, benzyl, or -(CH2)3-NH-C(=O)-NH2, d is an integer from 2 to 4, t is 0 or 1, and n is a number from 1 to 20. Compounds with an "*" in their chemical structure indicate that the compound has a single axial or central chirality. The same applies below.).

19. The antibody-drug conjugate or a salt thereof according to claim 1, wherein formula (I) is represented by formula (AD-14), (AD-15), (AD-16), (AD-17), (AD-18), (AD-19), (AD-20), (AD-21), (AD-22), (AD-23), (AD-24), or (AD-25). (wherein n is a number from 1 to 20).

20. The antibody-drug conjugate or salt thereof according to any one of claims 1 to 19, wherein Ab is cetuximab and n is a number between 2 and 5. twenty one. Ab, 5T4, ADAM9, ALPP, ALPPL2, AXL, B7H3, B7H4, BCMA, CA9, CCR2, CCR7, CD123, CD166, CD19, CD20, CD22, CD25, CD30, CD33, CD37, CD38, CD45, CD46, CD70, CD74, CD79b, CDH3, CDH6, CLDN1, CLDN4, CLDN6, CLDN18.2, cMET, EGFR, EphA3, FAP, FGFR3, Fibronectin, FOLRa, Globo H, GPRC5D, HER2, HER3, IGF1R, Integrin The antibody-drug conjugate or salt thereof according to any one of claims 1 to 19, which is an antibody or antigen-binding fragment that binds to one or more antigens selected from the group consisting of αV, KAAG1, LIV1, MSLN, MT1-MMP, MUC1, MUC4, NaPi2b, Nectin4, PD-L1, PSMA, PTK7, ROR1, ROR2, SEZ6, SialylTn, TF, TROP2, TSPAN8, and VEGF.

22. The antibody-drug conjugate or salt thereof according to any one of claims 1 to 19, wherein Ab is an antibody or antigen-binding fragment that binds to one or more antigens selected from the group consisting of EGFR, HER2, cMET, and TROP2.

23. The antibody-drug conjugate or salt thereof according to any one of claims 1 to 19, wherein Ab is an anti-EGFR antibody or an antigen-binding fragment thereof.

24. The antibody-drug conjugate or salt thereof according to claim 23, wherein Ab is an anti-EGFR antibody or an antigen-binding fragment thereof comprising a heavy chain variable region and a light chain variable region according to the following (1) or (2): (1) a heavy chain variable region comprising a CDR1 consisting of the amino acid sequence from 31 to 35 of SEQ ID NO:1, a CDR2 consisting of the amino acid sequence from 50 to 65 of SEQ ID NO:1, and a CDR3 consisting of the amino acid sequence from 98 to 108 of SEQ ID NO:1, and a light chain variable region comprising a CDR1 consisting of the amino acid sequence from 24 to 34 of SEQ ID NO:2, a CDR2 consisting of the amino acid sequence from 50 to 56 of SEQ ID NO:2, and a CDR3 consisting of the amino acid sequence from 89 to 97 of SEQ ID NO:2; or (2) a heavy chain variable region comprising a CDR1 consisting of the amino acid sequence from 31 to 35 of SEQ ID NO:3, a CDR2 consisting of the amino acid sequence from 50 to 65 of SEQ ID NO:3, and a CDR3 consisting of the amino acid sequence from 98 to 108 of SEQ ID NO:3, and A light chain variable region comprising CDR1 consisting of the amino acid sequence from amino acid numbers 24 to 34 of SEQ ID NO: 4, CDR2 consisting of the amino acid sequence from amino acid numbers 50 to 56 of SEQ ID NO: 4, and CDR3 consisting of the amino acid sequence from amino acid numbers 89 to 97 of SEQ ID NO:

4.

25. The antibody-drug conjugate or salt thereof according to claim 23, wherein Ab is an anti-EGFR antibody or an antigen-binding fragment thereof comprising a heavy chain variable region and a light chain variable region selected from the group consisting of the following (1) to (3): (1) a heavy chain variable region consisting of the amino acid sequence from amino acid number 1 to 119 of SEQ ID NO:1 and a light chain variable region consisting of the amino acid sequence from amino acid number 1 to 107 of SEQ ID NO:2; (2) a heavy chain variable region consisting of the amino acid sequence from amino acid number 1 to 119 of SEQ ID NO:3 and a light chain variable region consisting of the amino acid sequence from amino acid number 1 to 107 of SEQ ID NO:4; and (3) a heavy chain variable region and a light chain variable region having at least 90% or more identity to the heavy chain variable region and light chain variable region according to (1) or (2) above.

26. The antibody-drug conjugate or salt thereof according to claim 23, wherein the Ab is an anti-EGFR antibody of IgG1 or IgG4 type.

27. The antibody-drug conjugate or salt thereof according to claim 23, wherein the Ab is an anti-EGFR antibody consisting of a heavy chain of SEQ ID NO:1 and a light chain of SEQ ID NO:

2.

28. The antibody-drug conjugate or salt thereof according to any one of claims 21 to 23, wherein the Ab is an antibody that has been post-translationally modified or in which any amino acid residue has been substituted with cysteine ​​or a non-natural amino acid.

29. A pharmaceutical composition comprising the antibody-drug conjugate or salt thereof according to any one of claims 1 to 28, and a pharma- ceutically acceptable excipient.

30. The pharmaceutical composition of claim 29 for use in the treatment of cancer.

31. The pharmaceutical composition according to claim 30, wherein the cancer is a blood cancer or a solid cancer.

32. The pharmaceutical composition according to claim 30, wherein the cancer is a cancer expressing G12D mutant KRAS.

33. An antibody-drug conjugate or a salt thereof according to any one of claims 1 to 28 for use in the treatment of cancer.

34. A method for treating cancer, comprising the step of administering to a subject a therapeutically effective amount of the antibody-drug conjugate or salt thereof according to any one of claims 1 to 28.

35. Use of an antibody-drug conjugate or a salt thereof according to any one of claims 1 to 28 in the manufacture of a pharmaceutical composition for the treatment of cancer.

36. A drug-linker conjugate represented by formula (LD-1) or a salt thereof (Wherein, D is a heterocyclic compound having an activity of inducing degradation of G12D mutant KRAS protein, R st1 is C 1-12 CLL is an alkylene; CLL is a moiety that can be cleaved in vivo; Sp is a spacer unit that is bonded to CLL and D; and t is 0 or 1.

37. D is a heterocyclic compound represented by formula (II), A is CR A or N, R A is H, cyano, or optionally substituted C 1-３ alkyl, Q is CR Q or N, R Q H, halogen, C 3-６ Cycloalkyl, vinyl, or optionally substituted C 1-３ alkyl, E is CH or N, R 1 is cyano, OH, halogen, and optionally substituted C 1-３ naphthyl optionally substituted with one or two groups selected from the group consisting of alkyl, or a group selected from the group consisting of the following formulae (III), (IV) and (V): R 1a , R 1b and R 1c are each independently H, vinyl, halogen, or optionally substituted C 1-３ alkyl, R 2 -V １ -V 2 or W, V 1 is a bond, -CH2-, -O-, -S- or -N(R V1 )- and R V1 is H or optionally substituted C 1-３ is alkyl, V 2 is a group selected from the group consisting of the following formulas (VI) and (VII): W is a group selected from the group consisting of the following formulas (VIII), (IX), (X), (XI), (XII), (XIII), (XIV), (XV) and (XVI), R 2a are each independently OH, OCH3, F or optionally substituted C 1-３ alkyl, 2a is bonded only to a carbon atom that is a constituent atom of a ring selected from the group consisting of an azetidine ring represented by formula (VI), a pyrrolidine ring represented by formula (VII), a piperidine ring represented by formula (VIII), and a piperazine ring represented by formula (IX), m is an integer of 0 to 2, R 3 is optionally substituted C 1-6 alkyl, optionally substituted heterocycloalkyl, or optionally substituted heteroaryl; X is a bond, -CH2-, -O-, -S-, or -NR 4X - and R 4X is H or optionally substituted C 1-３ is alkyl, Y 1 is -O-(optionally substituted C 1-３ Alkylene)- ＊Y2 , -S-(optionally substituted C 1-３ Alkylene)- ＊Y2 , -SO2-(optionally substituted C 1-３ Alkylene)- ＊Y2 , -NR Y -(optionally substituted C 1-３ Alkylene)- ＊Y2 , -(optionally substituted C 1-３ Alkylene)-O- ＊Y2 , -(optionally substituted C 1-３ Alkylene)-S- ＊Y2 , -(optionally substituted C 1-３ Alkylene)-SO2- ＊Y2 or -(optionally substituted C 1-３ (alkylene)-NR Y - ＊Y2 And ( ＊Y2 is Y 2 ), R Y is H or optionally substituted C 1-３ is alkyl, Y 2 is a bond, optionally substituted phenylene or optionally substituted heteroarylene; L P is Y 2 and EUB, wherein EUB is a group capable of binding to one E3 ubiquitin ligase selected from the group consisting of VHL, cereblon, IAP, MDM2, DCAF11, DCAF15, DCAF16, BIRC2, KEAP1, RNF4, RNF114, FEM1B and AhR, and Sp is a spacer unit and binds to CLL and D, wherein Sp binds to any nitrogen atom of -NH- or oxygen atom of -OH contained in D. The drug-linker conjugate or salt thereof of claim 36.

38. V 2 is a group selected from the group consisting of the following formula (VIb) and formula (VIIb): *SP indicates the bond with Sp.) W is a group selected from the group consisting of the following formulas (VIIIb), (IXb), (Xb), (XIb), (XIIb), (XIIIb), (XIVb), (XVb) and (XVIb): *SP indicates the bond with Sp.) Sp is a spacer unit and binds to CLL and D, where Sp is V 2 or a nitrogen atom contained in W ＊SP The drug-linker conjugate or salt thereof of claim 37, which is bound to D at a bond represented by the following formula:

39. A is N and Q is CR Q and R Q is cyclopropyl, E is CH, and R 1 is represented by the following formula (III-2), R 2 But -V 1 -V 2 or W, V 1 is -N(CH3)-, V 2 is represented by the following formula (VII-2), W is represented by the following formula (XIV): R 3 is n-propyl optionally substituted with -OCH3, or tetrahydropyranyl; X is -O-; Y 1 But -O-(methylene)- ＊Y2 And ( ＊Y2 is Y 2 ), Y 2 is phenylene, L P But, Y 2 and EUB is a group capable of binding to an E3 ubiquitin ligase selected from the group consisting of VHL and cereblon.

40. V 2 is represented by the following formula (VII-2b) ( *SP indicates the bond with Sp.) W is represented by the following formula (XIVb): *SP indicates the bond with Sp.) Sp is a spacer unit and binds to CLL and D, where Sp is V 2 or a nitrogen atom contained in W ＊SP The drug-linker conjugate or salt thereof of claim 39, which is bound to D at a bond represented by the following formula:

41. D is (4R)-1-[(2S)-2-(4-{4-[({6-cyclopropyl-4-[(1S,4S)-2,5-diazabicyclo[2.2.1]heptan-2-yl]-7-(6-fluoro-5-methyl-1H-indazol-4-yl)-2-[(oxan-4-yl)oxy]quinazolin-8-yl}oxy)methyl]phenyl}-1H-1,2,3-triazol-1-yl)-3-methylbutanoyl]-4-hydroxy-N-{(1R)-2-hydroxy-1-[4-(4-methyl-1,3-thiazol-5-yl)phenyl]ethyl}-L-prolinamide; (4R)-1-[(2S)-2-(4-{4-[({6-cyclopropyl-4-[(1S,4S)-2,5-diazabicyclo[2.2.1]heptan-2-yl]-7-(6-fluoro-5-methyl-1H-indazol-4-yl)-2-[(oxan-4-yl)oxy]quinazolin-8-yl}oxy)methyl]phenyl}-1H-1,2,3-triazol-1-yl)-3-methylbutanoyl]-4-hydroxy-N-{(1R)-2-hydroxy-1-[4-(2-oxo-1,3-oxazolidin-3-yl)phenyl]ethyl}-L-prolinamide, (4R)-1-[(2S)-2-(4-{4-[({6-cyclopropyl-4-[(1S,4S)-2,5-diazabicyclo[2.2.1]heptan-2-yl]-7-(6-fluoro-5-methyl-1H-indazol-4-yl)-2-[(oxan-4-yl)oxy]quinazolin-8-yl}oxy)methyl]phenyl}-1H-1,2,3-triazol-1-yl)-3-methylbutanoyl]-4-hydroxy-N-{(1R)-2-hydroxy-1-[4-(1-methyl-1H-pyrazol-5-yl)phenyl]ethyl}-L-prolinamide, (4R)-1-[(2S)-2-(4-{4-[({6-cyclopropyl-4-[(1S,4S)-2,5-diazabicyclo[2.2.1]heptan-2-yl]-7-(6-fluoro-5-methyl-1H-indazol-4-yl)-2-[(2S)-2-methoxypropoxy]quinazolin-8-yl}oxy)methyl]phenyl}-1H-1,2,3-triazol-1-yl)-3-methylbutanoyl]-4-hydroxy-N-{(1R)-2-hydroxy-1-[4-(4-methyl-1,3-thiazol-5-yl)phenyl]ethyl}-L-prolinamide, (4R)-1-[(2S)-2-(4-{4-[({6-cyclopropyl-4-[(1S,4S)-2,5-diazabicyclo[2.2.1]heptan-2-yl]-7-(6-fluoro-5-methyl-1H-indazol-4-yl)-2-[(2S)-2-methoxypropoxy]quinazolin-8-yl}oxy)methyl]phenyl}-1H-1,2,3-triazol-1-yl)-3-methylbutanoyl]-N-{(1R)-1-[4-(1-ethyl-1H-pyrazol-5-yl)phenyl]-2-hydroxyethyl}-4-hydroxy-L-prolinamide, (4R)-1-[(2S)-2-(4-{4-[({6-cyclopropyl-4-[(1S,4S)-2,5-diazabicyclo[2.2.1]heptan-2-yl]-7-(6-fluoro-5-methyl-1H-indazol-4-yl)-2-[(2S)-2-methoxypropoxy]quinazolin-8-yl}oxy)methyl]phenyl}-1H-1,2,3-triazol-1-yl)-3-methylbutanoyl]-4-hydroxy-N-{(1R)-2-hydroxy-1-[4-(4-methyl-1,3-oxazol-5-yl)phenyl]ethyl}-L-prolinamide, (4R)-1-[(2S)-2-{4-[4-({[(7M)-6-cyclopropyl-7-(6-fluoro-5-methyl-1H-indazol-4-yl)-2-[(2S)-2-methoxypropoxy]-4-{methyl[(3S)-pyrrolidin-3-yl]amino}quinazolin-8-yl]oxy}methyl)phenyl]-1H-1,2,3-triazol-1-yl}-3-methylbutanoyl]-4-hydroxy-N-{(1R)-2-hydroxy-1-[4-(4-methyl-1,3-thiazol-5-yl)phenyl]ethyl}-L-prolinamide, (4R)-1-[(2S)-2-{4-[4-({[(7M)-6-cyclopropyl-7-(6-fluoro-5-methyl-1H-indazol-4-yl)-2-[(2S)-2-methoxypropoxy]-4-{methyl[(3S)-pyrrolidin-3-yl]amino}quinazolin-8-yl]oxy}methyl)phenyl]-1H-1,2,3-triazol-1-yl}-3-methylbutanoyl]-N-{(1R)-1-[4-(1-ethyl-1H-pyrazol-5-yl)phenyl]-2-hydroxyethyl}-4-hydroxy-L-prolinamide, 3-(5-{[(3S)-4-{4-[({(7M)-6-cyclopropyl-4-[(1S,4S)-2,5-diazabicyclo[2.2.1]heptan-2-yl]-7-(6-fluoro-5-methyl-1H-indazol-4-yl)-2-[(oxan-4-yl)oxy]quinazolin-8-yl}oxy)methyl]benzoyl}-3-methylpiperazin-1-yl]methyl}-3-methyl-2-oxo-2,3-dihydro-1H-benzimidazol-1-yl)piperidine-2,6-dione, 1-(6-{[(3S)-4-{4-[({(7M)-6-cyclopropyl-4-[(1S,4S)-2,5-diazabicyclo[2.2.1]heptan-2-yl]-7-(6-fluoro-5-methyl-1H-indazol-4-yl)-2-[(oxan-4-yl)oxy]quinazolin-8-yl}oxy)methyl]benzoyl}-3-methylpiperazin-1-yl]methyl}-1-methyl-1H-indazol-3-yl)-1,3-diazinan-2,4-dione, 3-(5-{[(3S)-4-{4-[({(7M)-6-cyclopropyl-4-[(1S,4S)-2,5-diazabicyclo[2.2.1]heptan-2-yl]-7-(6-fluoro-5-methyl-1H-indazol-4-yl)-2-[(2S)-2-methoxypropoxy]quinazolin-8-yl}oxy)methyl]benzoyl}-3-methylpiperazin-1-yl]methyl}-3-methyl-2-oxo-2,3-dihydro-1H-benzimidazol-1-yl)piperidine-2,6-dione, or 38. The drug-linker conjugate or salt thereof according to claim 36 or 37, wherein phosphate=dihydrogen=(2R)-2-({(4R)-1-[(2S)-2-{4-[4-({[(7M)-6-cyclopropyl-7-(6-fluoro-5-methyl-1H-indazol-4-yl)-2-[(2S)-2-methoxypropoxy]-4-{methyl[(3S)-pyrrolidin-3-yl]amino}quinazolin-8-yl]oxy}methyl)phenyl]-1H-1,2,3-triazol-1-yl}-3-methylbutanoyl]-4-hydroxy-L-prolyl}amino)-2-[4-(1H-1,2,4-triazol-1-yl)phenyl]ethyl.

42. The drug-linker conjugate or salt thereof according to claim 36, wherein formula (LD-1) is represented by formula (LD-2a) or (LD-3a): (Wherein, A is CR A or N, R A is H, cyano, or optionally substituted C 1-３ alkyl, Q is CR Q or N, R Q H, halogen, C 3-６ Cycloalkyl, vinyl, or optionally substituted C 1-３ alkyl, E is CH or N, R 1 is cyano, OH, halogen, and optionally substituted C 1-３ naphthyl optionally substituted with one or two groups selected from the group consisting of alkyl, or a group selected from the group consisting of the following formulae (III), (IV) and (V): R 1a , R 1b and R 1c are each independently H, vinyl, halogen, or optionally substituted C 1-３ alkyl, R 3 is optionally substituted C 1-6 alkyl, optionally substituted heterocycloalkyl, or optionally substituted heteroaryl; X is a bond, -CH2-, -O-, -S-, or -NR 4X - and R 4X is H or optionally substituted C 1-３ is alkyl, Y 1 is -O-(optionally substituted C 1-３ Alkylene)- ＊Y2 , -S-(optionally substituted C 1-３ Alkylene)- ＊Y2 , -SO2-(optionally substituted C 1-３ Alkylene)- ＊Y2 , -NR Y -(optionally substituted C 1-３ Alkylene)- ＊Y2 , -(optionally substituted C 1-３ Alkylene)-O- ＊Y2 , -(optionally substituted C 1-３ Alkylene)-S- ＊Y2 , -(optionally substituted C 1-３ Alkylene)-SO2- ＊Y2 or -(optionally substituted C 1-３ (alkylene)-NR Y - ＊Y2 And ( ＊Y2 is Y 2 ), R Y is H or optionally substituted C 1-３ is alkyl, Y 2 is a bond, optionally substituted phenylene or optionally substituted heteroarylene; L P is Y 2 and EUB, wherein EUB is a group capable of binding to an E3 ubiquitin ligase selected from the group consisting of VHL and cereblon; R st1 is C 1-12 is alkylene, and R AA are each independently H, methyl, isopropyl, benzyl, or -(CH2)3-NH-C(=O)-NH2, d is an integer from 2 to 4, and t is 0 or 1.

43. The drug-linker conjugate or salt thereof according to claim 36, wherein formula (LD-1) is represented by formula (LD-4a), (LD-5a), (LD-6a), (LD-7a), (LD-8a), (LD-9a), (LD-10a), (LD-11a), (LD-12a), (LD-13a), (LD-14a), or (LD-26a). (In the formula, R st1 is C 1-12 alkylene, R AA are each independently H, methyl, isopropyl, benzyl, or -(CH2)3-NH-C(=O)-NH2, d is an integer from 2 to 4, and t is 0 or 1.

44. The drug-linker conjugate or salt thereof described in claim 36, wherein formula (LD-1) is represented by formula (LD-15), (LD-16), (LD-17), (LD-18), (LD-19), (LD-20), (LD-21), (LD-22), (LD-23), (LD-24), (LD-25), or (LD-26).