A pharmaceutical combination of a parp7 inhibitor combination and its use for treating tumors

Abstract

This application relates to a combination of PARP7 inhibitors and its use in the treatment of tumors, the combination comprising: a first active ingredient, a PARP7 inhibitor; a second active ingredient, a CTLA-4 inhibitor or a platinum complex; and optionally a third active ingredient, a PD-1 inhibitor or a PD-L1 inhibitor.

Description

A drug combination of PARP7 inhibitors and its use in treating tumors Technical Field

[0001] The present application belongs to the field of medical technology and relates to a drug combination that can be used for anti-tumor treatment. Specifically, the present application relates to a drug combination of a PARP7 inhibitor and its use in treating tumors. Background Art

[0002] 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD)-inducible poly(ADP-ribose) polymerase (PARP7) is a member of the MonoPARP family. TCDD activates the aryl hydrocarbon receptor (AHR) to upregulate its expression. PARP7 interacts with the kinase TBK1 and ADP-ribosylates it, leading to inhibition of TBK1 activity and downregulation of IFN-I (type I interferon) responses, thereby suppressing the body's antiviral and tumor immune responses. As a negative regulator of nucleic acid sensing in tumor cells, inhibition of PARP7 has been shown to restore the IFN-I signaling pathway's response to nucleic acids in tumor models. This restoration of signaling can directly inhibit cell proliferation and activate the immune system, both of which contribute to tumor regression.

[0003] CTLA-4, or cytotoxic T-lymphocyte-associated protein 4 (also known as CD152), is a transmembrane protein on the surface of T cells, encoded by the CTLA-4 gene. CTLA-4 shares up to 70% homology with CD28, and both bind to the same ligand, the B7 molecule (CD80 and CD86). CD28 is a co-stimulatory immune checkpoint responsible for transmitting activation signals to T cells, promoting their differentiation and proliferation into effector cells; CTLA-4, on the other hand, is a co-inhibitory immune checkpoint responsible for transmitting inhibitory signals to T cells, suppressing their activity. Due to its higher affinity for the B7 molecule, CTLA-4 competes with and blocks CD28's activation of T cells, thereby inhibiting T cell proliferation and activation. CTLA-4 inhibitors work by blocking CTLA-4, thereby reactivating T cell differentiation and proliferation into effector cells, which then infiltrate tumor tissue and ultimately kill tumor cells. Clinical applications have shown that CTLA-4 inhibitors have limited efficacy. Monotherapy has shown limited efficacy in only a few tumors, such as melanoma, but patients with most tumor types rarely benefit from them. Furthermore, they have significant side effects. This is because CTLA-4 inhibitors activate the immune system to eliminate tumor tissue, which inevitably leads to overactivation of the immune system, resulting in immune-related side effects such as diarrhea and rash. Therefore, new and improved therapies are urgently needed to enhance the therapeutic effects of existing therapies and reduce side effects.

[0004] Platinum complexes are cell cycle-nonspecific drugs and are more broadly classified as alkylating cytotoxic drugs. They primarily interact with DNA within tumor cells to form Pt-DNA adducts, which hinder normal DNA replication and transcription. Although different platinum complexes differ slightly in the manner and site of DNA binding, their mechanism of action is essentially the same. Platinum complexes were first discovered as chemotherapy drugs in the 1960s and are one of the most important anticancer drugs in clinical practice. However, platinum complexes, represented by cisplatin, have severe toxicity, and drug resistance caused by reduced platinum uptake, increased efflux, drug inactivation, and DNA damage repair also limits their application. Therefore, new and improved therapies are urgently needed to enhance the therapeutic efficacy of existing therapies, reduce side effects, and overcome drug resistance.

[0005] Programmed death 1 protein (PD-1, Pdcd-1, or CD279) is a 55KD receptor protein related to the CD28 / CTLA4 costimulatory / inhibitory receptor family. Cancer cells express PD-1's ligand, PD-L1, which allows them to evade the host immune system. Marketed PD-1 inhibitors can significantly prolong overall survival by interfering with tumor immunosuppression mechanisms. However, this treatment approach only elicits responses in a subset of patients, or some patients may experience a favorable initial response, only to experience decreased or absent efficacy over time. Therefore, new and improved therapies are urgently needed to enhance the therapeutic effects of existing therapies.

[0006] Summary of the Invention

[0007] The applicant unexpectedly discovered in the study that the combination therapy of PARP7 inhibitors and CTLA-4 inhibitors, the combination therapy of PARP7 inhibitors, CTLA-4 inhibitors and PD-1 inhibitors or PD-L1 inhibitors, the combination therapy of PARP7 inhibitors and platinum complexes, or the combination therapy of PARP7 inhibitors, platinum complexes and PD-1 inhibitors or PD-L1 inhibitors, all have better efficacy, higher safety and lower drug resistance than their respective monotherapy in preclinical and clinical studies.

[0008] Therefore, the present invention provides a drug combination of a PARP7 inhibitor and its use in treating tumors.

[0009] One or more embodiments of the present invention provide a drug combination comprising: a first active ingredient, a PARP7 inhibitor; a second active ingredient, a CTLA-4 inhibitor or a platinum complex; and optionally a third active ingredient, a PD-1 inhibitor or a PD-L1 inhibitor.

[0010] In one or more embodiments of the present invention, the drug combination comprises: (a) a PARP7 inhibitor, (b) a CTLA-4 inhibitor, and optionally (c) a PD-1 inhibitor or a PD-L1 inhibitor.

[0011] In one or more embodiments of the present invention, the drug combination comprises: (a) a PARP7 inhibitor, and (b) a CTLA-4 inhibitor.

[0012] In one or more embodiments of the present invention, the drug combination comprises: (a) a PARP7 inhibitor, (b) a platinum complex, and optionally (c) a PD-1 inhibitor or a PD-L1 inhibitor.

[0013] In one or more embodiments of the present invention, the drug combination comprises: (a) a PARP7 inhibitor, and (b) a platinum complex.

[0014] In one or more embodiments of the present invention, the PARP7 inhibitor included in the drug combination is selected from RBN-2397, ONO-7119, QLS1103, JAB-26766, NSP-5020, NSP-5033, EB400, or a compound of formula (I) or a pharmaceutically acceptable salt, stereoisomer or deuterated substance thereof:

[0015] in:

[0016] X1 is NH, O or a 4- to 6-membered heterocyclic ring containing 1 to 3 heteroatoms selected from N and O;

[0017] X2 is O or a single bond;

[0018] X3 and X4 are each independently C or N;

[0019] R 1a 、R 1b Each independently is H, D or C 1-6 Alkyl; or R 1a 、R 1b Together with the carbon atom to which it is attached, it forms a 3- to 5-membered cycloalkyl group;

[0020] R 2a 、R 2b Each independently is H, D or C 1-6 Alkyl; or R 2a 、R 2b Together with the carbon atom to which it is attached, it forms a 3- to 5-membered cycloalkyl group;

[0021] R3 is H, D, C 1-6 Alkyl, halogen or cyano, the C 1-6 The alkyl group is optionally substituted with 1 to 3 halogens;

[0022] R4 and R5 are each independently H, D or C 1-6 Alkyl; or R4, R5 and the connected carbon atom form a 3 to 5-membered cycloalkyl;

[0023] R6 and R7 are each independently H, D or C 1-6 Alkyl; or R6, R7 and the connected carbon atom form C=O;

[0024] R8 and R9 are each independently H, D or C 1-6 Alkyl; or R8, R9 and the carbon atom to which they are connected form C=O; or R8 and R9 and the carbon atom to which they are connected form a 3- to 5-membered cycloalkyl;

[0025] R 10 Each independently is C 1-6 Alkyl, C 1-6 Alkoxy, CONR 10a R 10b , halogen, cyano, S(O)2R 10c SR 10d or a 3 to 5-membered cycloalkyl group, the C 1-6 Alkyl, C 1-6 Alkoxy is optionally substituted with 1 to 3 halogens;

[0026] R 10a 、R 10b 、R 10c 、R 10d Each independently is H, D or C 1-6 alkyl;

[0027] A is R a C 1-6 Alkyl, C 3-5 Cycloalkyl, halogen or cyano, the C 1-6 The alkyl group is optionally substituted with 1 to 3 halogens;

[0028] B is a 5- to 10-membered carbocyclic or heterocyclic ring containing 1 to 3 heteroatoms selected from N, O and S;

[0029] C is a 5- to 6-membered heterocyclic ring containing 1 to 3 N heteroatoms;

[0030] m is 1, 2, or 3;

[0031] n is 0, 1, 2, or 3;

[0032] p is 0, 1, 2 or 3.

[0033] In one or more embodiments of the present invention, the PARP7 inhibitor included in the drug combination is selected from RBN-2397, ONO-7119, QLS1103, JAB-26766, NSP-5020, NSP-5033, EB400, or a compound of formula (I) or a pharmaceutically acceptable salt, stereoisomer or deuterated substance thereof, wherein:

[0034] X1 is NH, O or a 4- to 6-membered heterocyclic ring containing 1 to 3 heteroatoms selected from N and O;

[0035] X2 is O or a single bond;

[0036] X3 and X4 are each independently C or N;

[0037] R 1a 、R 1b Each independently is H, D or C 1-6 alkyl;

[0038] R 2a 、R 2b Each independently is H, D or C 1-6 Alkyl; or R 2a 、R 2b Together with the carbon atom to which it is attached, it forms a 3- to 5-membered cycloalkyl group;

[0039] R3 is H, D, C 1-6 Alkyl, halogen or cyano, the C 1-6 The alkyl group is optionally substituted with 1 to 3 halogens;

[0040] R4 and R5 are each independently H, D or C 1-6 Alkyl; or R4, R5 and the connected carbon atom form a 3 to 5-membered cycloalkyl;

[0041] R6 and R7 are each independently H, D or C 1-6 alkyl;

[0042] R8 and R9 are each independently H, D or C 1-6 Alkyl; or R8, R9 and the connected carbon atom form C=O;

[0043] R 10 Each independently is C 1-6 Alkyl, C 1-6 Alkoxy, CONR 10a R 10b , halogen, cyano, S(O)2R 10c SR 10d or a 3 to 5-membered cycloalkyl group, the C 1-6 Alkyl, C 1-6 Alkoxy is optionally substituted with 1 to 3 halogens;

[0044] R 10a 、R 10b 、R 10c 、R 10d Each independently is H, D or C 1-6 alkyl;

[0045] A is R a C 1-6 Alkyl, C 3-5 Cycloalkyl, halogen or cyano, the C 1-6 The alkyl group is optionally substituted with 1 to 3 halogens;

[0046] B is a 5- to 6-membered carbocyclic or heterocyclic ring containing 1 to 3 heteroatoms selected from N, O and S;

[0047] C is a 5- to 6-membered heterocyclic ring containing 1 to 3 N heteroatoms;

[0048] m is 1, 2, or 3;

[0049] n is 0, 1, 2, or 3;

[0050] p is 0, 1, 2 or 3.

[0051] In one or more embodiments of the present invention, the PARP7 inhibitor included in the drug combination is selected from RBN-2397, ONO-7119, QLS1103, JAB-26766, NSP-5020, NSP-5033, EB400 or a compound represented by formula (I-1) or a pharmaceutically acceptable salt, stereoisomer or deuterated substance thereof.

[0052] in:

[0053] X1 is NH or a 4- to 6-membered heterocyclic ring containing 1 to 3 heteroatoms selected from N and O;

[0054] X2 is 0;

[0055] X3 and X4 are each independently C or N;

[0056] R 1a 、R 1b Each independently is H, D or C 1-6 alkyl;

[0057] R 2a 、R 2b Each independently is H, D or C 1-6 alkyl;

[0058] R3 is H, D, C1-6 Alkyl or halogen, the C 1-6 The alkyl group is optionally substituted with 1 to 3 halogens;

[0059] R4 and R5 are each independently H, D or C 1-6 alkyl;

[0060] R6 and R7 are each independently H, D or C 1-6 alkyl;

[0061] R8 and R9 are each independently H, D or C 1-6 Alkyl; or R8 and R9 form C=O with the carbon atom to which they are connected;

[0062] R 10 C 1-6 Alkyl, C 1-6 Alkoxy, cyano or SR 10d , the C 1-6 Alkyl, C 1-6 Alkoxy is optionally substituted with 1 to 3 halogens;

[0063] R 10d H, D or C 1-6 alkyl;

[0064] A is

[0065] B is a 5- to 6-membered carbocyclic or heterocyclic ring containing 1 to 3 heteroatoms selected from N, O and S;

[0066] C is a 5- to 6-membered heterocyclic ring containing 1 to 3 N heteroatoms;

[0067] m is 1, 2, or 3;

[0068] n is 0, 1, 2 or 3.

[0069] In one or more embodiments of the present invention, the PARP7 inhibitor included in the drug combination is selected from RBN-2397, ONO-7119, QLS1103, JAB-26766, NSP-5020, NSP-5033, EB400 or a compound represented by formula (I-2) or a pharmaceutically acceptable salt, stereoisomer or deuterated substance thereof.

[0070] in:

[0071] X1 is NH;

[0072] X2 is 0;

[0073] R 1a 、R 1bEach independently is H, D or C 1-6 alkyl;

[0074] R 2a 、R 2b Each independently is H, D or C 1-6 alkyl;

[0075] R3 is H, D, C 1-6 Alkyl or halogen, the C 1-6 The alkyl group is optionally substituted with 1 to 3 halogens;

[0076] R4 and R5 are each independently H, D or C 1-6 alkyl;

[0077] R6 and R7 are each independently H, D or C 1-6 alkyl;

[0078] R8 and R9 are each independently H, D or C 1-6 Alkyl; or R8 and R9 and the carbon atom to which they are attached form C=O;

[0079] R 10 C 1-6 Alkyl, C 1-6 Alkoxy, cyano or SR 10d , the C 1-6 Alkyl, C 1-6 Alkoxy is optionally substituted with 1 to 3 halogens;

[0080] R 10d H, D or C 1-6 alkyl;

[0081] A is

[0082] B is a 5- to 6-membered carbocyclic or heterocyclic ring containing 1 to 3 heteroatoms selected from N, O and S;

[0083] m is 1, 2, or 3;

[0084] n is 0, 1, 2 or 3.

[0085] In one or more embodiments of the present invention, the PARP7 inhibitor included in the drug combination is selected from RBN-2397, ONO-7119, QLS1103, JAB-26766, NSP-5020, NSP-5033, EB400, or a compound represented by formula (I-2) or a pharmaceutically acceptable salt, stereoisomer, or deuterated form thereof, wherein:

[0086] X1 is NH;

[0087] X2 is 0;

[0088] R 1a 、R 1b Each independently is H, D or C 1-6 alkyl;

[0089] R 2a 、R 2b Each independently is H, D or C 1-6 alkyl;

[0090] R3 is H, D, C 1-6 Alkyl or halogen, the C 1-6 The alkyl group is optionally substituted with 1 to 3 halogens;

[0091] R4 and R5 are each independently H, D or C 1-6 alkyl;

[0092] R6 and R7 are each independently H, D or C 1-6 alkyl;

[0093] R8 and R9 are each independently H, D or C 1-6 Alkyl, or R8 and R9 form C=O with the carbon atom to which they are connected;

[0094] R 10 C 1-6 Alkyl, cyano, or SR 10d , the C 1-6 The alkyl group is optionally substituted with 1 to 3 halogens;

[0095] R 10d H, D or C 1-6 alkyl;

[0096] A is

[0097] B is a 5- to 6-membered carbocyclic or heterocyclic ring containing 1 to 3 heteroatoms selected from N, O and S;

[0098] m is 1, 2, or 3;

[0099] n is 0, 1, 2 or 3.

[0100] In one or more embodiments of the present invention, the PARP7 inhibitor included in the drug combination is selected from RBN-2397, ONO-7119, QLS1103, JAB-26766, NSP-5020, NSP-5033, EB400, or a compound represented by formula (I-2) or a pharmaceutically acceptable salt, stereoisomer, or deuterated form thereof, wherein:

[0101] X1 is selected from NH;

[0102] X2 is selected from O;

[0103] R 1a 、R 1b Each independently selected from H, D or C 1-6 alkyl;

[0104] R 2a 、R 2b Each independently selected from H, D or C 1-6 alkyl;

[0105] R3 is H, D, C 1-6 Alkyl or halogen, the C 1-6 The alkyl group is optionally substituted with 1 to 3 halogens;

[0106] R4 and R5 are each independently H or D;

[0107] R6 and R7 are each independently H or D;

[0108] R8 and R9 are each independently H or D;

[0109] R 10 CF3 or SR 10d ;

[0110] R 10d H, D or C 1-6 alkyl;

[0111] A is

[0112] B is

[0113] m is 1, 2, or 3;

[0114] n is 0, 1, 2 or 3.

[0115] In one or more embodiments of the present invention, the PARP7 inhibitor included in the drug combination is selected from RBN-2397, ONO-7119, QLS1103, JAB-26766, NSP-5020, NSP-5033, EB400, or a compound represented by formula (I-2) or a pharmaceutically acceptable salt, stereoisomer, or deuterated form thereof, wherein:

[0116] X1 is selected from NH;

[0117] X2 is selected from O;

[0118] R 1a 、R 1b Each independently selected from H, D or C 1-3 alkyl;

[0119] R 2a 、R2b Each independently selected from H, D or C 1-3 alkyl;

[0120] R3 is selected from H, D or CF3;

[0121] R4 and R5 are each independently selected from H or D;

[0122] R6 and R7 are each independently selected from H or D;

[0123] R8 and R9 are each independently selected from H or D;

[0124] R 10 is CF3;

[0125] A is

[0126] B is

[0127] m is 1, 2, or 3;

[0128] n is 0, 1 or 2.

[0129] In one or more embodiments of the present invention, the PARP7 inhibitor included in the drug combination is selected from RBN-2397, ONO-7119, QLS1103, JAB-26766, NSP-5020, NSP-5033, EB400 or a compound represented by formula (I-3) or a pharmaceutically acceptable salt, stereoisomer or deuterated substance thereof.

[0130] in:

[0131] X1 is NH or a 4- to 6-membered heterocyclic ring containing 1 to 3 heteroatoms selected from N and O;

[0132] X2 is 0;

[0133] R 1a 、R 1b Each independently is H, D or C 1-6 alkyl;

[0134] R 2a 、R 2b Each independently is H, D or C 1-6 alkyl;

[0135] R4 and R5 are each independently H, D or C 1-6 alkyl;

[0136] R6 and R7 are each independently H, D or C 1-6 alkyl;

[0137] R8 and R9 are each independently H, D or C 1-6 Alkyl; or R8, R9 and the connected carbon atom form C=O;

[0138] R 10 C 1-6 Alkyl, C 1-6 Alkoxy, cyano or SR 10d , the C 1-6 Alkyl, C 1-6 Alkoxy is optionally substituted with 1 to 3 halogens;

[0139] R 10d H, D or C 1-6 alkyl;

[0140] A is

[0141] B is a 5- to 6-membered carbocyclic or heterocyclic ring containing 1 to 3 heteroatoms selected from N, O and S;

[0142] m is 1, 2, or 3;

[0143] n is 0, 1, 2 or 3.

[0144] In one or more embodiments of the present invention, the PARP7 inhibitor included in the drug combination is selected from RBN-2397, ONO-7119, QLS1103, JAB-26766, NSP-5020, NSP-5033, EB400, or a compound represented by formula (I-3) or a pharmaceutically acceptable salt, stereoisomer or deuterated substance thereof, wherein:

[0145] X1 is NH or a 4- to 6-membered heterocyclic ring containing 1 to 3 heteroatoms selected from N and O;

[0146] X2 is 0;

[0147] R 1a 、R 1b Each independently is H, D or C 1-3 alkyl;

[0148] R 2a 、R 2b Each independently is H, D or C 1-3 alkyl;

[0149] R4 and R5 are each independently H, D or C 1-3 alkyl;

[0150] R6 and R7 are each independently H, D or C 1-3 alkyl;

[0151] R8 and R9 are each independently H, D or C 1-3 Alkyl; or R8 and R9 form C=O with the carbon atom to which they are connected;

[0152] R 10 C 1-6 Alkyl, cyano or SR 10d , the C 1-6 The alkyl group is optionally substituted with 1 to 3 halogens;

[0153] R 10d H, D or C 1-6 alkyl;

[0154] A is

[0155] B is

[0156] m is 1, 2, or 3;

[0157] n is 0, 1 or 2.

[0158] In one or more embodiments of the present invention, the PARP7 inhibitor included in the drug combination is selected from RBN-2397, ONO-7119, QLS1103, JAB-26766, NSP-5020, NSP-5033, EB400, or a compound represented by formula (I-3) or a pharmaceutically acceptable salt, stereoisomer or deuterated substance thereof, wherein:

[0159] X1 is NH;

[0160] X2 is 0;

[0161] R 1a 、R 1b Each independently is H, D or C 1-3 alkyl;

[0162] R 2a 、R 2b Each independently is H or D;

[0163] R4 and R5 are each independently H or D;

[0164] R6 and R7 are each independently H or D;

[0165] R8 and R9 are each independently H or D;

[0166] R 10 is CF3;

[0167] A is

[0168] B is

[0169] m is 1, 2, or 3;

[0170] n is 0, 1 or 2.

[0171] In one or more embodiments of the present invention, the PARP7 inhibitor included in the drug combination is selected from RBN-2397, ONO-7119, QLS1103, JAB-26766, NSP-5020, NSP-5033, EB400, or the following compounds or pharmaceutically acceptable salts, stereoisomers or deuterated derivatives thereof:

[0172] In one or more embodiments of the present invention, the CTLA-4 inhibitor included in the drug combination is selected from one or a combination of antibodies, small molecule compounds, microRNA, siRNA, and shRNA.

[0173] In one or more embodiments of the present invention, the CTLA-4 inhibitor included in the drug combination is selected from one or a combination of antibodies, small molecule compounds, microRNA, siRNA, and shRNA having CTLA-4 inhibitory activity.

[0174] In one or more embodiments of the present invention, the CTLA-4 inhibitor antibody included in the drug combination is selected from one or more combinations of ipilimumab, tremelimumab, gotistobart, SHR-8068, ADG-126, ADG-116, YH-001, XTX-101, BMS-986218, porustobart, botensilimab, BA-3071, KD-6001, Zaliferelimab, Quavonlimab, REGN-4659, IMM-27M, MT-8421, BCD-145, and KN-044.

[0175] In one or more embodiments of the present invention, the platinum complex included in the drug combination is selected from one or a combination of cisplatin, carboplatin, cyclothiaplatin, nedaplatin, oxaliplatin, and lobaplatin.

[0176] In one or more embodiments of the present invention, the PD-1 inhibitor or PD-L1 inhibitor included in the drug combination is selected from Pembrolizumab, Nivolumab, Serplulimab, Pidilizumab, Lambrolizumab, Atezolizumab, Toripalimab, Sintilimab, Tislelizumab, Camrelizumab, Penpulimab, Zimberelimab, Envafolimab, sugemalimab, dostarlimab, cadonilimab, cemiplimab, retifanlimab, BMS-986213, HX-008, geptanolimab, prolgolimab, socazolimab, avelumab, adebrelimab, or durvalumab.

[0177] In one or more embodiments of the present invention, in the drug combination, the PARP7 inhibitor, the CTLA-4 inhibitor and the optional PD-1 inhibitor or PD-L1 inhibitor are present in the same pharmaceutical composition, or the PARP7 inhibitor, the CTLA-4 inhibitor and the optional PD-1 inhibitor or PD-L1 inhibitor are present in different pharmaceutical compositions.

[0178] In one or more embodiments of the present invention, the pharmaceutical combination comprises:

[0179] (i) a first pharmaceutical composition comprising a PARP7 inhibitor, a pharmaceutically acceptable carrier and / or excipient;

[0180] (ii) a second pharmaceutical composition comprising a CTLA-4 inhibitor, a pharmaceutically acceptable carrier and / or excipient; and

[0181] Optional (iii) a third pharmaceutical composition comprising a PD-1 inhibitor or a PD-L1 inhibitor, a pharmaceutically acceptable carrier and / or excipient.

[0182] Alternatively, the drug combination comprises:

[0183] A single pharmaceutical composition comprising a PARP7 inhibitor, a CTLA-4 inhibitor, optionally a PD-1 inhibitor or a PD-L1 inhibitor, and a pharmaceutically acceptable carrier and / or excipient.

[0184] In one or more embodiments of the present invention, in the drug combination, the PARP7 inhibitor, the platinum complex and the optional PD-1 inhibitor or PD-L1 inhibitor are present in the same pharmaceutical composition, or the PARP7 inhibitor, the platinum complex and the optional PD-1 inhibitor or PD-L1 inhibitor are present in different pharmaceutical compositions.

[0185] In one or more embodiments of the present invention, the pharmaceutical combination comprises:

[0186] (i) a first pharmaceutical composition comprising a PARP7 inhibitor, a pharmaceutically acceptable carrier and / or excipient;

[0187] (ii) a second pharmaceutical composition comprising a platinum complex, a pharmaceutically acceptable carrier and / or excipient; and

[0188] Optional (iii) a third pharmaceutical composition comprising a PD-1 inhibitor or a PD-L1 inhibitor, a pharmaceutically acceptable carrier and / or excipient.

[0189] Alternatively, the drug combination comprises:

[0190] A single pharmaceutical composition comprising a PARP7 inhibitor, a platinum complex, an optional PD-1 inhibitor or a PD-L1 inhibitor, and a pharmaceutically acceptable carrier and / or excipient.

[0191] One or more embodiments of the present invention provide use of the pharmaceutical combination of the present invention in treating and / or preventing solid tumors and / or hematological tumors.

[0192] One or more embodiments of the present invention provide a method for treating and / or preventing solid tumors and / or hematological tumors, comprising administering to a patient a therapeutically effective dose of the pharmaceutical combination of the present invention.

[0193] In one or more embodiments of the present invention, in the use, the PARP7 inhibitor, the CTLA-4 inhibitor, and the optional PD-1 inhibitor or PD-L1 inhibitor are administered simultaneously or separately.

[0194] In one or more embodiments of the present invention, in the use, the PARP7 inhibitor, the platinum complex, and the optional PD-1 inhibitor or PD-L1 inhibitor are administered simultaneously or separately.

[0195] In one or more embodiments of the present invention, in the use, the PARP7 inhibitor is administered orally, with a dosage frequency of three times a day, twice a day, once a day, once every two days, once every three days, once every four days, once every five days, once every six days, once a week, once every two weeks, once every three weeks, once every four weeks, preferably twice a day or once a day.

[0196] In one or more embodiments of the present invention, in the use, the total daily dose of the PARP7 inhibitor is selected from 50-1500 mg, preferably 100-1000 mg, measured as the free base.

[0197] In one or more embodiments of the present invention, the solid tumor is selected from breast cancer, central nervous system cancer, uterine cancer, cervical cancer, kidney cancer, adrenal cancer, lung cancer, esophageal cancer, ovarian cancer, pancreatic cancer, liver cancer, prostate cancer, testicular cancer, gastric cancer, head and neck cancer, laryngeal cancer, urinary tract cancer, bladder cancer, colon cancer, rectal cancer, thyroid cancer, bone cancer, epithelial cancer, bile duct cancer, gallbladder cancer, skin cancer, mesothelioma, basal cell carcinoma, adenoid cystic carcinoma, leiomyosarcoma, gastrointestinal stromal tumor, Ewing sarcoma, Kaposi sarcoma or PARP7 amplified advanced solid tumor.

[0198] In one or more embodiments of the present invention, the blood tumor is selected from leukemia, myeloma and lymphoma. Exemplary include Hodgkin's lymphoma or non-Hodgkin's lymphoma, multiple myeloma, B-cell lymphoma, small lymphocytic lymphoma, T-cell lymphoma, hairy cell lymphoma, Burkett's lymphoma, acute lymphocytic leukemia, acute myeloid leukemia, chronic lymphocytic leukemia, chronic myeloid leukemia.

[0199] In one or more embodiments of the present invention, the lung cancer is preferably non-small cell lung cancer or neuroendocrine lung cancer.

[0200] In one or more embodiments of the present invention, the non-small cell lung cancer is preferably lung squamous cell carcinoma or lung adenocarcinoma.

[0201] In one or more embodiments of the present invention, the breast cancer is preferably hormone receptor-positive (HR+) breast cancer.

[0202] In one or more embodiments of the present invention, the esophageal cancer is preferably esophageal squamous cell carcinoma or esophageal adenocarcinoma.

[0203] In one or more embodiments of the present invention, the head and neck cancer is preferably head and neck squamous cell carcinoma.

[0204] In one or more embodiments of the present invention, the uterine cancer is preferably endometrial cancer.

[0205] In one or more embodiments of the present invention, the central nervous system cancer is preferably glioma.

[0206] In one or more embodiments of the present invention, the liver cancer is preferably hepatocellular carcinoma.

[0207] In one or more embodiments of the present invention, the B-cell lymphoma is preferably diffuse large B-cell lymphoma.

[0208] Unless stated otherwise, the terms used in the specification and claims have the following meanings.

[0209] "Optional" or "optionally" or "selective" or "selectively" means that the event or situation described subsequently may but need not occur, and the description includes cases where the event or situation occurs as well as cases where it does not occur. For example, "optionally a third active ingredient, a PD-1 inhibitor or a PD-L1 inhibitor" means that the active ingredient, a PD-1 inhibitor or a PD-L1 inhibitor, may but need not be present, and the description includes cases where the PD-1 inhibitor or PD-L1 inhibitor is present as well as cases where the PD-1 inhibitor or PD-L1 inhibitor is not present. BRIEF DESCRIPTION OF THE DRAWINGS

[0210] Figure 1 shows the curve of tumor volume changes in tumor-bearing mice (1).

[0211] Figure 2 shows the body weight change curve of tumor-bearing mice (1).

[0212] Figure 3 shows the curve of tumor volume changes in tumor-bearing mice (2).

[0213] Figure 4 shows the body weight change curve of tumor-bearing mice (2). DETAILED DESCRIPTION

[0214] The following describes in detail the implementation process of the present invention and the beneficial effects produced by it through specific examples, which is intended to help readers better understand the essence and characteristics of the present invention and is not intended to limit the scope of implementation of this case.

[0215] Compound ① in the embodiment is compound 1 of PCT application WO2022242750, and compound ① is prepared according to its preparation method.

[0216] The present invention is described in further detail below with reference to the accompanying drawings:

[0217] Drug efficacy test in CT26 mouse tumor model

[0218] 1. Experimental Procedure

[0219] Cell culture

[0220] Mouse colon cancer cells CT26 were purchased from Beina Biotechnology (Cat. No. BNCC287983) and cultured in DMEM supplemented with 10% fetal bovine serum and 1% penicillin-streptomycin at 37°C in a cell culture incubator containing 5% CO2. When cells reached the exponential growth phase, they were trypsinized, harvested, counted, and plated.

[0221] 1.2. Grouping and Dosing

[0222] After BALB / c mice were adapted to the laboratory environment, CT26 cell suspension was inoculated subcutaneously on the right rib cage of the mice, with 1×10 6 cells / mouse, the inoculation volume is 0.1mL. When the tumor grows to 53mm 3 Around 48 animals were screened and enrolled. They were divided into six groups of eight animals each according to tumor size using a sigmoid grouping method. The day of grouping was designated experimental day 0 (PG-D0), and dosing began on day 1. The grouping and dosing schedule is detailed in Table 1. Anti-mCTLA-4 was purchased from BioXcell, clone number 9D9, catalog number #BP0164.

[0223] Table 1 Dosage regimen Note: ig refers to oral administration; ip refers to intraperitoneal administration; BID refers to twice-daily administration; BIW refers to twice-weekly administration; Q3D refers to once every 3 days.

[0224] 2. Determination method

[0225] Tumor volume

[0226] The tumor diameter was measured with a vernier caliper twice a week, the tumor volume was calculated, and the tumor growth curve was drawn. The calculation formula for tumor volume (V) was:

[0227] V=1 / 2×a×b 2 , where a and b represent the long diameter and short diameter of the tumor, respectively.

[0228] Mouse weight

[0229] During the drug treatment period, the mice were weighed twice a week.

[0230] 3. Experimental results and conclusions

[0231] As shown in Figures 1 and 2 , compound ① combined with an anti-mCTLA-4 antibody exhibited superior in vivo anti-tumor efficacy compared to the anti-mCTLA-4 antibody alone, and exhibited favorable safety and tolerability, demonstrating that the drug combination of the present invention exhibits significant synergistic effects.

[0232] As shown in Figures 3 and 4 , compound ① combined with cisplatin has a better in vivo anti-tumor effect than cisplatin alone, and exhibits good safety and tolerability, indicating that the drug combination of the present invention has a significant synergistic effect.

[0233] The specification of the present invention describes the specific implementation scheme in detail. Those skilled in the art should recognize that the above implementation scheme is exemplary and cannot be understood as limiting the present invention. For those skilled in the art, without departing from the principles of the present invention, by making several improvements and modifications to the present invention, the technical solutions obtained by these improvements and modifications also fall within the scope of protection of the claims of the present invention.

Claims

1. A drug combination, characterized in that The drug combination comprises: a first active ingredient, a PARP7 inhibitor, a second active ingredient, a CTLA-4 inhibitor or a platinum complex, and an optional third active ingredient, a PD-1 inhibitor or a PD-L1 inhibitor.

2. The drug combination according to claim 1, characterized in that The drug combination comprises: (a) a PARP7 inhibitor, (b) a CTLA-4 inhibitor, and optionally (c) a PD-1 inhibitor or a PD-L1 inhibitor.

3. The drug combination according to claim 2, characterized in that The drug combination comprises: (a) a PARP7 inhibitor, and (b) a CTLA-4 inhibitor.

4. The pharmaceutical combination according to claim 1, characterized in that The drug combination comprises: (a) a PARP7 inhibitor, (b) a platinum complex, and optionally (c) a PD-1 inhibitor or a PD-L1 inhibitor.

5. The pharmaceutical combination according to claim 4, characterized in that The drug combination comprises: (a) a PARP7 inhibitor, and (b) a platinum complex.

6. The pharmaceutical combination according to claim 1, wherein The PARP7 inhibitor is selected from RBN-2397, ONO-7119, QLS1103, JAB-26766, NSP-5020, NSP-5033, EB400 or a compound of formula (I) or a pharmaceutically acceptable salt, stereoisomer or deuterated substance thereof: in: X1 is NH, O or a 4- to 6-membered heterocyclic ring containing 1 to 3 heteroatoms selected from N and O; X2 is O or a single bond; X3 and X4 are each independently C or N; R 1a , R 1b Each independently is H, D or C 1-6 Alkyl; or R 1a , R 1b Together with the carbon atom to which it is attached, it forms a 3- to 5-membered cycloalkyl group; R 2a , R 2b Each independently is H, D or C 1-6 Alkyl; or R 2a , R 2b With the carbon atom connected to form 3 to 5 cycloalkyl; R3 is H, D, C 1-6 Alkyl, halogen or cyano, the C 1-6 The alkyl group is optionally substituted with 1 to 3 halogens; R4 and R5 are each independently H, D or C 1-6 Alkyl; or R4, R5 and the connected carbon atom form a 3 to 5-membered cycloalkyl; R6 and R7 are each independently H, D or C 1-6 Alkyl; or R6, R7 and the connected carbon atom form C=O; R8 and R9 are each independently H, D or C 1-6 Alkyl; or R8, R9 and the connected carbon atom form C=O; or R8 and R9 and the connected carbon atom form a 3-5 membered cycloalkyl; R 10 Each independently is C 1-6 Alkyl, C 1-6 Alkoxy, CONR 10a R 10b , halogen, cyano, S(O)2R 10c , SR 10d or a 3- to 5-membered cycloalkyl group, the C 1-6 Alkyl, C 1-6 Alkoxy is optionally substituted with 1 to 3 halogens; R 10a , R 10b , R 10c , R 10d Each independently is H, D or C 1-6 alkyl; A is R a C 1-6 Alkyl, C 3-5 Cycloalkyl, halogen or cyano, the C 1-6 The alkyl group is optionally substituted with 1 to 3 halogens; B is a 5- to 10-membered carbocyclic or heterocyclic ring containing 1 to 3 heteroatoms selected from N, O and S; C is a 5- to 6-membered heterocyclic ring containing 1 to 3 N heteroatoms; m is 1, 2 or 3; n is 0, 1, 2 or 3; p is 0, 1, 2 or 3.

7. The pharmaceutical combination according to claim 6, wherein: X1 is NH, O or a 4- to 6-membered heterocyclic ring containing 1 to 3 heteroatoms selected from N and O; X2 is O or a single bond; X3 and X4 are each independently C or N; R 1a , R 1b Each independently is H, D or C 1-6 alkyl; R 2a , R 2b Each independently is H, D or C 1-6 Alkyl; or R 2a , R 2b Together with the carbon atom to which it is attached, it forms a 3- to 5-membered cycloalkyl group; R3 is H, D, C 1-6 Alkyl, halogen or cyano, the C 1-6 The alkyl group is optionally substituted with 1 to 3 halogens; R4 and R5 are each independently H, D or C 1-6 Alkyl; or R4, R5 and the connected carbon atom form a 3 to 5-membered cycloalkyl; R6 and R7 are each independently H, D or C 1-6 alkyl; R8 and R9 are each independently H, D or C 1-6 Alkyl; or R8, R9 and the connected carbon atom form C=O; R 10 Each independently is C 1-6 Alkyl, C 1-6 Alkoxy, CONR 10a R 10b , halogen, cyano, S(O)2R 10c , SR 10d or a 3- to 5-membered cycloalkyl group, the C 1-6 Alkyl, C 1-6 The alkoxy group is optionally substituted with 1 to 3 halogens; R 10a , R 10b , R 10c , R 10d Each independently is H, D or C 1-6 alkyl; A is R a C 1-6 Alkyl, C 3-5 Cycloalkyl, halogen or cyano, the C 1-6 The alkyl group is optionally substituted with 1 to 3 halogens; B is a 5- to 6-membered carbocyclic or heterocyclic ring containing 1 to 3 heteroatoms selected from N, O and S; C is a 5- to 6-membered heterocyclic ring containing 1 to 3 N heteroatoms; m is 1, 2 or 3; n is 0, 1, 2 or 3; p is 0, 1, 2 or 3.

8. The pharmaceutical combination according to claim 6, wherein the PARP7 inhibitor is selected from RBN-2397, ONO-7119, QLS1103, JAB-26766, NSP-5020, NSP-5033, EB400 or a compound represented by formula (I-1) or a pharmaceutically acceptable salt, stereoisomer or deuterated substance thereof, in: X1 is NH or a 4- to 6-membered heterocyclic ring containing 1 to 3 heteroatoms selected from N and O; X2 is 0; X3 and X4 are each independently C or N; R 1a , R 1b Each independently is H, D or C 1-6 alkyl; R 2a , R 2b Each independently is H, D or C 1-6 alkyl; R3 is H, D, C 1-6 Alkyl or halogen, the C 1-6 The alkyl group is optionally substituted with 1 to 3 halogens; R4 and R5 are each independently H, D or C 1-6 alkyl; R6 and R7 are each independently H, D or C 1-6 alkyl; R8 and R9 are each independently H, D or C 1-6 Alkyl; or R8 and R9 form C=O with the carbon atom to which they are connected; R 10 C 1-6 Alkyl, C 1-6 Alkoxy, cyano or SR 10d , the C 1-6 Alkyl, C 1-6 Alkoxy is optionally substituted with 1 to 3 halogens; R 10d H, D or C 1-6 alkyl; A is B is a 5- to 6-membered carbocyclic or heterocyclic ring containing 1 to 3 heteroatoms selected from N, O and S; C is a 5- to 6-membered heterocyclic ring containing 1 to 3 N heteroatoms; m is 1, 2 or 3; n is 0, 1, 2 or 3.

9. The pharmaceutical combination according to claim 6, wherein the PARP7 inhibitor is selected from RBN-2397, ONO-7119, QLS1103, JAB-26766, NSP-5020, NSP-5033, EB400 or a compound represented by formula (I-2) or a pharmaceutically acceptable salt, stereoisomer or deuterated substance thereof, in: X1 is NH; X2 is 0; R 1a , R 1b Each independently is H, D or C 1-6 alkyl; R 2a , R 2b Each independently is H, D or C 1-6 alkyl; R3 is H, D, C 1-6 Alkyl or halogen, the C 1-6 The alkyl group is optionally substituted with 1 to 3 halogens; R4 and R5 are each independently H, D or C 1-6 alkyl; R6 and R7 are each independently H, D or C 1-6 alkyl; R8 and R9 are each independently H, D or C 1-6 Alkyl; or R8 and R9 and the carbon atom to which they are attached form C=O; R 10 C 1-6 Alkyl, C 1-6 Alkoxy, cyano or SR 10d , the C 1-6 Alkyl, C 1-6 Alkoxy is optionally substituted with 1 to 3 halogens; R 10d H, D or C 1-6 alkyl; A is B is a 5- to 6-membered carbocyclic or heterocyclic ring containing 1 to 3 heteroatoms selected from N, O and S; m is 1, 2 or 3; n is 0, 1, 2 or 3.

10. The pharmaceutical combination according to claim 9, wherein: X1 is NH; X2 is 0; R 1a , R 1b Each independently is H, D or C 1-6 alkyl; R 2a , R 2b Each independently is H, D or C 1-6 alkyl; R3 is H, D, C 1-6 Alkyl or halogen, the C 1-6 The alkyl group is optionally substituted with 1 to 3 halogens; R4 and R5 are each independently H, D or C 1-6 alkyl; R6 and R7 are each independently H, D or C 1-6 alkyl; R8 and R9 are each independently H, D or C 1-6 Alkyl, or R8 and R9 form C=O with the carbon atom to which they are attached; R 10 C 1-6 Alkyl, cyano, or SR 10d , the C 1-6 The alkyl group is optionally substituted with 1 to 3 halogens; R 10d H, D or C 1-6 alkyl; A is B is a 5- to 6-membered carbocyclic or heterocyclic ring containing 1 to 3 heteroatoms selected from N, O and S; m is 1, 2 or 3; n is 0, 1, 2 or 3.

11. The pharmaceutical combination according to claim 10, wherein: X1 is selected from NH; X2 is selected from O; R 1a , R 1b Each independently selected from H, D or C 1-6 alkyl; R 2a , R 2b Each independently selected from H, D or C 1-6 alkyl; R3 is H, D, C 1-6 Alkyl or halogen, the C 1-6 The alkyl group is optionally substituted with 1 to 3 halogens; R4 and R5 are each independently H or D; R6 and R7 are each independently H or D; R8 and R9 are each independently H or D; R 10 CF3 or SR 10d ; R 10d H, D or C 1-6 alkyl; A is B is m is 1, 2 or 3; n is 0, 1, 2 or 3.

12. The pharmaceutical combination according to claim 11, wherein: X1 is selected from NH; X2 is selected from O; R 1a , R 1b Each independently selected from H, D or C 1-3 alkyl; R 2a , R 2b Each independently selected from H, D or C 1-3 alkyl; R3 is selected from H, D or CF3; R4 and R5 are each independently selected from H or D; R6 and R7 are each independently selected from H or D; R8 and R9 are each independently selected from H or D; R 10 is CF3; A is B is m is 1, 2 or 3; n is 0, 1 or 2.

13. The pharmaceutical combination according to claim 6, wherein the PARP7 inhibitor is selected from RBN-2397, ONO-7119, QLS1103, JAB-26766, NSP-5020, NSP-5033, EB400 or a compound represented by formula (I-3) or a pharmaceutically acceptable salt, stereoisomer or deuterated substance thereof, in: X1 is NH or a 4- to 6-membered heterocyclic ring containing 1 to 3 heteroatoms selected from N and O; X2 is 0; R 1a , R 1b Each independently is H, D or C 1-6 alkyl; R 2a , R 2b Each independently is H, D or C 1-6 alkyl; R4 and R5 are each independently H, D or C 1-6 alkyl; R6 and R7 are each independently H, D or C 1-6 alkyl; R8 and R9 are each independently H, D or C 1-6 Alkyl; or R8, R9 and the connected carbon atom form C=O; R 10 C 1-6 Alkyl, C 1-6 Alkoxy, cyano or SR 10d , the C 1-6 Alkyl, C 1-6 Alkoxy is optionally substituted with 1 to 3 halogens; R 10d H, D or C 1-6 alkyl; A is B is a 5- to 6-membered carbocyclic or heterocyclic ring containing 1 to 3 heteroatoms selected from N, O and S; m is 1, 2 or 3; n is 0, 1, 2 or 3.

14. The pharmaceutical combination according to claim 13, wherein: X1 is NH or a 4- to 6-membered heterocyclic ring containing 1 to 3 heteroatoms selected from N and O; X2 is 0; R 1a , R 1b Each independently is H, D or C 1-3 alkyl; R 2a , R 2b Each independently is H, D or C 1-3 alkyl; R4 and R5 are each independently H, D or C 1-3 alkyl; R6 and R7 are each independently H, D or C 1-3 alkyl; R8 and R9 are each independently H, D or C 1-3 Alkyl; or R8 and R9 form C=O with the carbon atom to which they are connected; R 10 C 1-6 Alkyl, cyano or SR 10d , the C 1-6 The alkyl group is optionally substituted with 1 to 3 halogens; R 10d H, D or C 1-6 alkyl; A is B is m is 1, 2 or 3; n is 0, 1 or 2.

15. The pharmaceutical combination according to claim 14, wherein: X1 is NH; X2 is 0; R 1a , R 1b Each independently is H, D or C 1-3 alkyl; R 2a , R 2b Each independently is H or D; R4 and R5 are each independently H or D; R6 and R7 are each independently H or D; R8 and R9 are each independently H or D; R 10 is CF3; A is B is m is 1, 2 or 3; n is 0, 1 or 2.

16. The pharmaceutical combination according to any one of claims 1 to 15, wherein the PARP7 inhibitor is selected from RBN-2397, ONO-7119, QLS1103, JAB-26766, NSP-5020, NSP-5033, EB400 or the following compounds or pharmaceutically acceptable salts, stereoisomers or deuterated derivatives thereof:

17. The pharmaceutical combination according to claim 1, wherein The CTLA-4 inhibitor is selected from one or a combination of antibodies, small molecule compounds, microRNA, siRNA, and shRNA.

18. The pharmaceutical combination according to claim 17, wherein The CTLA-4 inhibitor antibody is selected from one or a combination of ipilimumab, tremelimumab, gotistobart, SHR-8068, ADG-126, ADG-116, YH-001, XTX-101, BMS-986218, porustobart, botensilimab, BA-3071, KD-6001, Zaliferelimab, Quavonlimab, REGN-4659, IMM-27M, MT-8421, BCD-145, and KN-044.

19. The pharmaceutical combination according to claim 1, wherein The platinum complex is selected from one or a combination of cisplatin, carboplatin, cyclothioplatin, nedaplatin, oxaliplatin and lobaplatin.

20. The pharmaceutical combination according to claim 1, wherein the PD-1 inhibitor or PD-L1 inhibitor is selected from Pembrolizumab, Nivolumab, Serplulimab, Pidilizumab, Lambrolizumab, Atezolizumab, Toripalimab, Sintilimab, Tislelizumab, Camrelizumab, Penpulimab, Sepalimab, Zimberelimab, Envafolimab, Sugemalimab, Dostarlimab, Cadonilimab, Cemiplimab, Retifanlimab, BMS-986213, HX-008, Geptanolimab, Prolgolimab, Socazolimab, Avelumab, Adebrelimab, or Durvalumab.

21. The pharmaceutical combination according to claim 1, characterized in that The PARP7 inhibitor, the CTLA-4 inhibitor and the optional PD-1 inhibitor or PD-L1 inhibitor are present in the same pharmaceutical composition, or the PARP7 inhibitor, the CTLA-4 inhibitor and the optional PD-1 inhibitor or PD-L1 inhibitor are present in different pharmaceutical compositions, respectively.

22. The pharmaceutical combination according to claim 1, characterized in that The PARP7 inhibitor, the platinum complex and the optional PD-1 inhibitor or PD-L1 inhibitor are present in the same pharmaceutical composition, or the PARP7 inhibitor, the platinum complex and the optional PD-1 inhibitor or PD-L1 inhibitor are present in different pharmaceutical compositions, respectively.

23. Use of the pharmaceutical combination according to any one of claims 1 to 22 in the treatment and / or prevention of solid tumors and / or hematological tumors.

24. The use according to claim 23, characterized in that The PARP7 inhibitor, the CTLA-4 inhibitor and the optional PD-1 inhibitor or PD-L1 inhibitor are administered simultaneously or separately.

25. The use according to claim 23, characterized in that The PARP7 inhibitor, the platinum complex and the optional PD-1 inhibitor or PD-L1 inhibitor are administered simultaneously or separately.

26. The use according to claim 23, characterized in that The solid tumor is selected from breast cancer, central nervous system cancer, uterine cancer, cervical cancer, kidney cancer, adrenal cancer, lung cancer, esophageal cancer, ovarian cancer, pancreatic cancer, liver cancer, prostate cancer, testicular cancer, gastric cancer, head and neck cancer, laryngeal cancer, urinary tract cancer, bladder cancer, colon cancer, rectal cancer, thyroid cancer, bone cancer, epithelial cancer, bile duct cancer, gallbladder cancer, skin cancer, mesothelioma, basal cell carcinoma, adenoid cystic carcinoma, leiomyosarcoma, gastrointestinal stromal tumor, Ewing sarcoma, Kaposi sarcoma or PARP7 amplified advanced solid tumor.

27. The use according to claim 23, characterized in that The blood tumor is selected from leukemia, myeloma or lymphoma, preferably selected from Hodgkin's lymphoma, non-Hodgkin's lymphoma, multiple myeloma, B-cell lymphoma, small lymphocytic lymphoma, T-cell lymphoma, hairy cell lymphoma, Burkett's lymphoma, acute lymphocytic leukemia, acute myeloid leukemia, chronic lymphocytic leukemia or chronic myeloid leukemia.

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