Use of antibody-drug conjugate in preparation of drug for treating lung cancer

Abstract

Use of an antibody-drug conjugate in the preparation of a drug for treating lung cancer.

Description

Use of an antibody drug conjugate in the preparation of a medicament for treating lung cancer TECHNICAL FIELD

[0001] The present application belongs to the field of medicine, and relates to a method for treating cancer using an antibody drug conjugate. Specifically, the present application provides a method for treating cancer using an antibody drug conjugate, and use of the antibody drug conjugate in the preparation of a medicament for treating cancer. BACKGROUND

[0002] According to global cancer data in 2020, there were 19.29 million new cancer cases worldwide in 2020, and 9.96 million deaths, which seriously threatened the health of people worldwide.

[0003] Lung cancer is the second most common malignant tumor in the world in terms of incidence, and ranks first in terms of mortality. Lung cancer is the second most common malignant tumor in the world in terms of incidence, and ranks first in terms of mortality. In 2020, there were about 2.207 million new cases of lung cancer worldwide, and about 1.796 million deaths. In 2020, there were about 816,000 new cases of lung cancer in China, and about 715,000 deaths, with the incidence and mortality rates both ranking first among domestic malignant tumors. Non-small cell lung cancer (NSCLC) accounts for about 80-85% of all lung cancers, and small cell lung cancer (SCLC) accounts for about 15% of all lung cancer cases.

[0004] About 70% of NSCLC patients are in the locally advanced or distant metastatic stage at the time of diagnosis, and cannot undergo surgical resection. Even patients who have undergone surgical resection in the early stage, most have distant metastasis at the time of recurrence. The 5-year survival rate of metastatic NSCLC patients is less than 5%. The median survival of patients with advanced NSCLC who cannot undergo surgical resection is about 15 months. The treatment of targeted drugs for driver gene-positive greatly improves the tumor remission time and overall survival time of NSCLC. With the emergence of drug resistance genes, the treatment of patients in the later line is still mainly chemotherapy, and most of them have poor efficacy, with a median survival of 8.3-18.2 months. For NSCLC patients without driver genes (including squamous cell carcinoma and non-squamous cell carcinoma), the first-line treatment is chemotherapy ± immune checkpoint inhibitors. There is no standard treatment for second-line treatment, and the choice is poor in efficacy.

[0005] Small cell lung cancer (SCLC), accounting for about 15% of lung cancer, has a five-year survival rate of less than 7%. When the tumor lesion is limited to the ipsilateral chest cavity, combined with ipsilateral pleural effusion and lymph node metastasis, it is called limited stage small cell lung cancer (LS-SCLC). When the cancer cells have spread to the bilateral lung, the chest cavity or the advanced stage of distant organs (such as liver, brain, bone), it is called extensive stage small cell lung cancer (ES-SCLC). Although new treatment measures such as molecular targeted drugs and immune checkpoint inhibitors are constantly developing, the treatment strategy for small cell lung cancer patients has not had a significant breakthrough in the past few decades. Traditional radiotherapy is still the first-line treatment for small cell lung cancer patients. The standard first-line concurrent chemoradiotherapy can achieve about 10-15 months of progression-free survival in patients with limited stage small cell lung cancer. The vast majority of limited stage small cell lung cancer will eventually progress, and the overall survival is less than 3 years. At present, according to the guidelines recommended, patients only need to receive observation and follow-up after completing concurrent chemoradiotherapy, and there is no good consolidation treatment option, so it is necessary to develop effective consolidation treatment options to improve the prognosis of patients with limited stage small cell lung cancer, and new antitumor drugs are urgently needed.

[0006] Antibody drug conjugate (ADC) is a kind of drug that couples monoclonal antibody and small molecule cytotoxin through chemical linker. It combines with the antigen on the surface of target cells through the guidance of monoclonal antibody, and delivers small molecule cytotoxin to target cells, so as to kill target cells. ADC combines the high targeting of antibody and the strong killing of cytotoxic drugs, and becomes the research and development hotspot of tumor targeted therapy. The mechanism of action of ADC includes: 1) toxin effect: this is the main mechanism of action of ADC against tumors. Through the specific binding of the antibody part of ADC to the antigen on the surface of target cells, the ADC-antigen complex enters the target cells through endocytosis, and the small molecule cytotoxic drug is released in the lysosome. Finally, the cytotoxic drug induces apoptosis by damaging DNA or acting on tubulin protein; 2) bystander effect: after killing target cells, small molecule cytotoxic drugs penetrate into the extracellular space and kill surrounding cells; 3) antibody-dependent cell-mediated cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC): the ADCC and CDC of the antibody itself in ADC are also one of the killing effects of ADC.

[0007] B7-H3 (B7 homolog 3 protein), also known as CD276, is an important immune checkpoint molecule of the B7-CD28 family, which plays an important role in tumor growth and immune regulation. Studies have reported that B7-H3 may play a dual role in the immune system. B7-H3 mRNA is widely expressed in almost all human immune and non-immune tissue organs, but its protein expression in normal tissues is very limited, with certain low-level expression in breast, prostate, testis, liver, lung, placenta and some lymphoid organs. The difference between the wide expression of B7-H3 mRNA and the limited distribution of protein indicates a complex post-transcriptional regulation mechanism. At present, more and more studies have reported that B7-H3 protein can be abnormally highly expressed in various tumor cells / tissues and tumor vasculature. The characteristics that B7-H3 protein is not expressed or lowly expressed in normal tissues, but abnormally highly expressed in many tumor cells / tissues and tumor vasculature, make it an ideal target for tumor immunotherapy / targeted therapy. At present, there are many therapeutic drugs targeting B7-H3 in the clinical research stage, among which the ADC drug shows excellent prospects. SUMMARY

[0008] The use of the antibody drug conjugate of the present disclosure in the preparation of a medicament for treating lung cancer, the structure of the antibody drug conjugate is shown as formula (I):

[0009] In formula (I), n is a non-zero integer or a small number between 1 and 10, preferably a small number or an integer between 1 and 8, preferably a small number or an integer between 2 and 8, more preferably an integer or a small number between 3 and 8.

[0010] Pc is an anti-B7H3 antibody or an antigen binding fragment thereof.

[0011] In some embodiments, the anti-B7H3 antibody or antigen binding fragment thereof comprises heavy chain HCDR1, HCDR2, HCDR3 as shown in the amino acid sequences of SEQ ID NO: 01, 02 and 03, respectively, and light chain LCDR1, LCDR2 and LCDR3 as shown in the amino acid sequences of SEQ ID NO: 04, 05 and 06, respectively.

[0012] In the present application, the amino acid sequences of the CDRs listed above are shown according to the Kabat definition rule. However, it is well known to those skilled in the art that the CDRs of an antibody can be defined by various methods in the art. Although the scope of protection of the present application is based on the sequences shown according to the Kabat definition rule, the amino acid sequences corresponding to the CDRs according to other definition rules should also fall within the scope of protection of the present application.

[0013] Wherein, the aforementioned CDR sequences are shown in the following table:

[0014] Table 1 CDR sequences of each heavy chain and light chain

[0015] Note: The CDR sequences are derived from the rules shown in Kabat definition.

[0016] Preferably, the anti-B7H3 antibody or antigen-binding fragment thereof is selected from a humanized antibody or fragment thereof.

[0017] In some alternative embodiments, the anti-B7H3 antibody or antigen-binding fragment thereof described in the present application is an antibody fragment selected from the group consisting of Fab, Fab'-SH, Fv, scFv, and (Fab')2 fragments.

[0018] In some alternative embodiments, the anti-B7H3 antibody or antigen-binding fragment thereof described in the present application comprises a heavy chain constant region of human IgG1, IgG2, IgG3 or IgG4 isotype, preferably a heavy chain constant region of IgG1 or IgG4 isotype.

[0019] In other alternative embodiments, the anti-B7H3 antibody or antigen-binding fragment thereof comprises a light chain constant region of kappa or lambda.

[0020] Further, the heavy chain variable region sequence of the anti-B7H3 antibody or antigen-binding fragment thereof is preferably the sequence shown in SEQ ID NO: 07 or a variant thereof, and the light chain variable region sequence is preferably the sequence shown in SEQ ID NO: 08 or a variant thereof.

[0021] The sequences of the heavy and light chain variable regions of the aforementioned anti-B7H3 antibody or antigen-binding fragment thereof are as follows:

[0022] Light chain variable region sequence

[0023] Note: The order is FR1-CDR1-FR2-CDR2-FR3-CDR3-FR4, the italicized sequences in the sequence are FR sequences, and the underlined sequences are CDR sequences, wherein the CDR sequences are derived from the rules shown in Kabat definition.

[0024] Further, the heavy chain sequence of the anti-B7H3 antibody or antigen-binding fragment thereof is preferably the sequence shown in SEQ ID NO: 09 or a variant thereof, and the light chain sequence is preferably the sequence shown in SEQ ID NO: 10 or a variant thereof.

[0025] The sequences of the heavy and light chains of the aforementioned anti-B7H3 antibody or antigen-binding fragment thereof are as follows:

[0026] Heavy chain (IgGl) amino acid sequence: (SEQ ID NO: 09)

[0027] Light chain (lambda) amino acid sequence: (SEQ ID NO: 10)

[0028] In some embodiments, the antibody drug conjugate is administered once every week, once every two weeks, once every three weeks, once every four weeks, once a month, or once every three to six months.

[0029] Preferably, the antibody drug conjugate is administered once every two weeks, once every three weeks, or once every four weeks; more preferably, once every three weeks.

[0030] In some embodiments, the antibody drug conjugate is administered at a dose of 0.1 mg / kg to 20 mg / kg, preferably 0.5 mg / kg to 18 mg / kg, more preferably 1 mg / kg to 16 mg / kg, further preferably 4 mg / kg to 12 mg / kg.

[0031] In some embodiments, the dose of the antibody drug conjugate is selected from the group consisting of 4.0 mg / kg, 4.1 mg / kg, 4.2 mg / kg, 4.3 mg / kg, 4.4 mg / kg, 4.5 mg / kg, 4.6 mg / kg, 4.7 mg / kg, 4.8 mg / kg, 4.9 mg / kg, 5 mg / kg, 5.1 mg / kg, 5.2 mg / kg, 5.3 mg / kg, 5.4 mg / kg, 5.5 mg / kg, 5.6 mg / kg, 5.7 mg / kg, 5.8 mg / kg, 5.9 mg / kg, 6.0 mg / kg, 6.1 mg / kg, 6.2 mg / kg, 6.3 mg / kg, 6.4 mg / kg, 6.5 mg / kg, 6.6 mg / kg, 6.7 mg / kg, 6.8 mg / kg, 6.9 mg / kg, 7 mg / kg, 7.1 mg / kg, 7.2 mg / kg, 7.3 mg / kg, 7.4 mg / kg, 7.5 mg / kg, 7.6 mg / kg, 7.7 mg / kg, 7.8 mg / kg, 7.9 mg / kg, 8 mg / kg, 8.1 mg / kg, 8.2 mg / kg, 8.3 mg / kg, 8.4 mg / kg, 8.5 mg / kg, 8.6 mg / kg, 8.7 mg / kg, 8.8 mg / kg, 8.9 mg / kg, 9 mg / kg, 9.1 mg / kg, 9.2 mg / kg, 9.3 mg / kg, 9.4 mg / kg, 9.5 mg / kg, 9.6 mg / kg, 9.7 mg / kg, 9.8 mg / kg, 9.9 mg / kg, 10 mg / kg, 10.1 mg / kg, 10.2 mg / kg, 10.3 mg / kg, 10.4 mg / kg, 10.5 mg / kg, 10.6 mg / kg, 10.7 mg / kg, 10.8 mg / kg, 10.9 mg / kg, 11 mg / kg, 11.1 mg / kg, 11.2 mg / kg, 11.3 mg / kg, 11.4 mg / kg, 11.5 mg / kg, 11.6 mg / kg, 11.7 mg / kg, 11.8 mg / kg, 11.9 mg / kg, or 12 mg / kg.

[0032] In some embodiments, the dose of the antibody drug conjugate is selected from the group consisting of 4.0 mg / kg, 6.0 mg / kg, 8.0 mg / kg, 10.0 mg / kg, 12.0 mg / kg.

[0033] In some embodiments, the antibody drug conjugate is administered intravenously at a dose of 4 mg / kg to 12 mg / kg, with a frequency of once every two weeks, once every three weeks, or once every four weeks.

[0034] In some embodiments, the antibody drug conjugate is administered intravenously at a dosage of 4.0 mg / kg, 6.0 mg / kg, 8.0 mg / kg, 10.0 mg / kg, 12.0 mg / kg, once every two weeks, once every three weeks, or once every four weeks.

[0035] In some embodiments, the antibody drug conjugate is administered intravenously at a dosage of 4.0 mg / kg, 6.0 mg / kg, 8.0 mg / kg, 10.0 mg / kg, 12.0 mg / kg, once every three weeks.

[0036] In some embodiments, the antibody drug conjugate is administered intravenously at a dosage of 8.0 mg / kg, once every three weeks.

[0037] In some embodiments, the antibody drug conjugate is administered intravenously at a dosage of 10.0 mg / kg, once every three weeks.

[0038] In some embodiments, the lung cancer is selected from the group consisting of small cell lung cancer, non-small cell lung cancer, lung squamous cell carcinoma, lung adenocarcinoma, large cell lung cancer; preferably the lung cancer is selected from the group consisting of limited stage small cell lung cancer, extensive stage small cell lung cancer, non-small cell lung squamous carcinoma, non-small cell lung adenocarcinoma, non-squamous non-small cell lung cancer.

[0039] In some embodiments, the lung cancer is selected from the group consisting of small cell lung cancer. In some embodiments, the lung cancer is selected from the group consisting of non-small cell lung cancer. In some embodiments, the lung cancer is selected from the group consisting of lung squamous cell carcinoma. In some embodiments, the lung cancer is selected from the group consisting of lung adenocarcinoma. In some embodiments, the lung cancer is selected from the group consisting of large cell lung cancer.

[0040] In some embodiments, the lung cancer is selected from the group consisting of limited stage small cell lung cancer. In some embodiments, the lung cancer is selected from the group consisting of extensive stage small cell lung cancer. In some embodiments, the lung cancer is selected from the group consisting of non-small cell lung squamous carcinoma. In some embodiments, the lung cancer is selected from the group consisting of non-small cell lung adenocarcinoma. In some embodiments, the lung cancer is selected from the group consisting of non-squamous non-small cell lung cancer.

[0041] In some embodiments, the lung cancer is selected from the group consisting of limited stage small cell lung cancer, the antibody drug conjugate is administered intravenously at a dosage of 8.0 mg / kg, once every three weeks.

[0042] In some embodiments, the lung cancer is selected from the group consisting of extensive stage small cell lung cancer, the antibody drug conjugate is administered intravenously at a dosage of 8.0 mg / kg, once every three weeks.

[0043] In some embodiments, the lung cancer is selected from non-small cell lung squamous carcinoma, the antibody drug conjugate is administered via intravenous administration, the administration frequency is once every three weeks, and the administration dosage is 8.0 mg / kg.

[0044] In some embodiments, the lung cancer is selected from non-small cell lung adenocarcinoma, the antibody drug conjugate is administered via intravenous administration, the administration frequency is once every three weeks, and the administration dosage is 8.0 mg / kg.

[0045] In some embodiments, the lung cancer is selected from non-squamous non-small cell lung cancer, the antibody drug conjugate is administered via intravenous administration, the administration frequency is once every three weeks, and the administration dosage is 8.0 mg / kg.

[0046] In some embodiments, the lung cancer is selected from limited-stage small cell lung cancer, the antibody drug conjugate is administered via intravenous administration, the administration frequency is once every three weeks, and the administration dosage is 10.0 mg / kg.

[0047] In some embodiments, the lung cancer is selected from extensive-stage small cell lung cancer, the antibody drug conjugate is administered via intravenous administration, the administration frequency is once every three weeks, and the administration dosage is 10.0 mg / kg.

[0048] In some embodiments, the lung cancer is selected from non-small cell lung squamous carcinoma, the antibody drug conjugate is administered via intravenous administration, the administration frequency is once every three weeks, and the administration dosage is 10.0 mg / kg.

[0049] In some embodiments, the lung cancer is selected from non-small cell lung adenocarcinoma, the antibody drug conjugate is administered via intravenous administration, the administration frequency is once every three weeks, and the administration dosage is 10.0 mg / kg.

[0050] In some embodiments, the lung cancer is selected from non-squamous non-small cell lung cancer, the antibody drug conjugate is administered via intravenous administration, the administration frequency is once every three weeks, and the administration dosage is 10.0 mg / kg.

[0051] In some embodiments, the lung cancer is selected from locally advanced or metastatic non-small cell lung cancer. In some embodiments, the lung cancer is selected from locally advanced or metastatic non-small cell lung cancer that has progressed or is intolerant to standard treatment. In some embodiments, the lung cancer is selected from locally advanced or metastatic non-small cell lung cancer that has progressed or is intolerant to at least one line of treatment.

[0052] In some embodiments, the lung cancer is locally advanced or metastatic non-small cell lung cancer that has progressed or is intolerant to at least one line of treatment without an identified driver mutation. In some embodiments, the lung cancer is locally advanced or metastatic non-small cell lung cancer that has progressed or is intolerant to standard treatment with known presence of EGFR mutation or other driver gene positive.

[0053] In some embodiments, the driver gene comprises: EGFR mutation, ALK, KRAS, ROS1, BRAF, NTRK1 / 2 / 3, HER-2 mutation, MET exon 14 skipping and amplification, RET fusion / mutation.

[0054] In some embodiments, the lung cancer is locally advanced or metastatic non-small cell lung cancer without an identified driver gene that has progressed or is intolerant after at least one line of therapy, the antibody drug conjugate is administered via intravenous administration, the administration frequency is once every three weeks, and the administration dosage is 8.0 mg / kg.

[0055] In some embodiments, the lung cancer is locally advanced or metastatic non-small cell lung cancer without an identified driver gene that has progressed or is intolerant after at least one line of therapy, the antibody drug conjugate is administered via intravenous administration, the administration frequency is once every three weeks, and the administration dosage is 10.0 mg / kg.

[0056] In some embodiments, the lung cancer is extensive stage small cell lung cancer that has progressed or is intolerant after at least one line of therapy.

[0057] In some embodiments, the lung cancer is platinum sensitive recurrent extensive stage small cell lung cancer.

[0058] In some embodiments, the lung cancer is platinum resistant recurrent extensive stage small cell lung cancer.

[0059] In some embodiments, the lung cancer is extensive stage small cell lung cancer that has progressed or is intolerant after at least one line of therapy, the antibody drug conjugate is administered via intravenous administration, the administration frequency is once every three weeks, and the administration dosage is 8.0 mg / kg.

[0060] In some embodiments, the lung cancer is extensive stage small cell lung cancer that has progressed or is intolerant after at least one line of therapy, the antibody drug conjugate is administered via intravenous administration, the administration frequency is once every three weeks, and the administration dosage is 10.0 mg / kg.

[0061] In some embodiments, the lung cancer is platinum sensitive recurrent extensive stage small cell lung cancer, the antibody drug conjugate is administered via intravenous administration, the administration frequency is once every three weeks, and the administration dosage is 8.0 mg / kg.

[0062] In some embodiments, the lung cancer is platinum sensitive recurrent extensive stage small cell lung cancer, the antibody drug conjugate is administered via intravenous administration, the administration frequency is once every three weeks, and the administration dosage is 10.0 mg / kg.

[0063] In some embodiments, the lung cancer is platinum-resistant recurrent extensive-stage small cell lung cancer, the antibody drug conjugate is administered via intravenous administration, the administration frequency is once every three weeks, and the administration dosage is 8.0 mg / kg.

[0064] In some embodiments, the lung cancer is platinum-resistant recurrent extensive-stage small cell lung cancer, the antibody drug conjugate is administered via intravenous administration, the administration frequency is once every three weeks, and the administration dosage is 10.0 mg / kg.

[0065] In some embodiments, the small cell lung cancer is a limited-stage small cell lung cancer; preferably, the small cell lung cancer is a limited-stage small cell lung cancer that has not progressed after receiving chemoradiation (CRT).

[0066] In some embodiments, the lung cancer is selected from a limited-stage small cell lung cancer that has not progressed after receiving chemoradiation (CRT), the antibody drug conjugate is administered via intravenous administration, the administration frequency is once every three weeks, and the administration dosage is 8.0 mg / kg.

[0067] In some embodiments, the lung cancer is selected from a limited-stage small cell lung cancer that has not progressed after receiving chemoradiation (CRT), the antibody drug conjugate is administered via intravenous administration, the administration frequency is once every three weeks, and the administration dosage is 10.0 mg / kg.

[0068] In some embodiments, the type of chemoradiation comprises concurrent chemoradiation (cCRT) and sequential chemoradiation (sCRT).

[0069] In some embodiments, the chemotherapeutic drug of the chemoradiation is selected from cisplatin / carboplatin in combination with etoposide.

[0070] In some embodiments, the radiation frequency of the radiation of the chemoradiation is once daily or twice daily, and the total dose of the radiation is 66 Gy (±10%) or 45 Gy (±10%).

[0071] In some embodiments, the radiation frequency of the radiation of the chemoradiation is once daily, and the total dose of the radiation is 66 Gy (±10%); the radiation frequency of the radiation of the chemoradiation is twice daily, and the total dose of the radiation is 45 Gy (±10%).

[0072] Further, the use comprises selecting the patient based on elevated levels of a cancer-related biomarker.

[0073] In some embodiments, the evaluation of the therapeutic effect comprises detecting the concentration of a biomarker in a patient sample, preferably, the biomarker is selected from soluble B7-H3.

[0074] Further, the relationship between the biomarker and the effectiveness of the antibody drug conjugate is evaluated by detecting the soluble B7-H3 concentration in the blood sample collected from the patient during the screening period, during the treatment period, and at the termination of treatment visit.

[0075] The antibody drug conjugate provided by the present application has improved safety, reduced drug toxicity, can effectively bring potential benefits to patients with limited small cell lung cancer who have not progressed after radiotherapy and chemotherapy, have the opportunity to obtain better prognosis, and can meet the medical needs.

[0076] The term

[0077] In order to facilitate the understanding of the present disclosure, certain technical and scientific terms are defined below. Unless otherwise specifically defined herein, all other technical and scientific terms used herein have the meanings commonly understood by one of ordinary skill in the art to which the present disclosure belongs.

[0078] The present disclosure incorporates the entire content of application WO2020063673 into the present application.

[0079] The term "antibody drug conjugate" refers to the connection of an antibody to a biologically active drug through a stable linking unit. In the present disclosure, "antibody drug conjugate" refers to the connection of a monoclonal antibody or antibody fragment to a biologically active toxic drug through a stable linking unit.

[0080] The term "antibody" refers to an immunoglobulin, which is a four polypeptide chain structure connected by interchain disulfide bonds, consisting of two identical heavy chains and two identical light chains. The amino acid composition and arrangement of the constant region of the heavy chain of immunoglobulin are different, so the antigenicity is also different. Accordingly, immunoglobulin can be divided into five types, or called isotypes of immunoglobulin, namely IgM, IgD, IgG, IgA and IgE, and the corresponding heavy chains are μ chain, δ chain, γ chain, α chain and ε chain. The same type of Ig can be divided into different subtypes according to the difference in amino acid composition of the hinge region and the number and position of heavy chain disulfide bonds, such as IgG, which can be divided into IgG1, IgG2, IgG3 and IgG4. The light chain is divided into κ chain or λ chain by the constant region. Each of the five types of Ig can have κ chain or λ chain.

[0081] The sequences of the heavy and light chains of an antibody near the N-terminus are highly variable and form the variable region (Fv region); the remaining amino acid sequences near the C-terminus are relatively stable and form the constant region. The variable region includes three hypervariable regions (HVR) and four relatively conserved framework regions (FR). The three hypervariable regions determine the specificity of the antibody, also known as the complementarity-determining region (CDR). Each light chain variable region (LCVR) and heavy chain variable region (HCVR) is composed of three CDR regions and four FR regions, arranged in the order of FR1, CDR1, FR2, CDR2, FR3, CDR3, FR4 from the amino terminus to the carboxyl terminus. The three CDR regions of the light chain are referred to as LCDR1, LCDR2, and LCDR3; the three CDR regions of the heavy chain are referred to as HCDR1, HCDR2, and HCDR3.

[0082] In the present disclosure, the amino acid sequences of the CDRs described above are shown according to the Kabat definition. However, it is well known in the art that CDRs of antibodies can be defined in various ways in the art, such as Chothia based on the three-dimensional structure of the antibody and the topology of the CDR loops (Chothia et al. (1989) Nature 342: 877-883, Al-Lazikani et al., “Standard conformations for the canonical structures of immunoglobulins”, Journal of Molecular Biology, 273, 927-948 (1997)), Kabat based on the variability of the antibody sequence (Kabat et al., Sequences of Proteins of Immunological Interest, 4th Ed., U.S. Department of Health and Human Services, National Institutes of Health (1987)), AbM (University of Bath), Contact (University College London), the international ImMunoGeneTics database (IMGT) (World Wide Web at imgt.cines.fr / ), and North CDR definition based on affinity propagation clustering using a large number of crystal structures. It will be understood by those skilled in the art that, unless otherwise specified, the terms “CDR” and “complementarity determining region” of a given antibody or region thereof (e.g., a variable region) are to be understood as encompassing complementarity determining regions as defined by any of the above known schemes described by the present application. While the scope of the present application is based on the sequences shown according to the Kabat definition, the amino acid sequences corresponding to the CDRs according to other CDR definitions should also fall within the scope of the present application.

[0083] The term "antigen-binding fragment" refers to one or more fragments of an antibody that retain the ability to specifically bind to an antigen. It has been shown that the antigen- binding function of an antibody can be performed by fragments of a full-length antibody. Examples of binding fragments encompassed within the term "antigen-binding fragment" include (i) a Fab fragment, a monovalent fragment consisting of the VL, VH, CL, and CHI domains; (ii) a F(ab')2 fragment, a bivalent fragment comprising two Fab fragments linked by a disulfide bridge at the hinge region; (iii) a Fd fragment consisting of the VH and CHI domains; (iv) a Fv fragment consisting of the VH and VL domains of a single arm of an antibody; (v) a single domain or dAb fragment (Ward et al., (1989) Nature 341 :544-546), which consists of a VH domain; and (vi) an isolated complementarity determining region (CDR) or (vii) a combination of two or more isolated CDRs, which can optionally be joined by a synthetic linker.

[0084] The term "drug loading" refers to the average number of cytotoxic drugs loaded on each ligand of the molecule of Formula (I), which can also be expressed as the ratio of the amount of drug to the amount of antibody, and the drug loading can range from 0 to 12, preferably 1 to 10, cytotoxic drugs (D) per antibody (Pc). In embodiments of the disclosure, the drug loading is expressed as n, which can also be referred to as the DAR value, and exemplary values are 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, on average. The average number of drugs per ADC molecule can be identified using routine methods such as UV / visible spectroscopy, mass spectrometry, ELISA assays, and HPLC profiles following conjugation reactions.

[0085] The terms "administering" and "treatment" when applied to an animal, human, test subject, cell, tissue, organ, or biological fluid, refer to the contact of an exogenous drug, therapeutic agent, diagnostic agent, or composition with the animal, human, test subject, cell, tissue, organ, or biological fluid. "Administering" and "treatment" can refer, for example, to therapeutic, pharmacokinetic, diagnostic, research, and experimental methods. Treatment of a cell includes contact of the agent with the cell, as well as contact of the agent with a fluid that is in contact with the cell. "Administering" and "treatment" also mean in vitro and ex vivo treatment of a cell by an agent, diagnostic, binding composition, or by another cell. "Treatment" when applied to a human, veterinary, or research subject, refers to therapeutic treatment, prophylactic or preventative measures, research, and diagnostic applications.

[0086] The term "treatment" means the administration of an internal or external therapeutic agent, such as a composition comprising any of the binding compounds of the disclosure, to a patient having one or more symptoms of a disease, where the therapeutic agent is known to have a therapeutic effect on those symptoms. Typically, the therapeutic agent is administered in an amount effective to alleviate one or more symptoms of the disease in the treated patient or population, to induce regression of such symptoms or to inhibit the progression of such symptoms to any clinically measurable extent. The amount of therapeutic agent effective to alleviate any particular symptom of a disease (also referred to as "therapeutically effective amount") can vary according to factors such as the disease state, age, and weight of the patient, and the ability of the drug to elicit a desired effect in the patient. Whether a disease symptom has been alleviated can be assessed by any clinical detection method typically used by a physician or other health care professional to assess the severity or progression of the symptom. While embodiments of the disclosure (e.g., methods of treatment or articles of manufacture) can not be effective in alleviating every symptom of a targeted disease, it is determined that a statistically significant number of patients should have a targeted disease symptom alleviated according to any statistical test known in the art, such as the Student's t-test, the chi-square test, the U-test according to Mann and Whitney, the Kruskal-Wallis test (H-test), the Jonckheere-Terpstra test, and the Wilcoxon test.

[0087] The term "effective amount" includes an amount which is sufficient to ameliorate or prevent the symptoms or conditions of a medical disease. An effective amount also means an amount which is sufficient to allow or facilitate diagnosis. The effective amount for a particular patient or veterinary subject can vary depending on such factors as the condition to be treated, the overall health status of the patient, the method route and dose of administration, and the severity of side effects. An effective amount can be the maximum dose or dosing regimen that avoids significant side effects or toxic effects.

[0088] The antibody drug conjugates of the present application can be administered by any suitable means, including parenterally, intrapulmonary, and intranasally, and if desired for local treatment, intralesionally. Parenteral infusions include intramuscular, intravenous, intraarterial, intraperitoneal, or subcutaneous administration. The administration can be by any suitable route, for example by injection, for example intravenous or subcutaneous injection, depending in part on whether the administration is short term or long term. A variety of dosing regimens are contemplated herein, including but not limited to a single administration or multiple administrations at different time points, bolus administration, and pulsed infusion.

[0089] The antibody drug conjugates of the application can be formulated, dosed, and administered in a fashion consistent with good medical practice. Factors for consideration in this context include the particular disorder being treated, the particular mammal being treated, the clinical condition of the individual patient, the cause of the disorder, the site of delivery of the agent, the method of administration, the scheduling of administration, and other factors known to medical practitioners. The antibody drug conjugates need not be, but are optionally formulated with one or more agents currently used in the prevention or treatment of the disorder in question. The effective amount of such other agents depends on the amount of antibody drug conjugate present in the formulation, the type of disorder or treatment, and other factors discussed above. These are generally used in the same dosages and with administration routes and schedules as are used in connection with the treatment of the disorder in question.

[0090] For the prevention or treatment of disease, the appropriate dosage of an antibody drug conjugate of the application will depend on the type of disease to be treated, the type of antibody, the severity and course of the disease, whether the antibody is for preventive or therapeutic purposes, previous therapy, the patient's clinical history and response to the antibody, and the judgment of the treating physician. The antibody drug conjugate is suitably administered to the patient at one time or over a series of treatments. Depending on the type and severity of the disease, about 1 μg / kg to 100 mg / kg of antibody can be an initial candidate dosage, whether by one or more divided doses administered by injection, or by continuous infusion. BRIEF DESCRIPTION OF DRAWINGS

[0091] Figure 1: Clinical study flow chart of Example 3

[0092] Figure 2: Clinical study flow chart of Example 4 DETAILED DESCRIPTION

[0093] The application will be explained in greater detail in connection with the embodiments below, which are only used to illustrate the technical solutions of the application, and are not intended to limit the essence and scope of the application.

[0094] Example 1. Preparation of anti-B7H3 antibody drug conjugates

[0095] According to the production method described in WO2020063673, h1702DS (anti-B7H3 antibody) was used to prepare anti-B7H3 antibody-drug conjugates with the structure shown below, and the average value of the HIC method was calculated: n = 4.1, that is, FADC-2. Among them, the sequence of the heavy chain of h1702DS is shown as SEQ ID NO: 09, and the sequence of the light chain is shown as SEQ ID NO: 10.

[0096] The sequences of the heavy and light chains of h1702DS are as follows:

[0097] Heavy chain (IgG1) amino acid sequence: (SEQ ID NO: 09)

[0098] Light chain (lambda) amino acid sequence: (SEQ ID NO: 10)

[0099] Example 2. Anti-B7H3 antibody drug conjugate mouse in vivo pharmacodynamic study

[0100] Anti-B7H3 antibody drug conjugate has shown strong anti-tumor activity against small cell lung cancer in preclinical, with good safety.

[0101] In the human small cell lung cancer cell line NCI-H146 xenograft tumor model, the TGI of anti-B7H3 antibody naked antibody at 8 mg / kg dose was 5.70%. Anti-B7H3 antibody drug conjugate at 2, 4, 8 mg / kg dose, TGI was 73.31%, 99.86% and 177.61% respectively, the tumor inhibition effect was significant (p value was p=0.002, p<0.001 and p<0.001 respectively) and showed a good dose-effect relationship, and 2 animals (2 / 6) showed tumor regression at 4 mg / kg dose, and all animals (6 / 6) showed tumor regression at 8 mg / kg dose, and all animals tolerated well.

[0102] In addition, for In the human small cell lung cancer subcutaneous xenograft tumor model, anti-B7H3 antibody drug conjugate at 5 mg / kg dose, single administration, had significant tumor inhibition effect on LU5217, LU5233, LU2514, LU5159, LU11953, LU5180 and LU5243 tumor-bearing animal models, and the corresponding TGI was 98.19%, 99.42%, 148.01%, 168.04%, 195.62%, 200.00% and 200.00% respectively.

[0103] Example 3. Phase I clinical study of anti-B7H3 antibody drug conjugate for injection in patients with advanced solid tumors

[0104] 1. Test drug

[0105] Anti-B7H3 antibody drug conjugate, dosage form: injection (lyophilized powder), specification: 100 mg / bottle, packaged with 20 mL of borosilicate glass tube injection bottle. Route of administration: intravenous infusion. Storage conditions: 2-8°C, sealed and light-protected, avoid freezing or shaking.

[0106] The research drugs used in this test were provided by Shanghai Hansoh Biomedical Technology Co., Ltd.

[0107] 2. Enrolled subjects

[0108] Male or female, 18 years of age or older.

[0109] Diagnosis of tumor and history of prior anti-treatment:

[0110] Stage Ia: Pathologically confirmed advanced solid tumor (need to provide key immunohistochemistry / tumor cell phenotype results required for clear diagnosis), failed standard treatment or intolerance to standard treatment.

[0111] Stage Ib: Pathologically confirmed advanced solid tumor (need to provide key immunohistochemistry / tumor cell phenotype results required for clear diagnosis), with the following specific requirements:

[0112] • Cohort 1: Progression or intolerance after at least one line of treatment of non-small cell lung cancer without clear driver genes, locally advanced or metastatic, at least including platinum-containing chemotherapy in the past treatment of tumor advanced stage, the total number of treatment lines is not more than 3 lines;

[0113] • Cohort 2: Progression or intolerance after at least one line of treatment of extensive stage small cell lung cancer, the total number of treatment lines is not more than 3 lines;

[0114] • Cohort 3: Progression or intolerance after standard treatment of non-small cell lung cancer with known EGFR mutation or other driver gene positive, locally advanced or metastatic:

[0115] - Known driver genes include: EGFR mutation, ALK, KRAS, ROS1, BRAF, NTRK1 / 2 / 3, HER-2 mutation, MET exon 14 skipping and amplification, RET fusion / mutation; actual research process in real time update according to local clinical practice guidelines.

[0116] • Cohort 4: Other advanced solid tumors other than cohorts 1-3, which have no standard treatment or have failed standard treatment or intolerance to standard treatment.

[0117] According to RECIST 1.1, the subject has at least 1 target lesion. The requirements for target lesions are: measurable lesions that have not been treated locally such as irradiation, or have been clearly progressed after local treatment, the longest diameter at baseline is ≥10mm (if it is lymph node, the maximum short diameter is required to be ≥15mm). Brain lesions alone are not accepted as target lesions.

[0118] ECOG PS score is 0-1 and there is no deterioration within 2 weeks before the first administration.

[0119] Minimum expected survival is greater than 12 weeks.

[0120] Voluntarily participate in this clinical trial, understand the research procedures and can sign the informed consent in writing.

[0121] 3. Method of administration

[0122] All subjects in this study will be administered intravenous infusion continuously, once every 3 weeks (Q3W), 21 days as a treatment cycle, and continuously administered until objective disease progression (except for withdrawal) or reaching other standards of terminating study treatment as stipulated in the scheme.

[0123] Intravenous infusion administration, the first intravenous infusion lasts at least 90 min (including pipe flushing stage). Each subsequent infusion can be adjusted according to the tolerance of the subject, but should not be less than 30 min (including pipe flushing stage).

[0124] Phase Ia

[0125] The subjects who pass the screening are administered anti-B7H3 antibody drug conjugates, once every 3 weeks, and according to the body weight of the subject before each administration, the calculation starts from the lowest preset dose of 1.0 mg / kg, and the preset dose groups are 1.0 mg / kg, 2.0 mg / kg, 4.0 mg / kg, 6.0 mg / kg, 8.0 mg / kg, 10.0 mg / kg, 12.0 mg / kg, 16.0 mg / kg, and so on, in ascending order, and the administration mode is intravenous infusion.

[0126] Phase Ib:

[0127] Queue 1: All subjects are randomly assigned to the 8.0 mg / kg and 10.0 mg / kg dose groups according to a ratio of 1:1 to receive study treatment.

[0128] Queue 2: All subjects are randomly assigned to the 8.0 mg / kg and 10.0 mg / kg dose groups according to a ratio of 1:1 to receive study treatment.

[0129] Queue 3: All subjects will receive study treatment at a dose of 10.0 mg / kg.

[0130] Queue 4: All subjects are originally planned to receive study treatment at a dose of 10.0 mg / kg; based on the evaluation, the study treatment at a dose of 8.0 mg / kg is added to the original plan.

[0131] If the optimal target recommended dose has been determined based on the existing phase data at any stage of the study, based on the principles of science and subject benefit, the applicant will, in accordance with the agreement with the study, directly transfer the subjects in other dose groups to use the target recommended dose for enrollment and / or administration.

[0132] 4. Test results

[0133] The study showed that, as of November 30, 2023, a total of 63 patients with recurrent small cell lung cancer were enrolled, and the ORR in the 8.0 mg / kg dose group was 58.1% (18 / 31, of which 15 were confirmed). The ORR of the existing standard treatment topotecan is about 7%-27%. The anti-tumor effect of the anti-B7H3 antibody drug conjugate on recurrent small cell lung cancer is better than the existing standard treatment, and the safety data shows that the anti-B7H3 antibody drug conjugate is safe and well tolerated in the 8.0 mg / kg dose group.

[0134] As of January 20, 2025, a total of 65 patients with extensive stage small cell lung cancer who had received at least one line of treatment were enrolled, of which 43 received 8.0 mg / kg treatment and 22 received 10.0 mg / kg treatment.

[0135] The effectiveness results are shown in Table 1. In the combined extensive stage small cell lung cancer population (total n=65, combined two dose groups), the cORR was 52.3%, and the DCR was 87.7%. The median progression-free survival was 6.2 months, and the median overall survival was 13.0 months, and an exact anti-tumor effect was observed.

[0136] Table 1. Effectiveness data of anti-B7H3 antibody drug conjugate in the treatment of extensive stage small cell lung cancer patients who have received at least one line of treatment

[0137] Among them, the efficacy study in the platinum-sensitive and platinum-resistant subtypes of extensive stage small cell lung cancer showed a wider treatment potential, and the cORR of platinum-sensitive patients and platinum-resistant patients was 78.6% and 57.1%, respectively, and the OS was 17.1 months and 14.9 months, respectively. See Table 2 for details.

[0138] Table 2. Effectiveness data of anti-B7H3 antibody drug conjugate in the treatment of each subtype of extensive stage small cell lung cancer

[0139] The most common hematologic treatment-related adverse reactions TRAEs in the 8 mg / kg and 10 mg / kg arms in the pooled population of extensive-stage small cell lung cancer patients who had received at least one prior line of therapy included anemia (93.2% and 80.0%), decreased white blood cell count (75% and 88%), decreased neutrophil count (59.1% and 84.0%), and decreased platelet count (50.0% and 56.0%). In the pooled population of extensive-stage small cell lung cancer patients, the common non-hematologic treatment-related adverse reactions TRAEs included nausea (53.6%), decreased appetite (49.3%), fever (46.4%), fatigue (43.5%), vomiting (43.5%), and hypoalbuminemia (37.7%). These treatment-related adverse reactions can be controlled and managed with appropriate prophylaxis and / or symptomatic support measures, and the overall safety profile is manageable and predictable.

[0140] As of January 20, 2025, a total of 152 patients with non-small cell lung cancer were enrolled, and the exact anti-tumor effect was observed, with a cORR of 22.4% and a DCR of 80.9%. The median progression-free survival was 5.5 months, and the median overall survival was 13.7 months. A total of 84 patients received 8.0 mg / kg treatment, with a cORR of 23.8% and a DCR of 83.3%. The median progression-free survival was 4.4 months, and the median overall survival was 13.4 months.

[0141] The non-small cell lung cancer subtype analysis showed that in 67 patients with driver gene-negative non-squamous non-small cell lung cancer, the cORR was 23.9%, the DCR was 76.1%, the median PFS was 5.6 months, and the median overall survival was higher than 9.3 months. Among them, 39 patients with driver gene-negative non-squamous non-small cell lung cancer received 8.0 mg / kg treatment, with a cORR of 33.3%, a DCR of 82.1%, a median PFS of 7.0 months, and a median overall survival of more than 10.5 months. The exact anti-tumor effect was observed.

[0142] Table 3. Anti-B7H3 antibody drug conjugate treatment of non-small cell lung cancer effectiveness data

[0143] In the non-small cell lung cancer cohort, the most common treatment-related adverse events TRAEs in the 8 mg / kg and 10 mg / kg cohorts at both dose levels included anemia (75.3% and 78.4%), decreased white blood cell count (69.9% and 77.0%), decreased neutrophil count (65.6% and 71.6%), and decreased platelet count (21.5% and 45.9%). Non-hematologic treatment-related adverse events TRAEs in the total non-small cell lung cancer population included, for example, fever (48.5%), decreased appetite (43.1%), nausea (41.3%), hypoalbuminemia (38.3%), fatigue (32.3%), and vomiting (32.9%). These treatment-related adverse events can be controlled and managed with appropriate prophylaxis and / or symptomatic support measures, and the overall safety profile is manageable and predictable.

[0144] In summary, the anti-B7H3 antibody drug conjugate showed a manageable safety profile and encouraging antitumor activity in patients with small cell lung cancer and non-small cell lung cancer.

[0145] Example 4. Clinical study of anti-B7H3 antibody drug conjugate for consolidation treatment after chemoradiotherapy for limited-stage small cell lung cancer

[0146] 1. Overall study design

[0147] This is a randomized, controlled, open-label, multicenter phase III clinical study to evaluate the efficacy and safety of anti-B7H3 antibody drug conjugate versus observation for consolidation treatment in subjects with limited-stage small cell lung cancer (LS-SCLC) who have not progressed after chemoradiotherapy (CRT), and the study flow chart is shown in Figure 1.

[0148] 2. Test drug

[0149] Anti-B7H3 antibody drug conjugate for injection, dosage form: injection (lyophilized powder), specification: 100 mg / bottle.

[0150] 3. Enrolled subjects

[0151] Patients with limited-stage small cell lung cancer who have not progressed after chemoradiotherapy.

[0152] 4. Method of administration

[0153] All subjects in the trial group will receive anti-B7H3 antibody drug conjugate continuously, and the dose is 8.0 mg / kg. The administration frequency is once every 3 weeks (21 days) (Q3W), and the administration is continued until objective disease progression (except for continued administration after progression) or other criteria for termination of study treatment as specified in the protocol are met.

[0154] While the specific embodiments of the application have been described in detail, those skilled in the art will appreciate that various modifications and alterations to the details can be made within the scope of the application as disclosed in the teachings of the present application. The entire disclosure of the application is set out in the accompanying claims and any equivalents thereof.

Claims

1. The use of antibody-drug conjugates in the preparation of drugs for treating lung cancer, wherein the structure of the antibody-drug conjugate is shown in formula (I): wherein: n is 1 to 10, preferably 2 to 8, more preferably 3 to 8, n is a decimal or an integer; Pc is an anti-B7H3 antibody or an antigen-binding fragment thereof.

2. The use according to claim 1, wherein the anti-B7H3 antibody or an antigen-binding fragment thereof comprises heavy chain HCDR1, HCDR2, HCDR3 as shown in the amino acid sequences of SEQ ID NO: 01, 02 and 03, respectively, and light chain LCDR1, LCDR2 and LCDR3 as shown in the amino acid sequences of SEQ ID NO: 04, 05 and 06, respectively.

3. The use according to claim 1 or 2, wherein the anti-B7H3 antibody or an antigen-binding fragment thereof is selected from a humanized antibody or a fragment thereof.

4. The use according to claim 3, wherein the anti-B7H3 antibody or an antigen-binding fragment thereof comprises a heavy chain constant region of human IgG1, IgG2, IgG3 or IgG4 isotype, and a light chain constant region comprising kappa or lambda; preferably, the anti-B7H3 antibody or an antigen-binding fragment thereof comprises a heavy chain constant region of IgG1 or IgG4 isotype.

5. The use according to claim 3, wherein the heavy chain variable region sequence of the anti-B7H3 antibody or an antigen-binding fragment thereof is a sequence as shown in SEQ ID NO: 07 or a variant thereof, and the light chain variable region sequence is a sequence as shown in SEQ ID NO: 08 or a variant thereof; preferably, the heavy chain variable region sequence is a sequence as shown in SEQ ID NO: 07, and the light chain variable region sequence is a sequence as shown in SEQ ID NO:

08.

6. The use according to any one of claims 1 to 5, wherein the heavy chain sequence of the anti-B7H3 antibody or an antigen-binding fragment thereof is a sequence as shown in SEQ ID NO: 09 or a variant thereof, and the light chain sequence is a sequence as shown in SEQ ID NO: 10 or a variant thereof; preferably, the heavy chain sequence is a sequence as shown in SEQ ID NO: 09, and the light chain sequence is a sequence as shown in SEQ ID NO:

10.

7. The use according to any one of claims 1 to 6, wherein the antibody drug conjugate is administered at a frequency of once a week, once every two weeks, once every three weeks, once every four weeks, once a month, or once every three to six months; preferably, once every two weeks, once every three weeks, or once every four weeks; more preferably, once every three weeks.

8. The use according to any one of claims 1 to 7, wherein the antibody drug conjugate is administered at a dose of 0.1 mg / kg to 20 mg / kg, preferably 0.5 mg / kg to 18 mg / kg, more preferably 1 mg / kg to 16 mg / kg, further preferably 4 mg / kg to 12 mg / kg.

9. The use of claim 8, wherein the dose of the antibody drug conjugate is selected from 4.0 mg / kg, 4.1 mg / kg, 4.2 mg / kg, 4.3 mg / kg, 4.4 mg / kg, 4.5 mg / kg, 4.6 mg / kg, 4.7 mg / kg, 4.8 mg / kg, 4.9 mg / kg, 5 mg / kg, 5.1 mg / kg, 5.2 mg / kg, 5.3 mg / kg, 5.4 mg / kg, 5.5 mg / kg, 5.6 mg / kg, 5.7 mg / kg, 5.8 mg / kg, 5.9 mg / kg, 6.0 mg / kg, 6.1 mg / kg, 6.2 mg / kg, 6.3 mg / kg, 6.4 mg / kg, 6.5 mg / kg, 6.6 mg / kg, 6.7 mg / kg, 6.8 mg / kg, 6.9 mg / kg, 7 mg / kg, 7.1 mg / kg, 7.2 mg / kg, 7.3 mg / kg, 7.4 mg / kg, 7.5 mg / kg, 7.6 mg / kg, 7.7 mg / kg, 7.8 mg / kg, 7.9 mg / kg, 8 mg / kg, 8.1 mg / kg, 8.2 mg / kg, 8.3 mg / kg, 8.4 mg / kg, 8.5 mg / kg, 8.6 mg / kg, 8.7 mg / kg, 8.8 mg / kg, 8.9 mg / kg, 9 mg / kg, 9.1 mg / kg, 9.2 mg / kg, 9.3 mg / kg, 9.4 mg / kg, 9.5 mg / kg, 9.6 mg / kg, 9.7 mg / kg, 9.8 mg / kg, 9.9 mg / kg, 10 mg / kg, 10.1 mg / kg, 10.2 mg / kg, 10.3 mg / kg, 10.4 mg / kg, 10.5 mg / kg, 10.6 mg / kg, 10.7 mg / kg, 10.8 mg / kg, 10.9 mg / kg, 11 mg / kg, 11.1 mg / kg, 11.2 mg / kg, 11.3 mg / kg, 11.4 mg / kg, 11.5 mg / kg, 11.6 mg / kg, 11.7 mg / kg, 11.8 mg / kg, 11.9 mg / kg, or 12 mg / kg. Preferably, the dose of the antibody drug conjugate is selected from 4.0 mg / kg, 6.0 mg / kg, 8.0 mg / kg, 10.0 mg / kg, 12.0 mg / kg.

10. The use of any one of claims 7-9, wherein the antibody drug conjugate is administered intravenously at a dose of 4 mg / kg to 12 mg / kg once every two weeks, once every three weeks, or once every four weeks. Preferably, the antibody drug conjugate is administered intravenously at a dose of 4.0 mg / kg, 6.0 mg / kg, 8.0 mg / kg, 10.0 mg / kg, 12.0 mg / kg once every three weeks.

11. The use according to any one of claims 1 to 10, wherein the lung cancer is selected from the group consisting of small cell lung cancer, non-small cell lung cancer, lung squamous cell carcinoma, lung adenocarcinoma, large cell lung cancer; Preferably, the lung cancer is selected from the group consisting of limited stage small cell lung cancer, extensive stage small cell lung cancer, non-small cell lung squamous carcinoma, non-small cell lung adenocarcinoma, non-squamous non-small cell lung cancer.

12. The use according to claim 11, wherein the non-small cell lung cancer is locally advanced or metastatic non-small cell lung cancer; preferably locally advanced or metastatic non-small cell lung cancer that progressed or was intolerant to standard treatment, or locally advanced or metastatic non-small cell lung cancer that progressed or was intolerant to at least one line of treatment.

13. The use according to claim 12, wherein the non-small cell lung cancer is locally advanced or metastatic non-small cell lung cancer that progressed or was intolerant to at least one line of treatment, or locally advanced or metastatic non-small cell lung cancer that progressed or was intolerant to standard treatment, known to have EGFR mutation or other driver gene positive, preferably locally advanced or metastatic non-squamous non-small cell lung cancer that progressed or was intolerant to at least one line of treatment, or locally advanced or metastatic non-squamous non-small cell lung cancer that progressed or was intolerant to standard treatment, known to have EGFR mutation or other driver gene positive.

14. The use of claim 13, wherein the driver genes comprise: EGFR mutation, ALK, KRAS, ROS1, BRAF, NTRK1 / 2 / 3, HER-2 mutation, MET exon 14 skipping and amplification, RET fusion / mutation.

15. The use according to claim 11, wherein the small cell lung cancer is extensive stage small cell lung cancer that progressed or was intolerant to at least one line of treatment.

16. The use according to claim 11, wherein the small cell lung cancer is limited stage small cell lung cancer; preferably the small cell lung cancer is limited stage small cell lung cancer that did not progress after receiving chemoradiation (CRT).

17. The use according to claim 16, wherein the type of chemoradiation comprises concurrent chemoradiation (cCRT) and sequential chemoradiation (sCRT).

18. The use according to claim 16, wherein the chemotherapeutic drug of the chemoradiation is selected from the group consisting of cisplatin / carboplatin in combination with etoposide, and the frequency of radiotherapy of the chemoradiation is once a day or twice a day, and the total dose of radiotherapy received is 66 Gy (±10%) or 45 Gy (±10%).

19. The use according to any one of claims 1 to 18, wherein the evaluation of the therapeutic effect comprises detecting the concentration of a biomarker in a patient sample, preferably the biomarker comprises soluble B7-H3.

20. The method according to claim 19, wherein the relationship between the biomarker and the effectiveness of the antibody drug conjugate is evaluated by detecting the concentration of soluble B7-H3 in a patient blood sample collected at the screening period, during the treatment, and at the end of treatment visit.

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