A Study of BL-B01D1 Combined With Glecirasib in Patients With KRAS G12C-Mutated Locally Advanced or Metastatic Non-Small Cell Lung Cancer

Inclusion Criteria:

1. Voluntarily sign the informed consent form and comply with protocol requirements;
2. No restriction on gender;
3. Age ≥18 years and ≤75 years;
4. Expected survival time ≥3 months;
5. Patients with locally advanced or metastatic non-small cell lung cancer;
6. Agree to provide archived tumor tissue specimens from the primary or metastatic lesion within 2 years, or fresh tissue samples;
7. Must have at least one measurable lesion as defined by RECIST v1.1;
8. ECOG performance status score ≤1;
9. Toxicity from prior antitumor therapy has recovered to ≤Grade 1 as defined by NCI-CTCAE v6.0;
10. No severe cardiac dysfunction, with left ventricular ejection fraction ≥50%;
11. Organ function levels must meet the requirements;
12. Coagulation function: international normalized ratio ≤1.5, and activated partial thromboplastin time ≤1.5×ULN;
13. Urine protein ≤1+ or <1000 mg/24 h;
14. For premenopausal women of childbearing potential, a pregnancy test must be performed within 7 days before starting treatment; serum pregnancy testing must exclude pregnancy, and the patient must be non-lactating; all enrolled patients (regardless of male or female) should use adequate barrier contraception throughout the entire treatment period and for 7 months after treatment completion.

Exclusion Criteria:

1. Prior treatment with drugs targeting KRAS G12C;
2. Prior use of ADC drugs with small-molecule toxins as topoisomerase I inhibitors;
3. Coexisting other known oncogenic driver gene mutations that can be targeted therapeutically;
4. Prior history of intestinal disease or major gastric surgery;
5. Participation in any other clinical trial within 4 weeks before the first administration of this trial;
6. History of severe heart disease or cerebrovascular disease;
7. Receipt of radical radiotherapy, major surgery, extensive radiotherapy, etc., within 4 weeks before randomization in the study;
8. Unstable thrombotic events requiring therapeutic intervention within 6 months before screening;
9. QTc interval prolongation, complete left bundle branch block, third-degree atrioventricular block, frequent and uncontrollable arrhythmias;
10. History of interstitial lung disease/interstitial pneumonia treated with steroids, etc.;
11. Concurrent pulmonary disease leading to clinically severe impairment of respiratory function;
12. Severe infection occurring within 4 weeks before randomization in the study;
13. Patients at risk of active autoimmune disease, or patients with a history of autoimmune disease;
14. Diagnosis of active malignancy within 5 years before randomization in the study;
15. Positive human immunodeficiency virus antibody, active tuberculosis, active syphilis, active hepatitis B virus infection, or hepatitis C virus infection;
16. Hypertension poorly controlled with two antihypertensive drugs;
17. Patients with poorly controlled blood glucose;
18. Presence of a large amount of serous cavity effusion, or serous cavity effusion with obvious symptoms caused by the serous cavity effusion, etc.;
19. Active central nervous system metastasis;
20. Imaging examination suggesting that the tumor has invaded or encased the abdomen, chest, etc.;
21. Severe and unhealed wounds, ulcers, or fractures within 4 weeks before signing informed consent;
22. Trial participants with clinically obvious bleeding or a clear bleeding tendency within 4 weeks before signing informed consent;
23. History of allogeneic stem cell, bone marrow, or organ transplantation;
24. Patients with a history of allergy to recombinant humanized antibodies or allergy to any excipient component of BL-B01D1;
25. History of severe neurological or psychiatric disease;
26. History of autologous or allogeneic stem cell transplantation;
27. Pregnant or breastfeeding women;
28. Trial participants planning to receive vaccination or who received a live vaccine within 28 days before randomization in the study;
29. Other circumstances in which the investigator considers it inappropriate to participate in this clinical trial.