Two-Drug combo targets stubborn KRAS lung cancer

Copied word for word from the study's registry entry, so the wording is the study team's rather than ours.

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.