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

• Voluntarily sign the informed consent form and comply with protocol requirements;
• No restriction on gender;
• Age ≥18 years and ≤75 years;
• Expected survival time ≥3 months;
• Patients with locally advanced or metastatic non-small cell lung cancer;
• Agree to provide archived tumor tissue specimens from the primary or metastatic lesion within 2 years, or fresh tissue samples;
• Must have at least one measurable lesion as defined by RECIST v1.1;
• ECOG performance status score ≤1;
• Toxicity from prior antitumor therapy has recovered to ≤Grade 1 as defined by NCI-CTCAE v6.0;
• No severe cardiac dysfunction, with left ventricular ejection fraction ≥50%;
• Organ function levels must meet the requirements;
• Coagulation function: international normalized ratio ≤1.5, and activated partial thromboplastin time ≤1.5×ULN;
• Urine protein ≤1+ or <1000 mg/24 h;
• 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

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