Overview

This trial is a registrational Phase III, randomized, open-label, multicenter study to evaluate the efficacy and safety of BL-B01D1 in combination with osimertinib in patients with unresectable EGFR-mutated Stage III non-small cell lung cancer who have not progressed following platinum-based chemoradiotherapy.

Eligibility

Inclusion Criteria:

1. Voluntarily sign the informed consent form and comply with the protocol requirements;
2. Age ≥ 18 years and ≤ 75 years, regardless of gender;
3. Expected survival time ≥ 3 months;
4. Unresectable Stage III non-small cell lung cancer;
5. Detection of one of the EGFR-sensitive mutation types in tumor tissue;
6. Agree to provide archived primary tumor tissue specimens or fresh tissue samples within 1 year;
7. In platinum-based radical chemoradiotherapy, the platinum-containing chemotherapy regimen must include one of the specified drugs in addition to the platinum agent;
8. In platinum-based radical chemoradiotherapy, patients must have received a total radiation dose of 60 Gy ± 10% before randomization;
9. Toxicities from prior chemoradiotherapy must have resolved to ≤ Grade 1 as defined by NCI-CTCAE v6.0;
10. ECOG performance status score of 0 or 1;
11. No severe cardiac dysfunction, with left ventricular ejection fraction ≥ 50%;
12. Organ function levels must meet the requirements;
13. Urine protein ≤ 1+ or \< 1000 mg/24h;
14. For premenopausal women with childbearing potential, a serum pregnancy test must be performed within 7 days before starting treatment, and the test must rule out pregnancy; they must not be lactating; all enrolled trial participants must take adequate barrier contraceptive measures throughout the treatment period and for 7 months after treatment ends.

Exclusion Criteria:

1. SCLC, mixed SCLC and NSCLC, or other non-NSCLC pathological types;
2. The trial participant has received other chemotherapy, radiotherapy, etc., for NSCLC apart from radical chemoradiotherapy;
3. Major surgery within 4 weeks prior to the first dose;
4. Prior treatment with ADC drugs using topoisomerase I inhibitors as toxins, or antibodies/ADCs targeting EGFR and/or HER3;
5. History of severe heart disease or cerebrovascular disease;
6. Prolonged QTc interval, complete left bundle branch block, second- or third-degree atrioventricular block, or frequent and uncontrolled arrhythmias;
7. Any thrombotic events such as deep vein thrombosis, arterial thrombosis, or pulmonary embolism within 6 months prior to screening;
8. Diagnosis of active malignancy within 5 years prior to study randomization;
9. Hypertension poorly controlled by two antihypertensive medications;
10. Trial participants with poorly controlled blood glucose levels;
11. Current radiation pneumonitis of Grade ≥2 as defined by CTCAE;
12. Concurrent lung disease resulting in clinically severe respiratory impairment;
13. Severe infection within 4 weeks prior to study randomization;
14. Large serous cavity effusions or symptomatic serous cavity effusions;
15. Imaging findings suggesting tumor invasion or encasement of major blood vessels in the abdomen, chest, neck, or pharynx;
16. Severe non-healing wounds, ulcers, or fractures within 4 weeks prior to signing informed consent;
17. Trial participants with clinically significant bleeding or a clear tendency for bleeding within 4 weeks prior to signing informed consent;
18. Trial participants with a history of inflammatory bowel disease, extensive bowel resection, or immune-mediated enteritis;
19. History of allergy to recombinant humanized antibodies or chimeric human-mouse antibodies, or allergy to any excipient components of the investigational drug;
20. History of autologous or allogeneic stem cell transplantation;
21. Positive for human immunodeficiency virus antibodies, active hepatitis B virus infection, or hepatitis C virus infection;
22. History of severe neurological or psychiatric disorders, or a history of substance abuse, alcoholism, or drug addiction;
23. Trial participants planning to receive or having received live vaccines within 28 days prior to study randomization;
24. Other conditions deemed by the investigator as unsuitable for participation in this clinical trial due to complications or other reasons.