Clinical trial NCT06838273: A Study of BL-B01D1 in Combination With Osimertinib Versus Osimertinib as First-Line Treatment in Patients With EGFR-Mutated Locally Advanced or Metastatic Non-Small Cell Lung Cancer
Official title: A Phase III Randomized Study of BL-B01D1 in Combination With Osimertinib Versus Osimertinib as First-Line Treatment in Patients With EGFR-Mutated Locally Advanced or Metastatic Non-Small Cell Lung Cancer
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Non-small Cell Lung Cancer
Lead sponsor: Sichuan Baili Pharmaceutical Co., Ltd.
Sponsor class: INDUSTRY
Collaborators: name: Baili-Bio (Chengdu) Pharmaceutical Co., Ltd.
First posted: 2025-02-20
Enrollment: 696
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This trial is a registered phase III, randomized, open-label, multicenter study to evaluate the efficacy and safety of BL-B01D1 in combination with osimertinib versus osimertinib as first-Line treatment in patients with EGFR-mutated locally advanced or metastatic Non-small Cell Lung Cancer.


Eligibility criteria: Inclusion Criteria:

1. Sign the informed consent form voluntarily and follow the protocol requirements;
2. Age ≥18 years old;
3. Expected survival time ≥3 months;
4. Patients with unresectable or radical radiotherapy for locally advanced non-small cell lung cancer;
5. Documentation of EGFR sensitive mutations detected from tumor tissue or blood samples;
6. Consent to provide archived tumor tissue samples or fresh tissue samples of primary or metastatic lesions at or after diagnosis for testing, including EGFR mutation type;
7. At least one measurable lesion meeting the RECIST v1.1 definition was required;
8. ECOG 0 or 1;
9. The toxicity of previous antineoplastic therapy has returned to ≤ grade 1 as defined by NCI-CTCAE v5.0;
10. No severe cardiac dysfunction, left ventricular ejection fraction ≥50%;
11. The organ function level must meet the requirements on the premise that blood transfusion and colony-stimulating factor are not allowed within 14 days before the screening period;
12. Urinary protein ≤2+ or \< 1000mg/24h;
13. For premenopausal women of childbearing potential, a pregnancy test must be performed within 7 days before the initiation of treatment, serum pregnancy must be negative, and the patient must not be lactating; All enrolled patients (male or female) were advised to use adequate barrier contraception throughout the treatment cycle and for 6 months after the end of treatment.

Exclusion Criteria:

1. Previous histologic or cytological evidence of small cell or mixed small/non-small cell components;
2. Patients with previous systemic therapy;
3. Patients had received EGFR-TKI therapy;
4. Studies received radical radiotherapy, major surgery, and large area radiotherapy within 4 weeks before randomization;
5. History of severe heart disease and cerebrovascular disease;
6. Unstable thrombotic events requiring therapeutic intervention within 6 months before screening; Infusion-related thrombosis was excluded;
7. QT prolongation, complete left bundle branch block, III degree atrioventricular block, frequent and uncontrollable arrhythmia;
8. Were diagnosed with active malignancy within 3 years before randomization;
9. Hypertension poorly controlled by two antihypertensive drugs (systolic blood pressure \&gt; 150 mmHg or diastolic blood pressure \&gt; 100 mmHg);
10. Patients with poor glycemic control;
11. A history of ILD requiring steroid therapy, or current ILD or grade ≥2 radiation pneumonitis, or a suspicion of such disease;
12. Complicated with pulmonary diseases leading to clinically severe respiratory function impairment;
13. Patients with active central nervous system metastasis;
14. Had a severe infection within 4 weeks before randomization;
15. Patients with massive or symptomatic effusions or poorly controlled effusions;
16. Imaging examination showed that the tumor had invaded or enveloped the large blood vessels in the abdomen, chest, neck, and pharynx;
17. Serious unhealed wound, ulcer, or fracture within 4 weeks before signing the informed consent;
18. Subjects with clinically significant bleeding or obvious bleeding tendency within 4 weeks before signing the informed consent;
19. Patients with a history of inflammatory bowel disease, extensive bowel resection, immune enteritis, intestinal obstruction or chronic diarrhea;
20. Patients with a history of allergy to recombinant humanized antibodies or to any of the excipients of BL-B01D1;
21. Had autologous or allogeneic stem cell transplantation history;
22. Human immunodeficiency virus antibody positive, active hepatitis B virus infection or hepatitis C virus infection;
23. A history of severe neurological or psychiatric illness;
24. Received other unmarketed investigational drugs or treatments within 4 weeks before randomization;
25. Subjects scheduled for vaccination or who received live vaccine within 28 days before study randomization;
26. Other circumstances in which the investigator considered it inappropriate to participate in the trial because of complications or other circumstances.

Primary outcomes:
measure: Progression-free survival (PFS)
timeFrame: Up to approximately 36 months
Secondary outcomes:
measure: Overall survival (OS)
timeFrame: Up to approximately 36 months
measure: Objective Response Rate (ORR)
timeFrame: Up to approximately 36 months
measure: Disease Control Rate (DCR)
timeFrame: Up to approximately 36 months
measure: Duration of Response (DOR)
timeFrame: Up to approximately 36 months
measure: Treatment Emergent Adverse Event (TEAE)
timeFrame: Up to approximately 36 months
measure: Anti-drug antibody (ADA)
timeFrame: Up to approximately 36 months
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Shanghai East Hospital
state: Shanghai
Study officials:
References: