Clinical trial NCT06382116: A Study Comparing BL-B01D1 With Platinum Based Chemotherapy in Patients With Locally Advanced or Metastatic Non-small Cell Lung Cancer
Official title: A Phase III Randomized Controlled Clinical Study Comparing BL-B01D1 With Platinum Based Chemotherapy (First-line of Systemic Treatment) in Patients With Locally Advanced or Metastatic Non-small Cell Lung Cancer After EGFR-TKI Failure
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: 2024-04-24
Enrollment: 428
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 patients with locally advanced or metastatic non-squamous non-small cell lung cancer with EGFR-sensitive mutations after EGFR-TKI failure.


Eligibility criteria: Inclusion Criteria:

1. Voluntarily sign the informed consent and follow the requirements of the protocol;
2. Age ≥18 years old;
3. Expected survival time ≥3 months;
4. Histologically or cytologically confirmed locally advanced or metastatic non-squamous non-small cell lung cancer;
5. Documented classical EGFR mutations detected from tumor tissue or blood samples;
6. Had not received any systemic therapy other than EGFR-TKIs;
7. Radiographic disease progression documented during or after third-generation EGFR-TKI therapy for metastatic or locally advanced disease;
8. Consent to provide archival tumor tissue samples or fresh tissue samples of primary or metastatic lesions within 3 years;
9. Must have at least one measurable lesion according to RECIST v1.1 definition;
10. ECOG score 0 or 1;
11. Toxicity of previous antineoplastic therapy has returned to ≤ grade 1 defined by NCI-CTCAE v5.0;
12. No severe cardiac dysfunction, left ventricular ejection fraction ≥50%;
13. The level of organ function must meet the requirements on the premise that blood transfusion is not allowed within 14 days before the screening period and no cell growth factor drugs are allowed;
14. Coagulation function: international normalized ratio (INR) ≤1.5 and activated partial thromboplastin time (APTT) ≤1.5×ULN;
15. Urine protein ≤2+ or \< 1000mg/24h;
16. For premenopausal women with childbearing potential, a pregnancy test must be performed within 7 days before the start of treatment, serum or urine must be negative for pregnancy, and must be non-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. The patient has histologic or cytologic evidence of small cell or mixed small/non-small cell component or squamous non-small cell lung cancer;
2. Chemotherapy, biological therapy, immunotherapy, etc., have been used within 4 weeks or 5 half-lives before the first dose, small molecule targeted therapy has been used within 5 days, palliative radiotherapy or anti-tumor therapy has been used within 2 weeks;
3. Previous treatment with: a. an ADC with TOPI inhibitor as toxin; b. any systemic therapy in the context of metastatic/locally advanced disease;
4. The history of severe cardiovascular and cerebrovascular diseases in the past six months prior screening;
5. Thrombotic events requiring therapeutic intervention within 6 months before screening; Infusion-related thrombosis more than 4 weeks later was excluded;
6. Complete left bundle branch block, III degree atrioventricular block, frequent and uncontrolled severe arrhythmia;
7. Other malignancies diagnosed within 3 years before randomization;
8. Hypertension poorly controlled by two antihypertensive drugs;
9. History of interstitial lung disease (ILD) requiring steroid therapy, or current ILD or grade ≥2 radiation pneumonitis;
10. Patients with poor glycemic control;
11. Complicated pulmonary diseases leading to clinically severe respiratory function impairment;
12. Patients with active central nervous system (CNS) metastases;
13. Severe infection within 4 weeks before randomization; Evidence of pulmonary infection or active pulmonary inflammation within 2 weeks before randomization;
14. Patients with massive or symptomatic effusions or poorly controlled effusions;
15. Imaging examination showed that the tumor had invaded or wrapped the abdomen, chest, neck, and large blood vessels;
16. Severe unhealed wound, ulcer, or fracture within 4 weeks before signing the informed consent;
17. Subjects with clinically significant bleeding or obvious bleeding tendency within 4 weeks before signing the informed consent;
18. Patients with inflammatory bowel disease, extensive bowel resection history, immune enteritis history, intestinal obstruction or chronic diarrhea;
19. Have a history of allergy to recombinant humanized antibodies or any of the ingredients of BL-B01D1;
20. Human immunodeficiency virus antibody positive, active hepatitis B virus infection, or hepatitis C virus infection;
21. A history of severe neurological or psychiatric illness;
22. Received other unmarketed investigational drug or treatment within 4 weeks before randomization;
23. Subjects who were scheduled to receive live vaccine or received live vaccine within 28 days before study randomization;
24. Other circumstances that were assessed by the investigator as inappropriate for participation in the trial.

Primary outcomes:
measure: Progression-free survival (PFS)
timeFrame: Up to approximately 24 months
Secondary outcomes:
measure: Overall survival (OS)
timeFrame: Up to approximately 24 months
measure: Objective Response Rate (ORR)
timeFrame: Up to approximately 24 months
measure: Disease Control Rate (DCR)
timeFrame: Up to approximately 24 months
measure: Duration of Response (DOR)
timeFrame: Up to approximately 24 months
measure: Treatment Emergent Adverse Event (TEAE)
timeFrame: Up to approximately 24 months
measure: Anti-drug antibody (ADA)
timeFrame: Up to approximately 24 months
Other outcomes:
Locations:
city: Guangzhou
country: China
facility: Sun Yat-sen University Cancer Center
state: Guangdong
Study officials:
affiliation: Sun Yat-sen University
name: Li Zhang, PHD
role: PRINCIPAL_INVESTIGATOR
References: