A Study Comparing BL-B01D1 With Topotecan in Patients With Recurrent Small Cell Lung Cancer(PANKU-Lung03)

A Phase III Randomized Controlled Clinical Study Comparing BL-B01D1 With Topotecan in Patients With Recurrent Small Cell Lung Cancer After Failure of Anti-PD-1/PD-L1 Monoclonal Antibodies and Platinum-based Chemotherapy

This trial is a registered phase III, randomized, open-label, multicenter study to evaluate the efficacy and safety of BL-B01D1 in patients with recurrent small cell lung cancer after failure of anti-PD-1/PD-L1 Monoclonal Antibodies and platinum-based chemotherapy.

Study Overview

• Status: Active, not recruiting
• Conditions: Small Cell Lung Cancer
• Intervention / Treatment: Drug: BL-B01D1; Drug: Topotecan

• Study Type: Interventional
• Enrollment (Actual): 722
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China
      • Sun Yat-sen University Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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. Patients with recurrent small-cell lung cancer after failure of anti-PD-1/PD-L1 monoclonal antibodies and platinum-based chemotherapy;
5. Consent to provide archival tumor tissue samples or fresh tissue samples of primary or metastatic lesions within 3 years;
6. Must have at least one measurable lesion according to RECIST v1.1 definition;
7. ECOG 0 or 1;
8. Toxicity of previous antineoplastic therapy has returned to ≤ grade 1 defined by NCI-CTCAE v5.0;
9. No severe cardiac dysfunction, left ventricular ejection fraction ≥50%;
10. The organ function level 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;
11. A serum pregnancy test must be performed within 7 days before the start of treatment for premenopausal fertile women, and the result must be negative and must not be lactating; All enrolled patients should take adequate barrier contraception during the entire treatment cycle and for 6 months after the end of treatment.

Exclusion Criteria:

1. The patient has histological or cytologic evidence of non-small cell lung cancer or mixed components of small cell lung cancer/non-small cell lung cancer;
2. Prior to randomization, chemotherapy, targeted therapy, or biological therapy were used within 4 weeks or 5 half-lives, small molecule targeted therapy was used within 5 days, or palliative radiotherapy was used within 2 weeks;
3. Patients with recurrent small cell lung cancer who are eligible for curative local therapy;
4. Received chemotherapy with TOP I inhibitor;
5. Received anti-EGFR and/or HER3 antibody /ADC drugs;
6. History of severe heart disease or cerebrovascular disease;
7. Unstable thrombotic events requiring therapeutic intervention within 6 months before screening; Infusion-related thrombosis was excluded;
8. Complete left bundle branch block, III degree atrioventricular block, frequent and uncontrollable arrhythmia;
9. Diagnosis of active malignancy within 3 years before randomization;
10. Hypertension poorly controlled by two antihypertensive drugs;
11. Patients with poor glycemic control;
12. A history of ILD requiring steroid therapy, or current ILD or grade ≥2 radiation pneumonitis;
13. Complicated pulmonary diseases leading to clinically severe respiratory function impairment;
14. Patients with active central nervous system metastases;
15. Severe infection within 4 weeks before randomization; There was evidence of pulmonary infection or active pulmonary inflammation requiring clinical intervention within 2 weeks before randomization;
16. Patients with massive or symptomatic effusions or poorly controlled effusions;
17. Imaging examination showed that the tumor had invaded or enveloped the large blood vessels in the abdomen, chest, neck, and pharynx;
18. Severe unhealed wound, ulcer, or fracture within 4 weeks before signing the informed consent;
19. Subjects with clinically significant bleeding or obvious bleeding tendency within 4 weeks before signing the informed consent;
20. Patients with inflammatory bowel disease, extensive bowel resection history, immune enteritis history, intestinal obstruction, chronic diarrhea or Gilbert's syndrome;
21. Patients with a history of allergy to recombinant humanized antibodies or to any of the excipients of BL-B01D1;
22. Human immunodeficiency virus antibody positive, active hepatitis B virus infection or hepatitis C virus infection;
23. A history of severe neurological or mental illness;
24. Subjects who were scheduled to receive live vaccine or received live vaccine within 28 days before study randomization;
25. Other circumstances that were assessed by the investigator as inappropriate for participation in the trial.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: BL-B01D1; Participants receive BL-B01D1 as intravenous infusion for the first cycle (3 weeks). Participants with clinical benefit could receive additional treatment for more cycles. The administration will be terminated because of disease progression or intolerable toxicity occurring or other reasons.	Drug: BL-B01D1; Administration by intravenous infusion for a cycle of 3 weeks.; Other Names: BMS-986507; iza-bren; izalontamab brengitecan
Experimental: Topotecan; Participants receive Topotecan as intravenous infusion for the first cycle (3 weeks). Participants with clinical benefit could receive additional treatment for more cycles. The administration will be terminated because of disease progression or intolerable toxicity occurring or other reasons.	Drug: Topotecan; Administration by intravenous infusion for a cycle of 3 weeks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival (OS)	Overall survival (OS) is defined as the time between the subject's randomization date and subject's death.	Up to approximately 24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate (ORR)	Objective response rate (ORR) is defined as the number of CR and PR in the treatment and control groups divided by the number of that group in the full analysis set (FAS).	Up to approximately 24 months
Disease Control Rate (DCR)	Disease Control Rate (DCR) : Percentage of all randomized subjects who rated the best overall response (BOR) as complete response (CR), partial response (PR), and disease stabilization (SD) according to RECIST 1.1 criteria.	Up to approximately 24 months
Duration of Response (DOR)	Duration of Response (DOR) : defined as the period from the date when tumor response is first recorded to the date when objective tumor progression is first recorded or the date of death.	Up to approximately 24 months
Treatment Emergent Adverse Event (TEAE)	TEAE is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally emerging, or any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a pre-existing condition during the treatment of BL-B01D1. The type, frequency and severity of TEAE will be evaluated during the treatment of BL-B01D1.	Up to approximately 24 months
Anti-drug antibody (ADA)	Frequency of anti-BL-B01D1 antibody (ADA) will be investigated.	Up to approximately 24 months
Progression-free survival (PFS)	Progression-free survival (PFS) as assessed by BIRC is defined as the time between the date subjects are randomized and the first observation of disease progression (based on BICR's image-based assessment) or death.	Up to approximately 24 months

Collaborators and Investigators

• Sponsor: Sichuan Baili Pharmaceutical Co., Ltd.
• Collaborators: Baili-Bio (Chengdu) Pharmaceutical Co., Ltd.
• Investigators: Principal Investigator: li Zhang, Sun Yat-sen University Cancer Center

Study record dates

Study Major Dates

• Study Start (Actual): August 7, 2024
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2026

Study Registration Dates

• First Submitted: July 8, 2024
• First Submitted That Met QC Criteria: July 8, 2024
• First Posted (Actual): July 15, 2024

Study Record Updates

• Last Update Posted (Actual): April 17, 2026
• Last Update Submitted That Met QC Criteria: April 15, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Respiratory Tract Diseases; Lung Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Small Cell Lung Carcinoma; Heterocyclic Compounds; Camptothecin; Alkaloids; Topotecan
• Other Study ID Numbers: BL-B01D1-304

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No