A Study Comparing BL-B01D1 With Chemotherapy of Physician's Choice in Patients With Unresectable Locally Advanced or Metastatic Triple-Negative Breast Cancer

A Phase III Randomized Controlled Clinical Study Comparing BL-B01D1 With Chemotherapy of Physician's Choice in Patients With Unresectable Locally Advanced or Metastatic Triple-Negative Breast Cancer After Taxane Failure

This trial is a registered phase III, randomized, open-label, multicenter study designed to evaluate the efficacy and safety of BL-B01D1 in patients with unresectable locally advanced or metastatic Triple-Negative breast cancer after taxane failure.

Study Overview

• Status: Not yet recruiting
• Conditions: Triple-Negative Breast Cancer
• Intervention / Treatment: Drug: BL-B01D1; Drug: Eribulin; Drug: Vinorelbine; Drug: Gemcitabine; Drug: Capecitabine

• Study Type: Interventional
• Enrollment (Estimated): 436
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Sa Xiao, PHD; Phone Number: +8615013238943; Email: xiaosa@baili-pharm.com

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China
      • Fudan University Shanghai Cancer Center
      • Contact: Jiong Wu
      • Principal Investigator: Jian Zhang
      • Principal Investigator: Jiong Wu

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. No gender limit;
3. Age ≥18 years old and ≤75 years old;
4. Expected survival time ≥3 months;
5. Patients with unresectable, locally advanced or metastatic triple-negative breast cancer;
6. Consent to provide archival tumor tissue samples or fresh tissue samples of primary or metastatic lesions within 3 years;
7. The subjects had received 1-2 lines of chemotherapy regimens in the locally advanced or metastatic stage, and had been treated with taxanes previously;
8. Acceptability of chemotherapy with eribulin, capecitabine, gemcitabine, or vinorelbine, as assessed by the investigator;
9. Patients with baseline brain metastases should have received treatment for all brain metastases and be stable;
10. Must have at least one measurable lesion that meets the RECIST v1.1 definition;
11. ECOG score 0 or 1;
12. Toxicity of previous antineoplastic therapy has returned to ≤ grade 1 defined by NCI-CTCAE v5.0;
13. No severe cardiac dysfunction, left ventricular ejection fraction ≥50%;
14. No blood transfusion, no use of cell growth factors and/or platelet raising drugs within 14 days before the first use of the study drug, and the organ function level must meet the requirements;
15. Coagulation function: international normalized ratio ≤1.5, and activated partial thromboplastin time ≤1.5×ULN;
16. Urine protein ≤2+ or < 1000mg/24h;
17. For premenopausal women with childbearing potential, a pregnancy test must be performed within 7 days before the initiation of treatment, serum pregnancy must be negative, 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. Prior receipt of an ADC with a TOPI inhibitor as a toxin;
2. Prior receipt of an ADC or antibody drug targeting EGFR and/or HER3;
3. Chemotherapy, biological therapy, immunotherapy, etc. within 4 weeks or 5 half-lives before the first dose, small molecule targeted therapy within 5 days, palliative radiotherapy and anti-tumor therapy within 2 weeks;
4. Anthracycline equivalent cumulative dose of adriamycin > 360 mg/m2;
5. History of severe cardiovascular or cerebrovascular disease;
6. Unstable thrombotic events requiring therapeutic intervention within 6 months before screening;
7. QT prolongation, complete left bundle branch block, III degree atrioventricular block, frequent and uncontrollable arrhythmia;
8. Active malignancy diagnosed within 5 years before randomization;
9. Hypertension poorly controlled by two antihypertensive drugs;
10. Patients with poor blood glucose control before the first dose;
11. A history of interstitial lung disease requiring steroid therapy, or current radiation pneumonitis, or a suspicion of such disease;
12. Complicated with pulmonary diseases leading to clinically severe respiratory impairment;
13. Patients with carcinomatous meningitis (meningeal metastasis) or brain stem metastasis or spinal cord compression;
14. Have a history of allergy to recombinant humanized antibodies or any of the ingredients of BL-B01D1;
15. A history of autologous or allogeneic stem cell transplantation;
16. Human immunodeficiency virus antibody positive, active hepatitis B virus infection, or hepatitis C virus infection;
17. Severe infection within 4 weeks before randomization; Evidence of pulmonary infection or active pulmonary inflammation within 2 weeks before randomization;
18. Patients with massive or symptomatic effusions or poorly controlled effusions;
19. Imaging examination showed that the tumor had invaded or enveloped the large blood vessels in the abdomen, chest, neck, and pharynx;
20. Were receiving long-term systemic corticosteroids or equivalent active anti-inflammatory drugs or any form of immunosuppressive therapy before randomization;
21. Received other unmarketed investigational drug or treatment within 4 weeks before the first dose;
22. Patients with superior vena cava syndrome should not be rehydrated;
23. A history of severe neurological or mental illness;
24. Severe unhealed wound, ulcer, or fracture within 4 weeks before signing the informed consent;
25. Subjects with clinically significant bleeding or obvious bleeding tendency within 4 weeks before signing the informed consent;
26. History of intestinal obstruction, inflammatory bowel disease, or extensive bowel resection or presence of Crohn's disease, ulcerative colitis, or chronic diarrhea;
27. Patients scheduled for vaccination or receiving live vaccine within 28 days before the first dose;
28. 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.
Experimental: Eribulin or Vinorelbine or Gemcitabine or Capecitabine; Participants receive Eribulin or Vinorelbine or Gemcitabine or Capecitabine in 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: Eribulin; Administration by intravenous bolus for a cycle of 3 weeks.; Drug: Vinorelbine; Administration by intravenous infusion for a cycle of 3 weeks.; Drug: Gemcitabine; Administration by intravenous infusion for a cycle of 3 weeks.; Drug: Capecitabine; Oral administration for a cycle of 3 weeks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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

Secondary 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
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

Collaborators and Investigators

• Sponsor: Sichuan Baili Pharmaceutical Co., Ltd.
• Collaborators: Baili-Bio (Chengdu) Pharmaceutical Co., Ltd.
• Investigators: Principal Investigator: Jian Zhang, Fudan University; Principal Investigator: Jiong Wu, Fudan University

Study record dates

Study Major Dates

• Study Start (Estimated): May 1, 2024
• Primary Completion (Estimated): May 1, 2026
• Study Completion (Estimated): May 1, 2026

Study Registration Dates

• First Submitted: April 19, 2024
• First Submitted That Met QC Criteria: April 19, 2024
• First Posted (Actual): April 24, 2024

Study Record Updates

• Last Update Posted (Actual): May 14, 2024
• Last Update Submitted That Met QC Criteria: May 11, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Triple Negative Breast Neoplasms; Molecular Mechanisms of Pharmacological Action; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Capecitabine; Vinorelbine; Gemcitabine
• Other Study ID Numbers: BL-B01D1-307

Drug and device information, study documents

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