A Study Comparing BL-B01D1 With Chemotherapy of Physician's Choice in Patients With Unresectable Locally Advanced, Recurrent, or Metastatic HR+HER2- Breast Cancer(PANKU-Breast01)

A Phase III Randomized Controlled Clinical Study Comparing BL-B01D1 With Chemotherapy of Physician's Choice in Patients With Unresectable Locally Advanced, Recurrent, or Metastatic HR+HER2- Breast Cancer After Failure of at Least One Prior Line of 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 unresectable locally advanced, recurrent, or metastatic HR+HER2- breast cancer after failure of at least one prior line of chemotherapy.

Study Overview

• Status: Active, not recruiting
• Conditions: HR+HER2- Breast Cancer
• Intervention / Treatment: Drug: BL-B01D1; Drug: Eribulin; Drug: Vinorelbine; Drug: Gemcitabine; Drug: Capecitabine

• Study Type: Interventional
• Enrollment (Actual): 383
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Beijing Municipality
    • Beijing, Beijing Municipality, China
      • Cancer Hospital Chinese Academy of Medical Sciences

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;
4. expected survival time ≥3 months;
5. Patients with unresectable locally advanced, recurrent metastatic HR+HER2- breast cancer;
6. The subjects had received 1-2 lines of chemotherapy regimens in the unresectable locally advanced recurrence or metastasis stage, and had been treated with endocrine, CDK4/6 inhibitors, and taxanes;
7. Documented radiographic disease progression;
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. No blood transfusion, no use of cell growth factors and/or platelet raising drugs within 14 days before screening, and the organ function level must meet the requirements;
14. Urine protein ≤2+ or < 1000mg/24h;
15. 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 it 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 drug with a topoisomerase I inhibitor as a toxin;
2. Prior receipt of an ADC or antibody drug targeting EGFR and/or HER3;
3. 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, modern Chinese medicine preparations approved by NMPA for anti-tumor therapy, etc., have been used within 2 weeks;
4. anthracycline equivalent cumulative dose of adriamycin > 360 mg/m2;
5. History of severe cardiovascular or cerebrovascular disease;
6. Unstable deep vein thrombosis, arterial thrombosis, and pulmonary embolism requiring medical 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. Other malignant tumors diagnosed within 3 years before the first dose;
9. Hypertension poorly controlled by two antihypertensive drugs; Patients with poor glycemic control;
10. A history of interstitial lung disease (ILD) requiring steroid therapy, current ILD or grade ≥2 radiation pneumonitis, or suspicion of such disease on imaging during screening;
11. Complicated pulmonary diseases leading to clinically severe respiratory function impairment;
12. Patients with active central nervous system metastases;
13. Patients with massive or symptomatic effusions or poorly controlled effusions;
14. Imaging examination showed that the tumor had invaded or wrapped around the large blood vessels in the abdomen, chest, neck, and pharynx;
15. Severe infection within 4 weeks before randomization; Evidence of pulmonary infection or active pulmonary inflammation within 2 weeks before randomization;
16. Was receiving > before randomization; Long-term systemic corticosteroid therapy with 10mg/ day prednisone or equivalent anti-inflammatory active drugs or any form of immunosuppressive therapy;
17. Severe 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 inflammatory bowel disease, extensive bowel resection history, immune enteritis history, intestinal obstruction or chronic diarrhea;
20. Have a history of allergy to recombinant humanized antibodies or to BL-B01D1 and any excipients; A history of autologous or allogeneic stem cell transplantation;
21. Human immunodeficiency virus antibody positive, active hepatitis B virus infection or hepatitis C virus infection;
22. A history of severe neurological or psychiatric illness;
23. Received other unmarketed investigational drug or treatment within 4 weeks before the first dose; A live vaccine dose within 28 days before the planned dose or the first dose;
24. Any complications or other circumstances deemed by the investigator to preclude 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: 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: Binghe Xu, Cancer Institute and Hospital, Chinese Academy of Medical Sciences

Study record dates

Study Major Dates

• Study Start (Actual): April 24, 2024
• Primary Completion (Estimated): May 1, 2026
• Study Completion (Estimated): May 1, 2026

Study Registration Dates

• First Submitted: March 27, 2024
• First Submitted That Met QC Criteria: March 27, 2024
• First Posted (Actual): April 3, 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; Skin Diseases; Breast Diseases; Breast Neoplasms; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Nucleic Acids, Nucleotides, and Nucleosides; Alkaloids; Indoles; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Nucleosides; Uracil; Pyrimidinones; Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Indolizidines; Indolizines; Deoxyribonucleosides; Fluorouracil; Capecitabine; Vinorelbine; Gemcitabine; eribulin
• Other Study ID Numbers: BL-B01D1-306

Drug and device information, study documents

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