Clinical trial NCT06382142: A Study Comparing BL-B01D1 With Chemotherapy of Physician's Choice in Patients With Unresectable Locally Advanced or Metastatic Triple-Negative Breast Cancer
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Triple-Negative Breast 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: 406
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
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 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Progression-free survival (PFS)
timeFrame: Up to approximately 24 months
measure: Overall survival (OS)
timeFrame: Up to approximately 24 months
Secondary outcomes:
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: Shanghai
country: China
facility: Fudan University Shanghai Cancer Center
state: Shanghai
Study officials:
affiliation: Fudan University
name: Jiong Wu
role: PRINCIPAL_INVESTIGATOR
affiliation: Fudan University
name: Jian Zhang
role: PRINCIPAL_INVESTIGATOR
References: