A Study of BL-B01D1 Plus an Anti-PD-1 Antibody Versus Nab-paclitaxel Plus an Anti-PD-1 Antibody in Patients With Previously Untreated, Locally Advanced, Inoperable or Metastatic Triple-Negative Breast Cancer Whose Tumors Express PD-L1 (PANKU-Breast04)

Official title

A Phase III Randomized Controlled Clinical Study of BL-B01D1 Plus an Anti-PD-1 Antibody Versus Nab-paclitaxel Plus an Anti-PD-1 Antibody in Patients With Previously Untreated, Locally Advanced, Inoperable or Metastatic Triple-Negative Breast Cancer Whose Tumors Express PD-L1 (PANKU-Breast04)

Overview

This trial is a registrational Phase III, randomized, open-label, multicenter study designed to compare the efficacy and safety of BL-B01D1 in combination with a PD-1 monoclonal antibody versus nab-paclitaxel in combination with a PD-1 monoclonal antibody in patients with PD-L1-positive, previously untreated, inoperable locally advanced or recurrent metastatic triple-negative breast cancer.

Interventions

• Drug BL-B01D1
  Administration by intravenous infusion for a cycle of 3 weeks.
• Drug PD-1 monoclonal antibody
  Administration by intravenous infusion for a cycle of 3 weeks.
• Drug Nab-paclitaxel
  Administration by intravenous infusion for a cycle of 3 weeks.

Primary outcome measures

• BICR-assessed Progression-free Survival (PFS) [Time frame: Up to approximately 24 months]

Secondary outcome measures (12)

• Overall Survival (OS) [Time frame: Up to approximately 24 months]
• Investigator-assessed Progression-free Survival (PFS) [Time frame: Up to approximately 24 months]
• Objective Response Rate (ORR) [Time frame: Up to approximately 24 months]
• Disease Control Rate (DCR) [Time frame: Up to approximately 24 months]
• Duration of Response (DOR) [Time frame: Up to approximately 24 months]
• Time to Response (TTR) [Time frame: Up to approximately 24 months]
• Treatment Emergent Adverse Event (TEAE) [Time frame: Up to approximately 24 months]
• Cmax [Time frame: Up to approximately 24 months]
• Tmax [Time frame: Up to approximately 24 months]
• T1/2 [Time frame: Up to approximately 24 months]
• AUC0-t [Time frame: Up to approximately 24 months]
• CL (Clearance) [Time frame: Up to approximately 24 months]

Eligibility criteria

Inclusion criteria

• Voluntarily sign the informed consent form and agree to comply with the protocol requirements;
• Female patients aged 18 to 75 years;
• Expected survival time ≥ 3 months;
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1;
• Pathologically confirmed recurrent or metastatic triple-negative breast cancer;
• Confirmed PD-L1 expression positivity by central laboratory testing;
• No prior systemic anti-tumor therapy in the advanced/recurrent or metastatic setting;
• Agree to provide archived tumor tissue specimens (surgical specimens) or fresh tissue samples from primary or metastatic lesions obtained within 3 years;
• Must have at least one measurable lesion as defined by RECIST v1.1;
• Toxicities from prior anti-tumor therapy must have recovered to ≤ Grade 1 as defined by NCI-CTCAE v6.0;
• No severe cardiac dysfunction, with left ventricular ejection fraction (LVEF) ≥ 50%;
• Organ function levels must meet the protocol-specified requirements;
• Urine protein ≤ 1+ or < 1000 mg/24 h;
• For premenopausal women of childbearing potential, a pregnancy test (serum) must be performed within 7 days before starting treatment, and pregnancy must be ruled out; patients must not be lactating. All enrolled patients (regardless of sex) must use adequate barrier contraception throughout the entire treatment period and for 7 months after the end of treatment.

Exclusion criteria

• Received surgery, radical radiotherapy, or immunotherapy within 4 weeks before the first dose;
• Prior exposure to ADC drugs with topoisomerase I inhibitor payload;
• Prior treatment with other T-cell receptor-targeting agents (excluding PD-1/PD-L1);
• Use of immunomodulators within 14 days before the first study drug dose;
• History of severe cardiac or cerebrovascular disease;
• Receiving chronic systemic corticosteroids at >10 mg/day prednisone before the first dose;
• Active autoimmune or inflammatory disease;
• Any thrombotic event within 6 months before randomization;
• Prolonged QTc, complete left bundle branch block, or similar;
• Active malignancy diagnosed within 3 years before randomization;
• Hypertension uncontrolled by two antihypertensives;
• Poorly controlled diabetes/hyperglycemia;
• History of steroid-treated ILD/interstitial pneumonitis;
• Concurrent lung disease causing clinically significant respiratory impairment;
• Active CNS metastases;
• Severe infection within 4 weeks before randomization;
• Massive or symptomatic serosal effusion;
• Severe non-healing wound, ulcer, or fracture within 4 weeks before consent;
• Clinically significant bleeding or bleeding tendency within 4 weeks before consent;
• Inflammatory bowel disease, extensive bowel resection, immune enteritis, bowel obstruction, or chronic diarrhea;
• Allergy or contraindication to the study drug;
• History of autologous/allogeneic stem cell transplantation;
• HIV antibody positive, active HBV, or active HCV;
• History of severe neurological or psychiatric illness;
• Received or planning to receive live vaccine within 28 days before randomization;
• Other conditions rendering the patient unsuitable per investigator's judgment.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

• Fudan University Shanghai Cancer Center — Shanghai

Identifiers

NCT: NCT07729956 · BL-B01D1-325

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗