Triple-Negative Breast Cancer (TNBC)
Conditions
Brief summary
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
DRUGBL-B01D1
Administration by intravenous infusion for a cycle of 3 weeks.
DRUGPD-1 monoclonal antibody
Administration by intravenous infusion for a cycle of 3 weeks.
DRUGNab-paclitaxel
Administration by intravenous infusion for a cycle of 3 weeks.
Sponsors
Sichuan Baili Pharmaceutical Co., Ltd.
Baili-Bio (Chengdu) Pharmaceutical Co., Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
1. Voluntarily sign the informed consent form and agree to comply with the protocol requirements; 2. Female patients aged 18 to 75 years; 3. Expected survival time ≥ 3 months; 4. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1; 5. Pathologically confirmed recurrent or metastatic triple-negative breast cancer; 6. Confirmed PD-L1 expression positivity by central laboratory testing; 7. No prior systemic anti-tumor therapy in the advanced/recurrent or metastatic setting; 8. Agree to provide archived tumor tissue specimens (surgical specimens) or fresh tissue samples from primary or metastatic lesions obtained within 3 years; 9. Must have at least one measurable lesion as defined by RECIST v1.1; 10. Toxicities from prior anti-tumor therapy must have recovered to ≤ Grade 1 as defined by NCI-CTCAE v6.0; 11. No severe cardiac dysfunction, with left ventricular ejection fraction (LVEF) ≥ 50%; 12. Organ function levels must meet the protocol-specified requirements; 13. Urine protein ≤ 1+ or \< 1000 mg/24 h; 14. 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
1. Received surgery, radical radiotherapy, or immunotherapy within 4 weeks before the first dose; 2. Prior exposure to ADC drugs with topoisomerase I inhibitor payload; 3. Prior treatment with other T-cell receptor-targeting agents (excluding PD-1/PD-L1); 4. Use of immunomodulators within 14 days before the first study drug dose; 5. History of severe cardiac or cerebrovascular disease; 6. Receiving chronic systemic corticosteroids at \>10 mg/day prednisone before the first dose; 7. Active autoimmune or inflammatory disease; 8. Any thrombotic event within 6 months before randomization; 9. Prolonged QTc, complete left bundle branch block, or similar; 10. Active malignancy diagnosed within 3 years before randomization; 11. Hypertension uncontrolled by two antihypertensives; 12. Poorly controlled diabetes/hyperglycemia; 13. History of steroid-treated ILD/interstitial pneumonitis; 14. Concurrent lung disease causing clinically significant respiratory impairment; 15. Active CNS metastases; 16. Severe infection within 4 weeks before randomization; 17. Massive or symptomatic serosal effusion; 18. Severe non-healing wound, ulcer, or fracture within 4 weeks before consent; 19. Clinically significant bleeding or bleeding tendency within 4 weeks before consent; 20. Inflammatory bowel disease, extensive bowel resection, immune enteritis, bowel obstruction, or chronic diarrhea; 21. Allergy or contraindication to the study drug; 22. History of autologous/allogeneic stem cell transplantation; 23. HIV antibody positive, active HBV, or active HCV; 24. History of severe neurological or psychiatric illness; 25. Received or planning to receive live vaccine within 28 days before randomization; 26. Other conditions rendering the patient unsuitable per investigator's judgment.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| BICR-assessed Progression-free Survival (PFS) | Up to approximately 24 months | Progression-free survival (PFS) as assessed by BICR is defined as the time between the date subjects were randomized and the first observation of disease progression (based on BICR's image-based assessment) or death. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Neutralizing Antibody(NAb) | Up to approximately 24 months | Frequency of anti-BL-B01D1 neutralizing antibodies will be investigated. |
| Overall Survival (OS) | Up to approximately 24 months | Overall survival (OS) is defined as the time between the day the subject is randomized and the subject's death. |
| Investigator-assessed Progression-free Survival (PFS) | Up to approximately 24 months | Investigator-assessed progression-free survival (PFS) per RECIST v1.1 is defined as the time from treatment initiation until the first documented disease progression according to RECIST v1.1 criteria, or death from any cause, whichever occurs first, as determined by the local treating investigator. |
| Objective Response Rate (ORR) | Up to approximately 24 months | 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). |
| Disease Control Rate (DCR) | Up to approximately 24 months | 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. |
| Duration of Response (DOR) | Up to approximately 24 months | 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. |
| Time to Response (TTR) | Up to approximately 24 months | Time to Response (TTR) is defined as the time from randomization to the first documented response (CR or PR) according to RECIST v1.1 criteria. |
| Treatment Emergent Adverse Event (TEAE) | Up to approximately 24 months | 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. |
| Cmax | Up to approximately 24 months | Maximum serum concentration (Cmax) of BL-B01D1 will be investigated. |
| Tmax | Up to approximately 24 months | Time to maximum serum concentration (Tmax) of BL-B01D1 will be investigated. |
| T1/2 | Up to approximately 24 months | Half-life (T1/2) of BL-B01D1 will be investigated. |
| AUC0-t | Up to approximately 24 months | AUC0-t is defined as area under the serum concentration-time curve from time 0 to the time of the last measurable concentration. |
| CL (Clearance) | Up to approximately 24 months | CL in the serum of BL-B01D1 per unit of time will be investigated. |
| Anti-drug Antibody (ADA) | Up to approximately 24 months | Frequency of anti-BL-B01D1 antibody (ADA) will be investigated. |
| Ctrough | Up to approximately 24 months | Ctrough is defined as the lowest serum concentration of BL-B01D1 prior to the next dose will be administered. |
Countries
China
Contacts
CONTACTSa Xiao, PHD
Outcome results
None listed