A Phase I Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetics Characteristics and Preliminary Efficacy of BL-B16D1 in Patients With Unresectable Locally Advanced or Metastatic Breast Cancer and Other Solid Tumor
Overview
- Phase
- Phase 1
- Intervention
- BL-B16D1
- Conditions
- Breast Cancer
- Sponsor
- Sichuan Baili Pharmaceutical Co., Ltd.
- Enrollment
- 21
- Locations
- 1
- Primary Endpoint
- Phase Ia: Dose limiting toxicity (DLT)
- Status
- Recruiting
- Last Updated
- 7 months ago
Overview
Brief Summary
This study is an open, multicenter, increasing dose and dose extension nonrandomized phase I clinical study to evaluate the safety, tolerability, pharmacokinetics characteristics and preliminary efficacy of BL-B16D1 in patients with unresectable locally advanced or metastatic breast cancer and other solid tumor.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Sign the informed consent form voluntarily and follow the protocol requirements;
- •Gender is not limited;
- •Age: ≥18 years old and ≤75 years old (stage Ia); ≥18 years old (stage Ib);
- •Expected survival time ≥3 months;
- •Patients with histologically and/or cytologically confirmed unresectable locally advanced or metastatic breast cancer and other solid tumors who failed or could not receive standard treatment;
- •Consent to provide archival tumor tissue samples or fresh tissue samples from primary or metastatic lesions within 3 years;
- •Must have at least one extracranial measurable lesion that meets the RECIST v1.1 definition;
- •ECOG 0 or 1;
- •The toxicity of previous antineoplastic therapy has returned to ≤ grade 1 as defined by NCI-CTCAE v5.0;
- •No severe cardiac dysfunction, left ventricular ejection fraction ≥50%;
Exclusion Criteria
- •Chemotherapy, biological therapy and other anti-tumor therapies have been used within 4 weeks or 5 half-lives before the first dose; Mitomycin and nitrosoureas were administered within 6 weeks before the first dose; Oral drugs such as fluorouracil;
- •History of severe heart disease;
- •Prolonged QT interval, complete left bundle branch block, III degree atrioventricular block;
- •Active autoimmune and inflammatory diseases;
- •Patients with other malignant tumors or a history of other malignant tumors;
- •Unstable thrombotic events requiring therapeutic intervention within 6 months before screening; Infusion-related thrombosis was excluded;
- •Hypertension poorly controlled by two antihypertensive drugs (systolic blood pressure \> 150 mmHg or diastolic blood pressure \> 100 mmHg);
- •Patients with poor glycemic control;
- •Patients with grade ≥1 radiation pneumonitis according to the RTOG/EORTC definition; Previous history of ILD or current ILD, or suspicion of such disease during screening;
- •Complicated with pulmonary diseases leading to clinically severe respiratory function impairment;
Arms & Interventions
BL-B16D1
Participants receive BL-B16D1 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.
Intervention: BL-B16D1
Outcomes
Primary Outcomes
Phase Ia: Dose limiting toxicity (DLT)
Time Frame: Up to 21 days after the first dose
DLTs are assessed according to NCI-CTCAE v5.0 during the first cycle and defined as occurrence of any of the toxicities in DLT definition if judged by the investigator to be possibly, probably or definitely related to study drug administration.
Phase Ia: Maximum tolerated dose (MTD)
Time Frame: Up to 21 days after the first dose
MTD is defined as the highest dose level at which no more than 1 in 6 participants experienced a DLT during the first cycle .
Phase Ib: Recommended Phase II Dose (RP2D)
Time Frame: Up to approximately 24 months
The RP2D is defined as the dose level chosen by the sponsor (in consultation with the investigators) for phase II study, based on safety, tolerability, efficacy, PK, and PD data collected during the dose escalation study of BL-B16D1.
Secondary Outcomes
- Treatment-Emergent Adverse Event (TEAE)(Up to approximately 24 months)
- AUC0-t(Up to approximately 24 months)
- Cmax(Up to approximately 24 months)
- Tmax(Up to approximately 24 months)
- T1/2(Up to approximately 24 months)
- Phase Ib: Disease Control Rate (DCR)(Up to approximately 24 months)
- Phase Ib: Objective Response Rate (ORR)(Up to approximately 24 months)
- Phase Ib: Duration of Response (DOR)(Up to approximately 24 months)
- CL (Clearance)(Up to approximately 24 months)
- Ctrough(Up to approximately 24 months)
- ADA (anti-drug antibody)(Up to approximately 24 months)