A Phase I Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Preliminary Efficacy of BL-B16D1 in Patients With Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma and Other Solid Tumors
Overview
- Phase
- Phase 1
- Intervention
- BL-B16D1
- Conditions
- Head and Neck Squamous Cell Carcinomas
- 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, tolerance, pharmacokinetic characteristics and preliminary effectiveness of BL-B16D1 in recurrent or metastatic head and neck squamous cell carcinomas and other solid tumors.
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 (phase Ia); ≥18 years old (phase Ib);
- •Expected survival time ≥3 months;
- •Patients with pathologically and/or cytologically confirmed recurrent or metastatic head and neck squamous cell carcinoma and other solid tumors who failed or could not receive standard treatment;
- •Agreed to provide primary tumors or metastases 3 years archive of tumor tissue samples or fresh tissue samples;
- •Must have at least one accord with RECIST v1.1 define measurable lesions;
- •ECOG physical status 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
- •Antineoplastic therapy 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;
- •QT prolongation, complete left bundle branch block, III degree atrioventricular block;
- •Active autoimmune and inflammatory diseases;
- •Before the first delivery within 5 years diagnosed as other malignant tumor;
- •Hypertension poorly controlled by two antihypertensive drugs (systolic blood pressure \> 150 mmHg or diastolic blood pressure \> 100 mmHg);
- •Patients with poor glycemic control;
- •Present 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;
- •There is activity of the central nervous system symptoms;
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
- Cmax(Up to approximately 24 months)
- AUC0-t(Up to approximately 24 months)
- T1/2(Up to approximately 24 months)
- Phase Ib: Disease Control Rate (DCR)(Up to approximately 24 months)
- Treatment-Emergent Adverse Event (TEAE)(Up to approximately 24 months)
- Tmax(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)
- Phase Ib: Objective Response Rate (ORR)(Up to approximately 24 months)
- Phase Ib: Duration of Response (DOR)(Up to approximately 24 months)