A Phase I Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetics Characteristics and Preliminary Efficacy of BL-M14D1 in Patients With Locally Advanced or Metastatic Small Cell Lung Cancer, Neuroendocrine Tumors and Other Solid Tumors
Overview
- Phase
- Phase 1
- Intervention
- BL-M14D1
- Conditions
- Small Cell Lung Cancer
- Sponsor
- Sichuan Baili Pharmaceutical Co., Ltd.
- Enrollment
- 22
- 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, dose-escalation and expansion-enrollment nonrandomized phase I clinical study to evaluate the safety, tolerability, pharmacokinetic characteristics and preliminary efficacy of BL-M14D1 in locally advanced or metastatic solid tumors.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Voluntarily sign the informed consent and follow the requirements of the protocol;
- •No gender limit;
- •Age: ≥18 years old and ≤75 years old (stage Ia); ≥18 years old (stage Ib);
- •Expected survival time ≥3 months;
- •Histologically and/or cytologically confirmed locally advanced or metastatic solid tumors that are incurable or currently have no standard treatment;
- •Consent to provide archival tumor tissue samples or fresh tissue samples from primary or metastatic lesions within 2 years;
- •Must have at least one measurable lesion according to RECIST v1.1 definition;
- •ECOG 0 or 1;
- •Toxicity of previous antineoplastic therapy has returned to ≤ grade 1 defined by NCI-CTCAE v5.0;
- •No severe cardiac dysfunction, left ventricular ejection fraction ≥50%;
Exclusion Criteria
- •Anti-tumor therapy such as chemotherapy or biological therapy has 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;
- •Prior receipt of an ADC drug with a TOPI inhibitor as a toxin;
- •History of severe heart disease or cerebrovascular disease;
- •QT prolongation, complete left bundle branch block, III degree atrioventricular block, frequent and uncontrollable arrhythmia;
- •Active autoimmune and inflammatory diseases;
- •Other malignant tumors diagnosed within 5 years before the first dose;
- •Hypertension poorly controlled by two antihypertensive drugs (systolic blood pressure \> 150 mmHg or diastolic blood pressure \> 100 mmHg);
- •A history of ILD requiring steroid therapy, or current ILD or grade ≥2 radiation pneumonitis according to the RTOG/EORTC definition, or suspicion of such a condition during screening;
- •Complicated pulmonary diseases leading to clinically severe respiratory function impairment;
- •Patients with massive or symptomatic effusions or poorly controlled effusions;
Arms & Interventions
BL-M14D1
Participants receive BL-M14D1 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-M14D1
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 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-M14D1.
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 .
Secondary Outcomes
- Tmax(Up to approximately 24 months)
- AUC0-t(Up to approximately 24 months)
- ADA (anti-drug antibody)(Up to approximately 24 months)
- Treatment-Emergent Adverse Event (TEAE)(Up to approximately 24 months)
- Cmax(Up to approximately 24 months)
- Ctrough(Up to approximately 24 months)
- T1/2(Up to approximately 24 months)
- CL (Clearance)(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)