A Phase I Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetics Characteristics and Preliminary Efficacy of BL-M05D1 in Patients With Locally Advanced or Metastatic Solid Tumors
Overview
- Phase
- Phase 1
- Intervention
- BL-M05D1
- Conditions
- Locally Advanced or Metastatic Solid Tumors
- Sponsor
- Sichuan Baili Pharmaceutical Co., Ltd.
- Enrollment
- 30
- Locations
- 1
- Primary Endpoint
- Phase Ia: Dose limiting toxicity (DLT)
- Status
- Recruiting
- Last Updated
- 10 months ago
Overview
Brief Summary
This study is an open-label, multicenter, dose-escalation, and extended-enrollment nonrandomized phase I study to evaluate the safety, tolerability, pharmacokinetic characteristics, and preliminary efficacy of BL-M05D1 in patients with locally advanced or metastatic 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;
- •Expected survival time ≥3 months;
- •locally advanced or metastatic solid tumors confirmed by histopathology and/or cytology with failure or intolerance to standard treatment or no standard treatment at present;
- •Consent to provide archival tumor tissue samples or fresh tissue samples from primary or metastatic lesions within 3 years;
- •At least one measurable lesion meeting the RECIST v1.1 definition was required;
- •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, immunotherapy 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 fluorouracil or palliative radiotherapy within 2 weeks before the first dose; Chinese patent medicine within 2 weeks before the first administration;
- •History of severe cardiovascular and cerebrovascular diseases;
- •Prolonged QT interval, 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;
- •had a history of ILD or a suspicion of such disease on imaging during screening; The patient was diagnosed with grade ≥1 radiation pneumonitis according to the RTOG/EORTC definition;
- •Pulmonary disease defined as grade ≥2 according to CTCAE v5.0; Pulmonary diseases lead to clinically severe respiratory function impairment;
- •patients with poor glycemic control;
- •patients with active central nervous system metastases;
Arms & Interventions
BL-M05D1
Participants receive BL-M05D1 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-M05D1
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-M05D1.
Secondary Outcomes
- Treatment-Emergent Adverse Event (TEAE)(Up to approximately 24 months)
- T1/2(Up to approximately 24 months)
- CL (Clearance)(Up to approximately 24 months)
- ADA (anti-drug antibody)(Up to approximately 24 months)
- AUC0-t(Up to approximately 24 months)
- Ctrough(Up to approximately 24 months)
- Cmax(Up to approximately 24 months)
- Tmax(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)
- Phase Ib: Disease Control Rate (DCR)(Up to approximately 24 months)