A Phase I Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetic Characteristics and Preliminary Efficacy of BL-M24D1 for Injection in Patients With Locally Advanced or Metastatic Gastrointestinal Tumors and Other Solid Tumors
Trial Snapshot
- Phase
- Phase 1
- Status
- Not yet recruiting
- Enrollment
- 33
- Locations
- 1
- Primary Endpoint
- Phase Ia: Maximum tolerated dose (MTD)
Study Overview
Brief Summary
This study is an open, multicenter, non-randomized phase I clinical trial to evaluate the safety, tolerability, pharmacokinetic characteristics and preliminary efficacy of BL-M24D1 for Injection in patients with locally advanced or metastatic gastrointestinal tumors and other solid tumors.
Detailed Description
The study is divided into two phases: a dose escalation phase (Phase Ia) and a cohort expansion phase (Phase Ib).
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Voluntarily sign the informed consent form and comply with the protocol requirements;
- •No gender restrictions;
- •Age: ≥18 years and ≤75 years (Phase Ia); ≥18 years (Phase Ib);
- •Expected survival time ≥3 months;
- •Locally advanced or metastatic digestive tract tumors and other solid tumors;
- •Agree to provide archived tumor tissue specimens or fresh tissue samples from primary or metastatic lesions within the past 3 years;
- •Must have at least one measurable lesion meeting the RECIST v1.1 criteria;
- •ECOG performance status score of 0 or 1;
- •Toxicities from prior antitumor treatments have recovered to ≤ Grade 1 as defined by NCI-CTCAE v5.0;
- •No severe cardiac dysfunction, left ventricular ejection fraction ≥50%;
- •Organ function levels must meet the requirements;
- •Coagulation function: International Normalized Ratio (INR) ≤1.5, and activated partial thromboplastin time (APTT) ≤1.5 × ULN;
- •Urine protein ≤2+ or ≤1000mg/24h;
- •For premenopausal women with childbearing potential, a pregnancy test must be conducted within 7 days before starting treatment, serum pregnancy must be negative, and they must not be breastfeeding; all enrolled patients (regardless of gender) should adopt adequate barrier contraception throughout the treatment cycle and for 6 months after treatment ends.
Exclusion Criteria
- •Use of chemotherapy, biological therapy, or immunotherapy within 4 weeks prior to the first dose or within 5 half-lives;
- •History of severe heart disease;
- •QT interval prolongation, complete left bundle branch block, or third-degree atrioventricular block;
- •Active autoimmune or inflammatory diseases;
- •Diagnosis of other malignancies within 5 years prior to the first dose;
- •Hypertension poorly controlled by two antihypertensive medications;
- •Patients with poorly controlled blood glucose;
- •Unstable thrombotic events requiring therapeutic intervention within 6 months prior to the first dose;
- •Lung diseases graded ≥3 according to CTCAE v5.0;
- •Symptoms of active central nervous system metastases;
- •History of allergy to recombinant humanized antibodies or human-mouse chimeric antibodies, or allergy to any excipient component of BL-M24D1;
- •Previous organ transplantation or allogeneic hematopoietic stem cell transplantation (Allo-HSCT);
- •Cumulative dose of anthracyclines >360 mg/m² in previous (neo)adjuvant anthracycline therapy;
- •Human immunodeficiency virus antibody positivity, active tuberculosis, active hepatitis B virus infection, or active hepatitis C virus infection;
- •History of interstitial lung disease (ILD) requiring steroid treatment, or current ILD;
- •Active infection requiring systemic treatment within 4 weeks prior to the first investigational drug dose;
- •Pleural, abdominal, pelvic, or pericardial effusion requiring drainage and/or accompanied by symptoms within 4 weeks prior to the first investigational drug dose;
- •Subjects with clinically significant bleeding or obvious bleeding tendency within 4 weeks prior to the first investigational drug dose;
- •Participation in another clinical trial within 4 weeks prior to the first dose;
- •Pregnant or lactating women;
- •Other conditions deemed by the investigator as unsuitable for participation in this clinical trial.
Arms & Interventions
BL-M24D1
Participants receive BL-M24D1 as intravenous infusion for the first cycle (2 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-M24D1 (Drug)
Outcomes
Primary Outcomes
Phase Ia: Maximum tolerated dose (MTD)
Time Frame: Up to 28 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 Ia: Dose limiting toxicity (DLT)
Time Frame: Up to 28 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-M24D1.
Secondary Outcomes
- 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)
- Tmax(Up to approximately 24 months)
- T1/2(Up to approximately 24 months)
- AUC0-t(Up to approximately 24 months)
- CL (Clearance)(Up to approximately 24 months)
- Ctrough(Up to approximately 24 months)
- Phase Ib: Objective Response Rate (ORR)(Up to approximately 24 months)
- Phase Ib: Disease Control Rate (DCR)(Up to approximately 24 months)
- Phase Ib: Duration of Response (DOR)(Up to approximately 24 months)