A Study of BL-M09D1 in Patients With Locally Advanced or Metastatic Gastrointestinal Tumors and Other Solid Tumors

Official title

A Phase I Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetic Characteristics and Preliminary Efficacy of BL-M09D1 for Injection in Patients With Locally Advanced or Metastatic Gastrointestinal Tumors and Other Solid Tumors

Overview

This study is an open, multicenter, dose-escalation and expanded-enrollment, nonrandomized phase I clinical study to evaluate the safety, tolerability, pharmacokinetic characteristics and preliminary efficacy of BL-M09D1 for injection in patients with locally advanced or metastatic gastrointestinal tumors and other solid tumors.

Interventions

• Drug BL-M09D1
  Administration by intravenous infusion for a cycle of 3 weeks.

Primary outcome measures

• Phase Ia: Dose limiting toxicity (DLT) [Time frame: Up to 21 days after the first dose]
• Phase Ia: Maximum tolerated dose (MTD) [Time frame: Up to 21 days after the first dose]
• Phase Ib: Recommended Phase II Dose (RP2D) [Time frame: Up to approximately 24 months]

Secondary outcome measures (11)

• Treatment-Emergent Adverse Event (TEAE) [Time frame: Up to approximately 24 months]
• Cmax [Time frame: Up to approximately 24 months]
• Tmax [Time frame: Up to approximately 24 months]
• T1/2 [Time frame: Up to approximately 24 months]
• AUC0-t [Time frame: Up to approximately 24 months]
• CL (Clearance) [Time frame: Up to approximately 24 months]
• Ctrough [Time frame: Up to approximately 24 months]
• ADA (anti-drug antibody) [Time frame: Up to approximately 24 months]
• Phase Ib: Objective Response Rate (ORR) [Time frame: Up to approximately 24 months]
• Phase Ib: Disease Control Rate (DCR) [Time frame: Up to approximately 24 months]
• Phase Ib: Duration of Response (DOR) [Time frame: Up to approximately 24 months]

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 (phase Ia); ≥18 years old (phase Ib);
• Expected survival time ≥3 months;
• Pathologically and/or cytologically confirmed locally advanced or metastatic gastrointestinal tumors and other solid tumors that failed 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%;
• Organ function level must meet the requirements;
• Coagulation function: international normalized ratio (INR) ≤1.5, and activated partial thromboplastin time (APTT) ≤1.5ULN;
• Urine protein ≤2+ or ≤1000mg/24h;
• For premenopausal women with childbearing potential, a pregnancy test must be performed within 7 days before the initiation of treatment, serum pregnancy must be negative, and must be non-lactating; All enrolled patients (regardless of male or female) should use adequate barrier contraception during the whole treatment cycle and for 6 months after the end of treatment;
• Participants were able and willing to comply with protocol-specified visits, treatment plans, laboratory tests, and other study-related procedures.

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;
• History of severe heart disease;
• QT prolongation, complete left bundle branch block, III degree atrioventricular block;
• Active autoimmune and inflammatory diseases;
• Other malignant tumors diagnosed within 5 years before the first dose;
• Unstable thrombotic events requiring therapeutic intervention within 6 months before the first dose;
• Poorly controlled hypertension;
• Patients with poor glycemic control;
• History of ILD requiring steroid therapy, or current ILD or ≥ grade 2 radiation pneumonitis;
• Complicated pulmonary diseases leading to clinically severe respiratory function impairment;
• Symptoms of active central nervous system metastasis;
• Patients with a history of allergy to recombinant humanized antibody or human-mouse chimeric antibody or to any of the ingredients of BL-M09D1;
• Prior organ transplantation or allogeneic hematopoietic stem cell transplantation (Allo-HSCT);
• Anthracycline cumulative dose > 360 mg/m2 in previous (new) adjuvant therapy;
• HIV antibody positive, active tuberculosis, active hepatitis B virus infection, or active hepatitis C virus infection;
• Active infection requiring systemic therapy within 4 weeks before the first dose of study drug; Signs of pulmonary infection or active pulmonary inflammation within 2 weeks before the first dose;
• Pleural, abdominal, pelvic or pericardial effusion requiring drainage and/or with symptoms within 4 weeks before the first dose of study drug;
• Use of another clinical trial within 4 weeks or 5 half-lives before the first dose;
• Pregnant or lactating women;
• Other conditions for participation in the trial were not considered appropriate by the investigator.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

• Sun Yat-sen University Cancer Center — Guangzhou

Identifiers

NCT: NCT06954077 · BL-M09D1-101

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗