A Study of BL-M08D1 in Patients With Locally Advanced or Metastatic Solid Tumors

Official title

A Phase I Study to Evaluate the Safety, Tolerability, Pharmacokinetic Characteristics and Preliminary Efficacy of BL-M08D1 for Injection in Patients With Locally Advanced or Metastatic Solid Tumors

Overview

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-M08D1 for injection in locally advanced or metastatic solid tumors.

Interventions

• Drug BL-M08D1
  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

• 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;
• Locally advanced or metastatic solid tumors confirmed by histopathology and/or cytology 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;
• 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%;
• No blood transfusion, no use of cell growth factors and/or platelet-raising drugs within 14 days before screening, and the organ function level must meet the requirements;
• Coagulation function: international normalized ratio (INR) ≤1.5, and activated partial thromboplastin time (APTT) ≤1.5ULN;
• Urinary protein ≤2+ or ≤1000mg/24h;
• For premenopausal women with childbearing potential, a pregnancy test must be performed within 7 days before starting treatment, serum pregnancy must be negative, and the patient must not be 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;
• Subjects were able and willing to comply with protocol-specified visits, treatment plans, laboratory tests, and other study-related procedures.

Exclusion criteria

• Chemotherapy, biological therapy 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 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;
• Hypertension poorly controlled by two antihypertensive drugs (systolic blood pressure \> 150 mmHg or diastolic blood pressure \> 100 mmHg);
• History of ILD requiring steroid therapy or current ILD or ≥ grade 2 radiation pneumonitis;
• Complicated with pulmonary diseases leading to clinically severe respiratory function impairment;
• Had 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-M08D1;
• Received previous organ transplantation or allogeneic hematopoietic stem cell transplantation (Allo-HSCT);
• Human immunodeficiency virus 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;
• Pleural, abdominal, pelvic or pericardial effusion requiring drainage and/or with symptoms within 4 weeks before the first dose of study drug;
• Received another trial drug 4 weeks or 5 half-lives before the first dose;
• Pregnant or lactating women;
• The investigator did not consider it appropriate to apply other criteria for participation in the trial.

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

• Fudan University Shanghai Cancer Center — Shanghai

Identifiers

NCT: NCT06718621 · BL-M08D1-101

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗