A Study of BL-M05D1 in Patients With Locally Advanced or Metastatic Solid Tumors

Official title

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

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.

Interventions

• Drug BL-M05D1
  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;
• 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%;
• 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 (male or female) were advised to use adequate barrier contraception throughout the treatment cycle and for 6 months after the end of treatment.

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;
• Patients with massive or symptomatic effusions, or poorly controlled effusions;
• Imaging examination showed that the tumor had invaded or wrapped around the chest, neck, pharynx and other large blood vessels;
• had a history of pulmonary embolism or a thrombotic event requiring therapeutic intervention within 6 months before screening; Infusion-related thrombosis was excluded;
• had a history of allergy to recombinant humanized antibody or human-mouse chimeric antibody or any of BL-M05D1 ingredients;
• prior organ transplantation or allogeneic hematopoietic stem cell transplantation (Allo-HSCT);
• The cumulative dose of anthracyclines > 360 mg/m2 in previous (new) adjuvant therapy;
• human immunodeficiency virus antibody positive, active tuberculosis, active hepatitis B virus infection or active hepatitis C virus infection;
• active infection requiring systemic therapy;
• had participated in another clinical trial within 4 weeks 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

• Beijing Cancer Hospital — Beijing

Identifiers

NCT: NCT06349811 · BL-M05D1-101

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗