A Study of BL-M17D1 in Patients With Locally Advanced or Metastatic HER2 Positive/Negative Breast Cancer and Other Solid Tumors

Official title

A Phase I Study to Evaluate the Safety, Tolerability, Pharmacokinetic Characteristics and Preliminary Efficacy of BL-M17D1 in Patients With Locally Advanced or Metastatic HER2 Positive/Negative Breast Cancer and Other 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-M17D1 in patients with locally advanced or metastatic HER2 positive/negative breast cancer and other solid tumors.

Interventions

• Drug BL-M17D1
  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 (stage Ia); ≥18 years old (stage Ib);
• Expected survival time ≥3 months;
• Patients with locally advanced or metastatic HER2-positive/negative breast cancer and other solid tumors;
• Agree to provide archival tumor tissue samples or fresh tissue samples of primary or metastatic lesions within 3 years;
• Must have at least one extracranial measurable lesion that meets the RECIST v1.1 definition;
• 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 is allowed within 14 days before the first use of the study drug, and no cell growth factor is allowed. The organ function level must meet the requirements;
• Coagulation function: international normalized ratio (INR) ≤1.5, and activated partial thromboplastin time (APTT) ≤1.5ULN;
• For premenopausal women of childbearing potential, a pregnancy test must be performed within 7 days before the initiation of 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 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;
• Prolonged QT interval, complete left bundle branch block, III degree atrioventricular block, frequent and uncontrollable arrhythmia;
• Active autoimmune and inflammatory diseases;
• Other malignancies diagnosed within 5 years before the first dose;
• Unstable thrombotic events requiring therapeutic intervention within 6 months before screening; Infusion-related thrombosis was excluded;
• Hypertension poorly controlled by two antihypertensive drugs (systolic blood pressure \> 150 mmHg or diastolic blood pressure \> 100 mmHg);
• A history of ILD requiring steroid therapy, or current ILD or radiation pneumonitis of grade ≥1 according to the RTOG/EORTC definition, or a suspicion of such disease;
• Patients with poor glycemic control;
• Complicated with pulmonary diseases leading to clinically severe respiratory function impairment;
• Patients with primary central nervous system tumors or CNS metastases after failure of local treatment;
• Patients with a history of allergy to recombinant humanized antibody or human-mouse chimeric antibody or to any of BL-M17D1's excipients;
• Prior organ transplantation or allogeneic hematopoietic stem cell transplantation;
• Prior anthracycline therapy with more than the protocol-specified cumulative dose of an anthracycline;
• Human immunodeficiency virus antibody positive, active tuberculosis, active hepatitis B virus infection or active hepatitis C virus infection;
• Active infection requiring systemic therapy with a serious infection within 4 weeks prior to informed consent; There were indications of pulmonary infection or active pulmonary inflammation within 2 weeks before informed consent;
• Patients with massive or symptomatic effusions, or poorly controlled effusions;
• Had participated in another clinical trial within 4 weeks before the first dose;
• Pregnant or lactating women;
• Patients with superior vena cava syndrome should not be rehydrated;
• A history of severe neurological or psychiatric illness;
• Severe unhealed wounds, ulcers, or fractures within 4 weeks before signing the informed consent;
• Subjects with clinically significant bleeding or obvious bleeding tendency within 4 weeks before signing the informed consent;
• History of intestinal obstruction, inflammatory bowel disease or extensive bowel resection or presence of Crohn's disease, ulcerative colitis or chronic diarrhea;
• Who are scheduled to receive live vaccine or who receive the vaccine within 28 days before the first dose;
• The investigators did not consider it appropriate to apply other conditions 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 · 2 centers

• Harbin Medical University Cancer Hospital — Harbin
• Fudan University Shanghai Cancer Center — Shanghai

Identifiers

NCT: NCT06503783 · BL-M17D1-101

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗