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

Официальное название

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

Обзор

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.

Вмешательства

• Препарат BL-M17D1
  Administration by intravenous infusion for a cycle of 3 weeks.

Первичные конечные точки

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

Вторичные конечные точки (11)

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

Критерии участия

Критерии включения

• 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.

Критерии исключения

• 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Китай · 2 центра

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

Идентификаторы

NCT: NCT06503783 · BL-M17D1-101

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗