A Study of BL-B16D1 in Patients With Unresectable Locally Advanced or Metastatic Breast Cancer and Other Solid Tumors

Официальное название

A Phase I Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetics Characteristics and Preliminary Efficacy of BL-B16D1 in Patients With Unresectable Locally Advanced or Metastatic Breast Cancer and Other Solid Tumor

Обзор

This study is an open, multicenter, increasing dose and dose extension nonrandomized phase I clinical study to evaluate the safety, tolerability, pharmacokinetics characteristics and preliminary efficacy of BL-B16D1 in patients with unresectable locally advanced or metastatic breast cancer and other solid tumor.

Вмешательства

• Препарат BL-B16D1
  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 histologically and/or cytologically confirmed unresectable locally advanced or metastatic breast cancer and other solid tumors who failed or could not receive standard treatment;
• Consent to provide archival tumor tissue samples or fresh tissue samples from 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%;
• The organ function level must meet the requirements if the patient has not received blood transfusion or hematopoietic stimulation factor therapy within 14 days before the first dose;
• Coagulation function: international normalized ratio ≤1.5, and activated partial thromboplastin time ≤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) should use adequate contraception throughout the treatment cycle and for 6 months after completion 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;
• Active autoimmune and inflammatory diseases;
• Patients with other malignant tumors or a history of other malignant tumors;
• 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);
• Patients with poor glycemic control;
• Patients with grade ≥1 radiation pneumonitis according to the RTOG/EORTC definition; Previous history of ILD or current ILD, or suspicion of such disease during screening;
• Complicated with pulmonary diseases leading to clinically severe respiratory function impairment;
• Patients with primary central nervous system (CNS) tumors or CNS metastases that had failed local treatment;
• Patients with a history of allergy to recombinant humanized antibody or human-mouse chimeric antibody or to any of BL-B16D1's excipients;
• Received previous organ transplantation or allogeneic hematopoietic stem cell transplantation (Allo-HSCT);
• In previous (new) adjuvant anthracyclines, the cumulative dose of anthracyclines for doxorubicin > 550 mg/m2, epirubicin > 900 mg/m2 or the equivalent dose of other similar drugs;
• Human immunodeficiency virus antibody positive, active tuberculosis, active hepatitis B virus infection or active hepatitis C virus infection;
• Serious infection occurred within 4 weeks before the first dose; Signs of pulmonary infection or active pulmonary inflammation within 2 weeks before the first dose;
• Patients with massive or symptomatic effusions, or poorly controlled effusions;
• Had participated in another clinical trial within 4 weeks before the first dose (calculated from the time of the last dose);
• Had the following eye diseases: a. active infection or corneal ulcer; b. monocular vision; c. a history of corneal transplantation; d. Contact lens dependence; e. Uncontrolled glaucoma; f. Uncontrolled or progressive retinopathy, wet macular degeneration, etc.;
• Other circumstances that the investigator deemed inappropriate 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 · 1 центр

• Fudan University Shanghai Cancer Center — Шанхай

Идентификаторы

NCT: NCT06493864 · BL-B16D1-103

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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