A Study of Lutetium [177Lu]-BL-ARC001 in Patients With Locally Advanced or Metastatic Lung Cancer, Breast Cancer, Head and Neck Squamous Cell Carcinoma and Other Solid Tumors

Официальное название

A Phase I Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetic Characteristics and Preliminary Efficacy of Lutetium [177Lu]-BL-ARC001 Injection in Patients With Locally Advanced or Metastatic Lung Cancer, Breast Cancer, Head and Neck Squamous Cell Carcinoma and Other Solid Tumors

Обзор

This study is an open, multicenter, dose-escalation and cohort-expansion non-randomized phase I clinical trial to evaluate the safety, tolerability, pharmacokinetic characteristics and preliminary efficacy of Lutetium \[177Lu\] BL-ARC001 in patients with locally advanced or metastatic solid tumors.

Подробное описание

The study is divided into two stages: the dose-escalation phase (Phase Ia) and the cohort-expansion phase (Phase Ib).

Вмешательства

• Препарат Lutetium [177Lu] BL-ARC001
  Administration by intravenous infusion for a cycle of 6 weeks.

Первичные конечные точки

• Phase Ia: Dose limiting toxicity (DLT) [Срок оценки: Up to 42 days after the first dose]
• Phase Ia: Maximum tolerated dose (MTD) [Срок оценки: Up to 42 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

• Voluntarily sign the informed consent form and comply with the protocol requirements;
• No gender restrictions;
• Age: ≥18 years and ≤75 years (Phase Ia); ≥18 years (Phase Ib);
• Expected survival time ≥3 months;
• Histologically or cytologically confirmed locally advanced or metastatic solid tumors that have failed standard treatment;
• Agreement to provide archived tumor tissue specimens or fresh tissue samples from primary or metastatic lesions within the past 3 years;
• Must have at least one measurable lesion as defined by RECIST v1.1;
• ECOG performance status score of 0 or 1;
• Toxicity from prior antitumor therapy has recovered to ≤ Grade 1 as defined by NCI-CTCAE v5.0;
• No severe cardiac dysfunction, left ventricular ejection fraction ≥50%;
• Organ function levels must meet the requirements;
• Coagulation function: International Normalized Ratio (INR) ≤1.5, and activated partial thromboplastin time (APTT) ≤1.5 × ULN;
• Urine protein ≤2+ or ≤1000mg/24h;
• For premenopausal women with childbearing potential, a serum pregnancy test must be performed within 7 days before starting treatment, and the result must be negative. Patients must not be breastfeeding; all enrolled patients (regardless of gender) should adopt adequate barrier contraception throughout the treatment cycle and for 6 months after treatment ends.

Критерии исключения

• Use of chemotherapy, biological therapy, or immunotherapy within 4 weeks or 5 half-lives prior to the first dose;
• History of severe heart disease;
• Prolonged QT interval, complete left bundle branch block, or third-degree atrioventricular block;
• Active autoimmune or inflammatory diseases;
• Diagnosis of other malignancies within 5 years prior to the first dose;
• Hypertension poorly controlled by two antihypertensive medications;
• History of interstitial lung disease (ILD) requiring hormonal therapy, current ILD, or ≥ Grade 2 radiation pneumonitis;
• Symptoms of active central nervous system metastasis;
• History of allergy to recombinant humanized antibodies or human-mouse chimeric antibodies, or allergy to any excipient component of 177Lu-BL-ARC001;
• Previous organ transplantation or allogeneic hematopoietic stem cell transplantation (Allo-HSCT);
• Cumulative dose of anthracyclines >360 mg/m² during prior (neo)adjuvant anthracycline therapy;
• Positive human immunodeficiency virus (HIV) antibody, active tuberculosis, active hepatitis B virus infection, or active hepatitis C virus infection;
• Active infection requiring systemic treatment, such as severe pneumonia, bacteremia, sepsis, etc.;
• Participation in another clinical trial within 4 weeks prior to the first dose;
• Pregnant or lactating women;
• Other conditions deemed by the investigator as unsuitable for participation in this clinical 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

• West China Hospital of Sichuan University — Чэнду

Идентификаторы

NCT: NCT07274852 · 177Lu-BL-ARC001-101

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗