A Study of Lutetium [177Lu] BL-ARC001 in Patients With Locally Advanced or Metastatic Gastrointestinal Tumors and Other Solid Tumors

Официальное название

A Phase I Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Preliminary Efficacy of Lutetium [177Lu] BL-ARC001 Injection in Patients With Locally Advanced or Metastatic Gastrointestinal Tumors and Other Solid Tumors

Обзор

This study is an open-label, multicenter, non-randomized Phase I clinical trial to evaluate the safety, tolerability, pharmacokinetic profile, 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 phases: a dose escalation phase (Phase Ia) and a 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 (12)

• 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]
• Distribution Characteristics [Срок оценки: Up to approximately 24 months]
• Radiation Characteristics [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]

Критерии участия

Критерии включения

• Voluntarily sign the informed consent form and comply with the protocol requirements;
• Gender: no restriction;
• Age: ≥18 years and ≤75 years (Phase Ia); ≥18 years (Phase Ib);
• Expected survival time ≥3 months;
• Locally advanced or metastatic solid tumors;
• Agree 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 meeting the RECIST v1.1 criteria;
• ECOG performance status score of 0 or 1;
• Toxicities from prior antitumor therapy have 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 ≤1.5, and activated partial thromboplastin time ≤1.5 × ULN;
• Urine 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 must not be breastfeeding; all enrolled patients (regardless of gender) should use adequate barrier contraception throughout the treatment cycle and for 6 months after treatment ends.

Критерии исключения

• Use of chemotherapy, biotherapy, or immunotherapy within 4 weeks or 5 half-lives (whichever is shorter) prior to the first dose;
• History of severe heart disease;
• QT interval prolongation, 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 steroid treatment, current ILD, or ≥ Grade 2 radiation pneumonitis;
• Symptoms of active central nervous system metastases;
• History of allergy to recombinant humanized or chimeric antibodies, or allergy to any excipient of Lutetium \[177Lu\] BL-ARC001;
• Previous organ transplantation or allogeneic hematopoietic stem cell transplantation;
• Cumulative dose of anthracyclines > 360 mg/m² in previous (neo)adjuvant anthracycline therapy;
• Positive human immunodeficiency virus antibody, active tuberculosis, active hepatitis B virus infection, or active hepatitis C virus infection;
• Active infection requiring systemic treatment;
• Participation in another clinical trial within 4 weeks prior to the first dose;
• Pregnant or lactating women;
• Any other condition 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

• Sichuan Cancer Hospital — Чэнду

Идентификаторы

NCT: NCT07232407 · 177Lu-BL-ARC001-102

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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