A Phase I Trial of A-CAR032 in Participants With mCRPC

Официальное название

First Time-in-Human (FTiH), Phase I Trial to Evaluate the Safety, Cellular Kinetics, and Efficacy of A-CAR032, in Adult Participants With Metastatic Castration-Resistant Prostate Cancer (mCRPC)

Обзор

This FTiH, single-arm, open-label, investigator-initiated Phase I trial will evaluate the safety, antitumour activity, CK/pharmacodynamics (PD), biomarkers, immunogenicity, and feasibility of A-CAR032 in adult participants with mCRPC, who have previously progressed after ARPI treatment of prostate cancer (whether before or in the metastatic castration-resistant setting) and, in the judgment of the investigator, are ineligible for standard treatment.

Подробное описание

The study consists of two parts: Part 1-Dose Escalation and Part 2-Dose Expansion. Participants in the study will proceed through screening, apheresis, bridging therapy (if appropriate), lymphodepletion, CAR-T cell infusion, and subsequent follow-up (including Stage 1, 2 and 3).

Вмешательства

• Биопрепарат dnTGFβRII-armoured STEAP2-targeted autologous CAR T-Cell Injection
  dnTGFβRII-armoured STEAP2-targeted autologous CAR T-Cell Injection.single infusion intravenously.

Первичные конечные точки

• Dose Escalation (Part 1)：Safety [Срок оценки: From ICF signature until 15 years post A-CAR032 infusion]
• Dose Escalation (Part 1)：Safety [Срок оценки: Throughout the 28 days post A-CAR032 infusion]
• Dose Escalation (Part 1)：Safety [Срок оценки: From ICF signature until 12 months post A-CAR032 infusion]
• Dose Expansion (Part 2)：Safety [Срок оценки: From ICF signature until 15 years post A-CAR032 infusion]
• Dose Expansion (Part 2)：Safety [Срок оценки: Throughout the 28 days post A-CAR032 infusion]
• Dose Expansion (Part 2)：Safety [Срок оценки: From ICF signature until 12 months post A-CAR032 infusion]

Вторичные конечные точки (6)

• Dose Escalation (Part 1) and Dose Expansion (Part 2)：Efficacy [Срок оценки: From ICF signature until 12 months post A-CAR032 infusion]
• Dose Escalation (Part 1) and Dose Expansion (Part 2)：Efficacy [Срок оценки: From ICF signature until 12 months post A-CAR032 infusion]
• Dose Escalation (Part 1) and Dose Expansion (Part 2)：Efficacy [Срок оценки: From ICF signature until 12 months post A-CAR032 infusion]
• Dose Escalation (Part 1) and Dose Expansion (Part 2)：Efficacy [Срок оценки: From ICF signature until 15 years post A-CAR032 infusion]
• Dose Escalation (Part 1) and Dose Expansion (Part 2)：Efficacy [Срок оценки: From A-CAR032 infusion until 12 months post A-CAR032 infusion]
• Dose Escalation (Part 1) and Dose Expansion (Part 2)：Pharmacokinetics [Срок оценки: From ICF signature until 15 years post A-CAR032 infusion]

Критерии участия

Критерии включения

• Participant must be 18 years or older at the time of signing the ICF. Type of Participant and Disease Characteristics
• Participants with:

• A histologically confirmed diagnosis of metastatic adenocarcinoma of the prostate without known neuroendocrine differentiation or small cell features.
• Castration-resistant prostate cancer as defined by disease progression despite castration by orchiectomy or ongoing luteinising hormone-releasing hormone analogue. Participants receiving medical castration therapy with gonadotropin-releasing hormone analogues should continue this treatment during the study.
• Measurable PSA≥1 ng/mL AND
• Evidence of progression within 6 months prior to screening
• Participant has previously received an ARPI (ie, abiraterone, enzalutamide, apalutamide, darolutamide, rezvilutamide) whether before or in the metastatic castration-resistant setting, and in the judgment of the investigator, be ineligible for standard treatment.
• Minimum life expectancy of > 12 weeks prior to apheresis in the opinion of the investigator.
• Adequate organ and marrow function
• Consent and provision of tumour material to assess STEAP2 expression and other correlative biomarkers retrospectively with pre- and post-treatment biopsies.
• Contraceptive use should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
• The participant voluntarily participates in the study, and the individual or their legal guardian signs the ICF.

Критерии исключения

• Known life-threatening allergies, hypersensitivity, or intolerance to the CAR-T product or its excipients, including dimethyl sulfoxide (DMSO).
• Contraindication to lymphodepleting agents, including fludarabine and/or cyclophosphamide.
• History of another primary malignancy except for:

• Malignancy treated with curative intent and with no known active disease within 3 years before the apheresis and of low potential risk for recurrence.
• Adequately treated non-melanoma skin cancer or lentigo malignancy without evidence of disease.
• Adequately treated carcinoma in situ without evidence of disease.
• Participants with known brain metastases.
• History of splenectomy or organ transplantation.
• Prior treatment with:

• Any CAR-T therapy. OR
• Any therapy that is targeting STEAP2.
• Active or prior documented autoimmune or inflammatory disorders
• Cardiac arrhythmias which are symptomatic or require treatment unless controlled by pacemaker (judged by investigator); symptomatic or uncontrolled atrial fibrillation despite treatment, or asymptomatic sustained ventricular tachycardia.
• Active infection, including:

• HBV infection is defined as hepatitis B surface antigen (HBsAg) positive, or hepatitis B core antibody (HBcAb) positive and HBV DNA detectable.
• HCV infection is defined as HCV antibody positive and HCV RNA positive.
• CMV infection is defined as CMV DNA detectable.
• Syphilis infection is defined as syphilis antigen and antibody positive.
• HIV infection is defined as HIV 1/2 antibody positive.
• Other persistent or active infections requiring systemic treatment (prophylactic use of anti-infective drugs is allowed).
• Patients with central nervous system (CNS) diseases:
• Obvious risk or tendency of bleeding or active bleeding (eg, clinically significant hemoptysis, tumour bleeding, history of von Willebrand disease or hemophilia etc.).
• Plans to father a child during the study period.
• Patients with alcohol or drug abuse.
• Participants may not receive full-dose long acting oral or parenteral anticoagulants or thrombolytic agents for therapeutic (as opposed to prophylactic) purpose from the time of informed consent to 28 days post infusion of A-CAR032. Use of short acting direct oral anticoagulants for therapeutic and prophylactic purposes are permitted.
• Received the following:

• Major surgery within 4 weeks prior to apheresis or existence of unhealed wound, or planned major surgery within 4 weeks of the study treatment administration
• Steroids (except inhaled steroids) or other immunomodulators (including interleukins, interferons, and thymosins) of systemic therapeutic dose, and systemic corticosteroids at doses exceeding 10 mg/day of prednisone or equivalent within 5 half-lives or 7 days (whichever is shorter) prior to apheresis.
• Receipt of the last dose of anticancer therapy (chemotherapy, immunotherapy, endocrine therapy targeted therapy, biologic therapy, tumour embolisation, or monoclonal antibodies, investigational product) within 5 half-lives or ≤ 21 days (whichever is shorter) prior to apheresis.
• Radiotherapy within 4 weeks of apheresis (However, if the radiation portal covered ≤ 5% of the bone marrow reserve, the participant is eligible irrespective of the end date of radiotherapy); or within 6 months or 5 half-lives (whichever is longer) if local radioactive particle implantation was performed.

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

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Последовательный дизайн

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Китай · 5 центров

• Beijing Cancer Hospital — Пекин
• Beijing GoBroad Hospital — Пекин
• Tongji Hospital, Tongji Medical College of HUST — Ухань
• The Affiliated Hospital of Xuzhou Medical University — Xuzhou
• The First Affiliated Hospital, Zhejiang University School of Medicine — Ханчжоу

Идентификаторы

NCT: NCT07344311 · 1332-046

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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