ACTengine® IMA203/IMA203CD8 as Monotherapy or in Combination With Nivolumab in Recurrent and/or Refractory Solid Tumors

Официальное название

Phase 1/2 Study Evaluating Genetically Modified Autologous T Cells Expressing a TCR Recognizing a Cancer/Germline Antigen as Monotherapy or in Combination With Nivolumab in Patients With Recurrent and/or Refractory Solid Tumors

Обзор

The study's purpose is to establish the safety and tolerability of IMA203/IMA203CD8 products with or without combination with nivolumab in patients with solid tumors that express preferentially expressed antigen in melanoma (PRAME).

Подробное описание

SCREENING: Patient eligibility will be determined by protocol inclusion/exclusion criteria including HLA (human leukocyte antigen) screening and a biopsy (or collection of archival tumor tissue) for biomarker screening. If the patient is eligible, white blood cells will be taken during leukapheresis for the manufacture of IMA203 or IMA203CD8 product.

MANUFACTURING: IMA203 or IMA203CD8 products will be made from the patients' white blood cells.

TREATMENT: Lymphodepletion with cyclophosphamide and fludarabine will occur in the days before the IMA203/IMA203CD8 product infusion to improve the duration of time that IMA203/IMA203CD8 product stays in the body. The patient will be admitted to the hospital during the T-cell infusion.

After the IMA203/IMA203CD8 product infusion, if applicable, a low dose of IL-2 will be given subcutaneously until day 10.

In Extension Cohort B (IMA203) nivolumab will be administered intravenously.

Patients will be monitored closely throughout the study. The follow-up phase ends 5 years post infusion.

Вмешательства

• Биопрепарат IMA203 Product
  The cell dose will be based on viable CD3+CD8+ HLA- Dextramer+ cells per body surface area (BSA) as defined by the Mosteller formula
• Биопрепарат IMA203 product- flat dose
  The cell dose will be based on viable CD3+CD8+ HLA- Dextramer+ cells
• Биопрепарат IMA203CD8 Product
  The cell dose will be based on viable CD3+CD8+ HLA- Dextramer+ cells per body surface area (BSA) as defined by the Mosteller formula
• Препарат Nivolumab
  Nivolumab will be given post IMA203/IMA203CD8 infusion, after hematologic recovery is achieved. Clinical supply provided by Bristol Myers Squibb.
• Устройство IMADetect®
  IMADetect® is developed as a companion diagnostic to aid in selecting patients with relapsed and/or refractory solid cancers who might be eligible for enrollment in Immatics clinical trials.

Первичные конечные точки

• Phase 1: Determine the MTD and/or recommended dose for extension for IMA203/IMA203CD8 [Срок оценки: 28 days]
• Phase 1 and Phase 2: Number and grade of treatment emergent adverse events and adverse events of special interest in subjects treated. [Срок оценки: 35 days]
• Phase 1 and Phase 2: Tumor Response [Срок оценки: 5 years]

Вторичные конечные точки (3)

• Phase 1 and 2: Persistence of TCR engineered T-cells [Срок оценки: up to 5 years post treatment]
• Phase 1 and 2: Tumor response [Срок оценки: up to 5 years]
• Phase 2: Patient reported quality of life [Срок оценки: up to 5 years]

Критерии участия

Критерии включения

• Patients must have recurrent/progressing and/or refractory solid tumors and must have received or not be eligible for all available indicated standard of care treatment.
• Eastern Cooperative Oncology Group (ECOG) performance status 0-1
• HLA-A\*02:01 positive
• For patients with ovarian/fallopian tube cancer only: Patients must have confirmed diagnosis of high-grade serous or endometrioid epithelial ovarian cancer (EOC), primary peritoneal cancer, or fallopian tube cancer.
• For patients with endometrial carcinoma only: Patients must have a histologically confirmed diagnosis of recurrent or persistent endometrial carcinoma.
• Measurable disease according to RECIST 1.1
• Adequate selected organ function per protocol
• Patient's tumor must express tumor antigen by "IMADetect® RT-qPCR. Retrospective testing will be required for patients that qualify.
• Life expectancy more than 5 months
• Female patient of childbearing potential must use adequate contraception prior to study entry until 12 months after the infusion of IMA203/IMA203CD8
• Male patient must agree to use effective contraception or be abstinent while on study and for 6 months after the infusion of IMA203/IMA203CD8
• The patient must have recovered from any side effects of prior therapy to Grade 1 or lower prior to lymphodepletion.

Критерии исключения

• History of other malignancies (except for adequately treated basal or squamous cell carcinoma or carcinoma in situ) within the last 3 years
• Pregnant or breastfeeding
• Serious autoimmune disease Note: At the discretion of the investigator, these patients may be included if their disease is well controlled without the use of immunosuppressive agents.
• History of cardiac conditions as per protocol
• Prior stem cell transplantation or solid organ transplantation
• Concurrent severe and/or uncontrolled medical disease that could compromise participation in the study
• History of or current immunodeficiency disease or prior treatment compromising immune function at the discretion of the treating physician
• Positive for HIV infection or with active hepatitis B virus (HBV) or active hepatitis C virus (HCV) infection.
• Patients with LDH greater than 2.0-fold ULN.
• Any condition contraindicating leukapheresis, lymphodepletion, low-dose IL-2, and/or IMA203/IMA203CD8 treatment
• Patients with active brain metastases
• Concurrent treatment in another clinical trial.
• For nivolumab treatment, patients must not have a history of severe immune-related toxicities, defined as any Grade 3 or 4 toxicities related to prior PD1/PD-L1 inhibitor therapy (e.g., atezolizumab, pembrolizumab or nivolumab etc.).

Other protocol defined inclusion/exclusion criteria could apply

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

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Нерандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

США · 13 центров

• Stanford Cancer Institute — Stanford
• University of Colorado, Anschutz Medical Campus — Aurora
• University of Miami Hospital and Clinics — Miami
• University of Chicago Medical Center — Chicago
• Massachusetts General Hospital — Boston
• Memorial Sloan Kettering Cancer Center — New York
• Ohio State University Wexner Medical Center Gynecologic Oncology at Mill Run — Columbus
• University of Pennsylvania, Perelamn Center for Advanced Medicine — Philadelphia
• … и ещё 5 центров

Германия · 8 центров

• Universitätsklinikum Heidelberg, Nationales Centrum für Tumorerkrankungen (NCT) — Heidelberg
• Klinikum rechts der Isar der Technischen Universität München — Munich
• Universitätsklinikum Würzburg — Würzburg
• Universitätsklinikum Bonn - Medizinische Klinik III — Bonn
• Universitätsmedizin der Johannes Gutenberg-Universität Mainz — Mainz
• Universitätsklinikum C.-G.-Carus Dresden — Dresden
• Charité Benjamin Franklin - Klinik für Hämatologie und Onkologie — Berlin
• Universitätsklinikum Hamburg-Eppendorf — Hamburg

Публикации

• Wermke M, Araujo DM, Chatterjee M, Tsimberidou AM, Holderried TAW, Jazaeri AA, Reshef R, Bokemeyer C, Alsdorf W, Wetzko K, Brossart P, Aslan K, Backert L, Bunk S, Fritsche J, Gulde S, Hengler S, Hilf N, Hossain MB, Hukelmann J, Kalra M, Krishna D, Kursunel MA, Maurer D, Mayer-Mokler A, Mendrzyk R, Mohamed A, Pozo K, Satelli A, Letizia M, Schuster H, Schoor O, Wagner C, Rammensee HG, Reinhardt C, S PMID 40205198

Идентификаторы

NCT: NCT03686124 · IMA203-101

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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