ACTengine® IMA203 Combined With mRNA-4203

Официальное название

A First-in-human, Open-label Trial to Evaluate the Combination of ACTengine® IMA203 With mRNA-4203 in Previously Treated, Unresectable or Metastatic Cutaneous Melanoma or Synovial Sarcoma Patients (ACTengine® IMA203-102)

Обзор

This purpose of this clinical trial is to evaluate the safety, tolerability and anti-tumor activity of IMA203 in combination with different doses of mRNA-4203. The trial includes participants with previously treated unresectable or metastatic cutaneous melanoma (CM) or synovial sarcoma (SS).

Подробное описание

This clinical trial is a multi-center, open-label, non-comparative Phase 1 a/b trial to assess the safety, tolerability, and anti-tumor activity of the combination of IMA203 and mRNA-4203 in HLA-A\*02:01 positive patients with previously treated, unresectable or metastatic cutaneous melanoma (CM) and synovial sarcoma (SS).

Вмешательства

• Биопрепарат IMA203
  Following non-myeloablative chemotherapy for lymphodepletion (LD) with fludarabine (FLU) and cyclophosphamide (CY), participants will receive a single infusion of IMA203 on Day 1 and adjunctive therapy with low dose interleukin (IL)-2 for up to 10 days, starting approximately 24 h after IMA203 infusion.
• Биопрепарат mRNA-4203
  mRNA-4203 will be administered starting on Day 15 after IMA203 infusion at the earliest. mRNA-4203 will be given for 12 cycles (28 day cycle length); during Cycle 1 it will be given on Day 1 and Day 15 and in Cycles 2-12 it will be given on Day 1.

Первичные конечные точки

• Number of participants with dose-limiting toxicities (DLTs) [Срок оценки: one year post infusion of IMA203]
• Number of treatment emergent adverse events (AEs), AEs of special interest, serious AEs (SAEs), changes in laboratory parameters and vital signs, and frequency of dose interruptions, reductions and discontinuations [Срок оценки: one year post infusion of IMA203]

Вторичные конечные точки (5)

• Objective response rate (ORR) [Срок оценки: one year post infusion of IMA203]
• Duration of response (DOR) [Срок оценки: one year post infusion of IMA203]
• Disease control rate (DCR) [Срок оценки: one year post infusion of IMA203]
• Progression-free survival (PFS) [Срок оценки: one year post infusion of IMA203]
• Concentration of IMA203 transgene in peripheral blood [Срок оценки: one year post infusion of IMA203]

Критерии участия

Критерии включения

• Pathologically confirmed and documented cutaneous melanoma (CM) or synovial sarcoma (SS) with unresectable or metastatic disease
• HLA-A\*02:01 positive
• Adequate selected organ function per protocol
• Eastern Cooperative Oncology Group (ECOG) performance status 0-1
• Measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST 1.1)
• Life expectancy more than 5 months
• CM participants who must have disease progression (resistance, toxicity) on or after at least one PD-1 inhibitor
• SS participants must have received (or declined) at least one line of treatment (including SoC) and are still in need of further systemic therapy.
• Female participants of childbearing potential must use adequate contraception prior to trial entry until 12 months after the infusion of IMA203 and 15 days after the last mRNA 4203 dose administration

Other protocol defined inclusion criteria could apply

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
• History of cardiac conditions as per protocol
• Prior allogenic stem cell transplantation or solid organ transplantation
• Concurrent severe and/or uncontrolled medical disease that could compromise participation in the study
• History of hypersensitivity to cyclophosphamide, fludarabine, or IL-2
• History of hypersensitivity to mRNA-based medicines
• Positive for HIV infection or with active hepatitis B virus (HBV) or active hepatitis C virus (HCV) infection
• Any condition contraindicating leukapheresis
• Participants with lactate dehydrogenase (LDH) greater than threshold allowed per protocol
• Participants with active brain metastases prior to lymphodepletion
• Concurrent treatment in another clinical trial or a device trial that could interfere with the IMA203 treatment
• Participants with renal impairment AND reduced bone marrow reserve per protocol

Other protocol defined exclusion criteria could apply

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

США · 4 центра

• University of California San Francisco — San Francisco
• Dana Farber Cancer Institute — Boston
• Memorial Sloan Kettering Cancer Center — New York
• MD Anderson Cancer Center — Houston

Идентификаторы

NCT: NCT06946225 · IMA203-102

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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