Clinical trial NCT06946225: ACTengine® IMA203 Combined With mRNA-4203
Official title: 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)
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE1
Conditions: Cutaneous Melanoma
Synovial Sarcoma
Keywords: immunotherapy
T-cell therapy
cutaneous melanoma
synovial sarcoma
RNA vaccine
Immatics
Moderna
Lead sponsor: Immatics US, Inc.
Sponsor class: INDUSTRY
Collaborators: name: ModernaTX, Inc.
First posted: 2025-04-27
Enrollment: 15
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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).

Detailed description: 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).

Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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

Primary outcomes:
measure: Number of participants with dose-limiting toxicities (DLTs)
timeFrame: one year post infusion of IMA203
measure: 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
timeFrame: one year post infusion of IMA203
Secondary outcomes:
measure: Objective response rate (ORR)
timeFrame: one year post infusion of IMA203
measure: Duration of response (DOR)
timeFrame: one year post infusion of IMA203
measure: Disease control rate (DCR)
timeFrame: one year post infusion of IMA203
measure: Progression-free survival (PFS)
timeFrame: one year post infusion of IMA203
measure: Concentration of IMA203 transgene in peripheral blood
timeFrame: one year post infusion of IMA203
Other outcomes:
Locations:
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