ACTengine® IMA203 Combined With mRNA-4203

Phase 1

Not yet recruiting

• Conditions: Cutaneous Melanoma; Synovial Sarcoma
• Interventions: Biological: IMA203; Biological: mRNA-4203

• Registration Number: NCT06946225
• Lead Sponsor: Immatics US, Inc.

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).

Study Timeline

• Status Verified: 2025-04
• Study First Submitted: 2025-04-19
• Study First Submitted QC: 2025-04-19
• Study First Posted: 2025-04-27
• Study Start: 2025-05
• Last Update Submitted: 2025-05-02
• Last Update Posted: 2025-05-06
• Primary Completion: 2029-08
• Study Completion: 2029-08

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 15

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
IMA203 with mRNA-4203 in participants with metastatic cutaneous melanoma or synovial sarcoma	IMA203	This is a non-comparative, open-label trial with different cohorts investigating IMA203 in combination with mRNA-4203.
IMA203 with mRNA-4203 in participants with metastatic cutaneous melanoma or synovial sarcoma	mRNA-4203	This is a non-comparative, open-label trial with different cohorts investigating IMA203 in combination with mRNA-4203.

Primary Outcome Measures

Name	Time	Method
Number of participants with dose-limiting toxicities (DLTs)	one year post infusion of IMA203	Number of DLTs will be used to determine the maximum tolerated dose (MTD) and/or recommended dose for extension (RDE) after treatment with IMA203 product in combination with mRNA-4203
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	one year post infusion of IMA203	Used to evaluate safety and tolerability of treatment with IMA203 in combination with mRNA-4203

Secondary Outcome Measures

Name	Time	Method
Objective response rate (ORR)	one year post infusion of IMA203	complete response (CR) and partial response (PR) based on best overall response (BOR), locally assessed using Response Evaluation Criteria in Solid Tumors (RECIST) v1.1
Duration of response (DOR)	one year post infusion of IMA203	CR and PR, locally assessed using RECIST v1.1
Disease control rate (DCR)	one year post infusion of IMA203	CR, PR and stable disease (SD) lasting 6 or more weeks following the infusion of IMA203, locally assessed using RECIST v1.1
Progression-free survival (PFS)	one year post infusion of IMA203	locally assessed using RECIST v1.1
Concentration of IMA203 transgene in peripheral blood	one year post infusion of IMA203	Evaluate the pharmacokinetics of T-cell receptor (TCR) engineered T cells in combination with mRNA-4203