ACTengine® IMA203 Combined With mRNA-4203

January 6, 2026 updated by: Immatics US, Inc.

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)

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).

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Estimated)

15

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • United States
    • California
      • San Francisco, California, United States, 94143
        • Recruiting
        • University of California San Francisco
        • Contact:
    • Massachusetts
      • Boston, Massachusetts, United States, 02215
    • New York
      • New York, New York, United States, 10065
        • Recruiting
        • Memorial Sloan Kettering Cancer Center
        • Contact:
    • Texas

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: IMA203 with mRNA-4203 in participants with metastatic cutaneous melanoma or synovial sarcoma
This is a non-comparative, open-label trial with different cohorts investigating IMA203 in combination with mRNA-4203.
Biological: 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.
Other Names:
  • anzutresgene autoleucel
  • anzu-cel
Biological: 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.
Other Names:
  • anzu-cel

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of participants with dose-limiting toxicities (DLTs)
Time Frame: 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
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
Time Frame: one year post infusion of IMA203
Used to evaluate safety and tolerability of treatment with IMA203 in combination with mRNA-4203
one year post infusion of IMA203

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Objective response rate (ORR)
Time Frame: 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
one year post infusion of IMA203
Duration of response (DOR)
Time Frame: one year post infusion of IMA203
CR and PR, locally assessed using RECIST v1.1
one year post infusion of IMA203
Disease control rate (DCR)
Time Frame: 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
one year post infusion of IMA203
Progression-free survival (PFS)
Time Frame: one year post infusion of IMA203
locally assessed using RECIST v1.1
one year post infusion of IMA203
Concentration of IMA203 transgene in peripheral blood
Time Frame: one year post infusion of IMA203
Evaluate the pharmacokinetics of T-cell receptor (TCR) engineered T cells in combination with mRNA-4203
one year post infusion of IMA203

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Immatics US, Inc.

Collaborators

ModernaTX, Inc.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

July 25, 2025

Primary Completion (Estimated)

August 1, 2029

Study Completion (Estimated)

August 1, 2029

Study Registration Dates

First Submitted

April 19, 2025

First Submitted That Met QC Criteria

April 19, 2025

First Posted (Actual)

April 27, 2025

Study Record Updates

Last Update Posted (Actual)

January 8, 2026

Last Update Submitted That Met QC Criteria

January 6, 2026

Last Verified

January 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • IMA203-102

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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