ACTengine IMA203 plus mRNA-4203 for cutaneous melanoma and synovial sarcoma
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)
Run by Immatics US, Inc. · NCT06946225 · Data updated 2026-11-12
This trial tests whether giving the ACTengine IMA203 T‑cell therapy together with the mRNA‑4203 vaccine is safe and helps people with HLA‑A*02:01 unresectable or metastatic cutaneous melanoma or synovial sarcoma who have had prior treatment.
Quick facts
| Phase | Phase 1 |
|---|---|
| Study type | Interventional |
| Ages | 18 Years and up |
| Sex | All |
| Enrollment | 15 (estimated) |
| Sponsor | Immatics US, Inc. Industry-sponsored |
| Drugs / interventions | cyclophosphamide, fludarabine |
| Locations | 4 sites (San Francisco, California and 3 other locations) |
| Status | Recruiting |
| Started | July 25, 2025 |
| Main results expected | August 2029 |
| Study ends | August 2029 |
| Registry record updated | January 8, 2026 |
| Trial ID | NCT06946225 on ClinicalTrials.gov |
Is this trial a fit for you?
✓Likely a good fit
Ideal candidates are HLA‑A*02:01 positive adults with unresectable or metastatic cutaneous melanoma who progressed after PD‑1 therapy, or synovial sarcoma patients who need additional systemic treatment, with ECOG 0–1 and measurable disease.
✕Probably not a fit
People who are HLA‑A*02:01 negative, have poor performance status, significant organ dysfunction, or active uncontrolled other malignancies are unlikely to qualify or benefit from this trial.
A plain-English reading of the study's rules. Only the study team can confirm whether you qualify.
What this trial studies
This is a multi-center, open-label Phase 1a/b trial combining the engineered T‑cell product IMA203 with escalating doses of the mRNA‑4203 vaccine in HLA‑A*02:01 positive adults with previously treated, unresectable or metastatic cutaneous melanoma or synovial sarcoma. The primary focus is on safety and tolerability across dose cohorts, with secondary endpoints measuring anti-tumor activity using RECIST 1.1. Eligible participants must have ECOG 0–1, adequate organ function, and measurable disease, with melanoma patients required to have progressed after prior PD‑1 therapy and synovial sarcoma patients needing further systemic therapy. Study procedures occur at specialist cancer centers and will establish recommended dosing for future studies if safety and signals of efficacy are observed.
Why it matters
Potential benefit: If successful, the combination could boost anti-tumor immune responses and potentially shrink tumors or delay disease progression compared with existing options.
How similar studies have gone: Related work with mRNA cancer vaccines and immune therapies has shown encouraging early signals in some cancers, but combining engineered T cells with an mRNA vaccine remains a relatively new approach with limited clinical proof so far.
Who can join: the full rules
Show full inclusion / exclusion 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
Where it's running
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University of California San Francisco
San Francisco, California, United States Recruiting -
Dana Farber Cancer Institute
Boston, Massachusetts, United States Recruiting -
Memorial Sloan Kettering Cancer Center
New York, New York, United States Recruiting -
MD Anderson Cancer Center
Houston, Texas, United States Recruiting
Study contacts
- Study coordinator: Immatics US, Inc.
- Email: ctgovinquiries@immatics.com
- Phone: +1 346 204-5400
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How to take part
- Review the eligibility criteria above with your treating physician.
- Check the official listing on ClinicalTrials.gov for the latest contact details and recruitment status.
- Contact the study coordinator or principal investigator to ask for pre-screening. Pre-screening is free and never obligates you to enroll.