Cutaneous MelanomaPhase 1NCT06946225
ACTengine® IMA203 Combined With mRNA-4203
A Phase 1 study testing IMA203 and mRNA-4203 in people with Cutaneous Melanoma and Synovial Sarcoma, run by Immatics US, Inc. at 4 sites in United States.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Cutaneous Melanoma, Synovial Sarcoma
- What is being tested?
- IMA203 and mRNA-4203
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 15 participants
- Where
- 4 sitesUnited States
- Study dates
- 25 Jul 2025to Aug 2029
- Phase
- Phase 1
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Show all 10Show fewer
- 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
Who cannot join
- 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
Show all 15Show fewer
- 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
Trial locations and contacts
4 sites in 1 country. Contact the study team or a site near you to ask about taking part.
United States4 sites, 4 recruiting
- Recruiting
Dana Farber Cancer Institute
Boston, Massachusetts, 02215
Karam Khaddour, MD
Sydney Srnka, sydney_srnka@dfci.harvard.edu
- Recruiting
MD Anderson Cancer Center
Houston, Texas, 77030
Dejka Araujo, MD, daraujo@mdanderson.org
Rodabe Amaria, MD, RNAmaria@mdanderson.org
- Recruiting
Memorial Sloan Kettering Cancer Center
New York, New York, 10065
James Smithy, MD, smithyj@mskcc.org
- Recruiting
University of California San Francisco
San Francisco, California, 94143
Adil Daud, MD, hdfccc.cip@ucsf.edu
About this study
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)
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).
Read the 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).
- Conditions
- Cutaneous Melanoma, Synovial Sarcoma
- Being tested
- IMA203, mRNA-4203
- Keywords
- immunotherapy, T-cell therapy, cutaneous melanoma, synovial sarcoma, RNA vaccine, Immatics, Moderna
- Medical subject headings
- Melanoma, Sarcoma, Synovial
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
IMA203Biological
Also called anzutresgene autoleucel, anzu-cel
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.
mRNA-4203Biological
Also called anzu-cel
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.
| Study group | Role | What they receive |
|---|---|---|
| IMA203 with mRNA-4203 in participants with metastatic cutaneous melanoma or synovial sarcoma | Experimental | This is a non-comparative, open-label trial with different cohorts investigating IMA203 in combination with mRNA-4203. Receives: Biological: IMA203; Biological: mRNA-4203 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of participants with dose-limiting toxicities (DLTs)
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
Measured: 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
Used to evaluate safety and tolerability of treatment with IMA203 in combination with mRNA-4203
Measured: one year post infusion of IMA203
Secondary outcomes (5)
Objective response rate (ORR)
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
Measured: one year post infusion of IMA203
Duration of response (DOR)
CR and PR, locally assessed using RECIST v1.1
Measured: one year post infusion of IMA203
Disease control rate (DCR)
CR, PR and stable disease (SD) lasting 6 or more weeks following the infusion of IMA203, locally assessed using RECIST v1.1
Measured: one year post infusion of IMA203
Progression-free survival (PFS)
locally assessed using RECIST v1.1
Measured: one year post infusion of IMA203
Concentration of IMA203 transgene in peripheral blood
Evaluate the pharmacokinetics of T-cell receptor (TCR) engineered T cells in combination with mRNA-4203
Measured: one year post infusion of IMA203
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Apr 2025
- Study start25 Jul 2025
- Primary completionAug 2029 (estimated)
- Study completionAug 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Cutaneous MelanomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 15 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Immatics US, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- ModernaTX, Inc.
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06946225
- Sponsor's protocol ID
- IMA203-102
- Status last verified
- Jan 2026
- First submitted
- 19 Apr 2025
- Last updated
- 8 Jan 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 8 Jan 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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)
- ClinicalTrials.gov ID
- NCT06946225
- Acronym / sponsor ID
- IMA203-102
- Conditions
- Cutaneous Melanoma, Synovial Sarcoma
- Keywords
- immunotherapy, T-cell therapy, cutaneous melanoma, synovial sarcoma, RNA vaccine, Immatics, Moderna
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 15 participants (estimated)
- Lead sponsor
- Immatics US, Inc.Industry (pharma, biotech, devices)
- Collaborators
- ModernaTX, Inc.
- Study start
- 25 Jul 2025 (actual)
- Primary completion
- Aug 2029 (estimated)
- Study completion
- Aug 2029 (estimated)
- First posted
- 27 Apr 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| IMA203 with mRNA-4203 in participants with metastatic cutaneous melanoma or synovial sarcoma | Experimental | Biological: IMA203, Biological: mRNA-4203This is a non-comparative, open-label trial with different cohorts investigating IMA203 in combination with mRNA-4203. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- 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)
Key exclusion criteria (15 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| IMA203Also: anzutresgene autoleucel, anzu-celFollowing 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. | Biological | IMA203 with mRNA-4203 in participants with metastatic cutaneous melanoma or synovial sarcoma |
| mRNA-4203Also: anzu-celmRNA-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. | Biological | IMA203 with mRNA-4203 in participants with metastatic cutaneous melanoma or synovial sarcoma |
Primary outcome
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
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
5 secondary outcomes
Objective response rate (ORR)
Time frame: one year post infusion of IMA203
Duration of response (DOR)
Time frame: one year post infusion of IMA203
Disease control rate (DCR)
Time frame: one year post infusion of IMA203
Progression-free survival (PFS)
Time frame: one year post infusion of IMA203
Concentration of IMA203 transgene in peripheral blood
Time frame: one year post infusion of IMA203
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Jan 2026.
Related trials for Cutaneous Melanoma
Active, not recruitingPhase 3
Dabrafenib and Trametinib Followed by Ipilimumab and Nivolumab or Ipilimumab and Nivolumab Followed by Dabrafenib and Trametinib in Treating Patients With Stage III-IV BRAFV600 Melanoma
Clinical Stage III Cutaneous Melanoma AJCC v8, Clinical Stage IV Cutaneous Melanoma AJCC v8
Active, not recruitingPhase 2/3
A Phase II/III Trial of Nivolumab, Ipilimumab, and GM-CSF in Patients With Advanced Melanoma
Stage III Cutaneous Melanoma AJCC v7, Stage IV Cutaneous Melanoma AJCC v6 and v7
Active, not recruitingPhase 2
A Study to Compare the Administration of Pembrolizumab After Surgery Versus Administration Both Before and After Surgery for High-Risk Melanoma
Acral Lentiginous Melanoma, Clinical Stage III Cutaneous Melanoma AJCC v8
RecruitingPhase 2
BiCaZO: A Study Combining Two Immunotherapies (Cabozantinib and Nivolumab) to Treat Patients With Advanced Melanoma or Squamous Cell Head and Neck Cancer, an immunoMATCH Pilot Study
Clinical Stage III Cutaneous Melanoma AJCC v8, Clinical Stage III HPV-Mediated (p16-Positive) Oropharyngeal Carcinoma AJCC v8
Not yet recruitingObservational study
Clinical Genetics Branch Eligibility Screening Survey
Melanoma, Li-Fraumeni Syndrome
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing IMA203 and mRNA-4203 in people with Cutaneous Melanoma and Synovial Sarcoma, run by Immatics US, Inc. at 4 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 8 Jan 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Immatics US, Inc. (+1 346 204-5400, ctgovinquiries@immatics.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of participants with dose-limiting toxicities (DLTs) (time frame: one year post infusion of IMA203). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Jan 2026; AzTrials last refreshed its copy on 26 Oct 2026.