ACTengine® IMA203 Combined With mRNA-4203

NCT06946225 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: IMA203-102
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 4

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).

Conditions

Cutaneous Melanoma; Synovial Sarcoma

Keywords

immunotherapy; T-cell therapy; cutaneous melanoma; synovial sarcoma; RNA vaccine; Immatics; Moderna

Outcome Measures

Primary Outcomes (2)

• 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

  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

  one year post infusion of IMA203

Secondary Outcomes (5)

• Objective response rate (ORR)

  one year post infusion of IMA203

• Duration of response (DOR)

  one year post infusion of IMA203

• Disease control rate (DCR)

  one year post infusion of IMA203

• Progression-free survival (PFS)

  one year post infusion of IMA203

• Concentration of IMA203 transgene in peripheral blood

  one year post infusion of IMA203

Study Arms (1)

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.

Biological: IMA203; Biological: mRNA-4203

Interventions

IMA203 BIOLOGICAL

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.

Also known as: anzutresgene autoleucel, anzu-cel

IMA203 with mRNA-4203 in participants with metastatic cutaneous melanoma or synovial sarcoma

mRNA-4203 BIOLOGICAL

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.

Also known as: anzu-cel

IMA203 with mRNA-4203 in participants with metastatic cutaneous melanoma or synovial sarcoma

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Immatics US, Inc.: lead
• ModernaTX, Inc.: collaborator

Study Sites (4)

University of California San Francisco

San Francisco, California, 94143, United States

RECRUITING

Dana Farber Cancer Institute

Boston, Massachusetts, 02215, United States

RECRUITING

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

RECRUITING

MD Anderson Cancer Center

Houston, Texas, 77030, United States

RECRUITING

MeSH Terms

Conditions

Melanoma; Sarcoma, Synovial

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases; Neoplasms, Connective Tissue; Neoplasms, Connective and Soft Tissue; Sarcoma

Central Study Contacts

Immatics US, Inc.

CONTACT

+1 346 204-5400; ctgovinquiries@immatics.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 19, 2025
• First Posted: April 27, 2025
• Study Start: July 25, 2025
• Primary Completion (Estimated): August 1, 2029
• Study Completion (Estimated): August 1, 2029
• Last Updated: January 8, 2026

Record last verified: 2026-01

Locations

US (4)