RecruitingPhase 1NCT06946225

ACTengine® IMA203 Combined With mRNA-4203

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)

Sponsor

Immatics US, Inc.

Enrollment

15 participants

Start Date

Jul 25, 2025

Study Type

INTERVENTIONAL

Conditions

Cutaneous Melanoma Synovial Sarcoma

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).

Eligibility

Min Age: 18 Years

Inclusion Criteria9

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

Exclusion Criteria14

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

Interventions

BIOLOGICALIMA203

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.

BIOLOGICALmRNA-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.