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RecruitingInterventionalPhase 3

A Prospective, Multicenter, Open-label, Randomized, Actively Controlled, Parallel-group Phase 3 Clinical Trial to Evaluate Efficacy, Safety, and Tolerability of IMA203 Versus Investigator's Choice of Treatment in Patients With Previously Treated, Unresectable or Metastatic Cutaneous Melanoma (ACTengine® IMA203-301)

NCT ID: NCT06743126Sponsor: Immatics US, Inc.Last updated: 2026-06-10

Summary

This clinical trial is a prospective, multicenter, open-label, randomized, actively controlled, parallel-group Phase 3 clinical trial to evaluate the efficacy, safety and tolerability of treatment with IMA203 administered at the recommended phase 2 dose versus investigator's choice of treatment in patients with previously treated, unresectable or metastatic cutaneous melanoma. For patients interested in additional information on how to participate, please follow this link: https://mytomorrows.com/trials/suprame/en-us/

Detailed description

SCREENING: Patient eligibility will be determined by protocol inclusion/exclusion criteria including HLA (human leukocyte antigen) screening. Leukapheresis for potential manufacturing of the IMA203 cellular product may be performed, if patients are HLA-A\*02:01 positive and meet the eligibility criteria for leukapheresis. MANUFACTURING: IMA203 products will be made from the patients' white blood cells. TREATMENT- Experimental arm: Lymphodepletion with cyclophosphamide and fludarabine will occur in the days before the IMA203 product infusion to improve the duration of time that IMA203 product stays in the body. The patient will be admitted to the hospital during the T-cell infusion. After the IMA203 product infusion, a low dose of IL-2 will be given subcutaneously for up to 10 days. TREATMENT- Control arm: Investigator's choice of treatment approved by the respective competent authority (nivolumab plus relatlimab \[Opdualag®\], lifileucel, nivolumab, pembrolizumab, ipilimumab, or chemotherapy \[e.g., dacarbazine, temozolomide, paclitaxel, alb-bound paclitaxel, or paclitaxel plus carboplatin\]) as determined by the site investigator in accordance with current respective prescribing information (PI) and/or summary of product characteristics (SmPC).

Arms & interventions

  • BiologicalIMA203

    one-time administration of IMA203, and adjunctive therapy with low dose interleukin (IL)-2 for up to 10 days, starting approximately 24 h after IMA203 infusion, optional bridging therapy

  • Biologicalnivolumab plus relatlimab

    in accordance with current respective prescribing information (PI) and/or summary of product characteristics (SmPC)

  • Biologicallifileucel

    in accordance with current respective prescribing information (PI) and/or summary of product characteristics (SmPC)

  • Biologicalnivolumab

    in accordance with current respective prescribing information (PI) and/or summary of product characteristics (SmPC)

  • Biologicalpembrolizumab

    in accordance with current respective prescribing information (PI) and/or summary of product characteristics (SmPC)

  • Biologicalipilimumab

    in accordance with current respective prescribing information (PI) and/or summary of product characteristics (SmPC)

  • DrugDacarbazine

    in accordance with current respective prescribing information (PI) and/or summary of product characteristics (SmPC)

  • Drugtemozolomide

    in accordance with current respective prescribing information (PI) and/or summary of product characteristics (SmPC)

  • Drugpaclitaxel

    in accordance with current respective prescribing information (PI) and/or summary of product characteristics (SmPC)

  • Drugpaclitaxel plus carboplatin

    in accordance with current respective prescribing information (PI) and/or summary of product characteristics (SmPC)

  • DrugAlbumin-Bound Paclitaxel

    in accordance with current respective prescribing information (PI) and/or summary of product characteristics (SmPC)

Outcome measures

Primary

  • Progression-free survival assessed by BICR

    progression-free survival (PFS), centrally assessed (by blinded independent central review) using RECIST 1.1

    Time frame: up to 5 years post first treatment of last patient

Secondary

  • Overall survival (OS)

    Time frame: up to 5 years post first treatment of last patient

  • Objective response rate (ORR)

    Time frame: up to 5 years post first treatment of last patient

  • Progression-free survival

    Time frame: up to 5 years post first treatment of last patient

  • Treatment-emergent adverse events (TEAEs)

    Time frame: until 85 days after cell therapy treatment or 30 days after last treatment

  • Adverse events of special interest (AESIs)

    Time frame: until 85 days after cell therapy treatment or 30 days after last treatment

  • Treatment-emergent serious adverse events (TESAEs)

    Time frame: until 85 days after cell therapy treatment or 30 days after last treatment

  • Frequency and duration of dose interruptions, reductions, and discontinuations

    Time frame: up to 5 years post first treatment of last patient

  • EORTC QLQ-C30

    Time frame: up to 5 years post first treatment of last patient

  • EQ-5D-5L

    Time frame: up to 5 years post first treatment of last patient

Eligibility criteria

Sex: AllAge: 18 Years and olderHealthy volunteers: No
Inclusion Criteria: * Pathologically confirmed and documented cutaneous melanoma- CM patients (including acral melanoma and melanoma of unknown primary) 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 * Disease progression (resistance, toxicity) on or after at least one PD-1 inhibitor, applied either as monotherapy or in combination with other therapies as treatment for unresectable or metastatic cutaneous melanoma * Patients with BRAF mutation should have been treated with one prior line of BRAF-directed therapy (with or without a MEK inhibitor) prior to initial eligibility assessment, unless deemed not clinically indicated at Investigator's discretion due to concurrent medical condition, prior toxicity, or if declined by the patient * Life expectancy more than 6 months * Measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST 1.1) * Female patient of childbearing potential must use adequate contraception from randomization until 12 months after the infusion of IMA203 or in line with the instructions provided for investigator's choice treatment (in the control arm) * Male patient must agree to use effective contraception or be abstinent while on study and for 6 months after the infusion of IMA203 or in line with the instructions provided for investigator's choice treatment (in the control arm) * The patient must have recovered from any side effects of prior therapy to Grade 1 or lower prior to randomization and prior to trial treatment start. Exclusion Criteria: * Primary mucosal or uveal melanoma * History of other malignancies (except for adequately treated basal or squamous cell carcinoma or carcinoma in situ) within the last 3 years * Serious autoimmune disease Note: At the discretion of the investigator, these patients may be included if their disease is well controlled without the use of immunosuppressive agents. * 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 or current immunodeficiency disease or prior treatment compromising immune function at the discretion of the treating physician * History of hypersensitivity to CY, FLU, or IL-2 or presence of any contraindications and other limitations for planned treatment with investigator's choice as laid down in the current versions of the respective PIs / SmPCs * Known hypersensitivity to any of the rescue medications * History of or current immunodeficiency disease or prior treatment compromising immune function at the discretion of the investigator * Positive for HIV infection or with active hepatitis B virus (HBV) or active hepatitis C virus (HCV) infection. * Any condition contraindicating leukapheresis * Pregnant or breastfeeding * Any other condition that would, in the investigator's or sponsor's judgment, contraindicate the patient's participation in the clinical trial because of safety concerns or compliance with clinical trial procedures (e.g., psychiatric disorders or substance dependence, neurological impairment) * Patient has received systemic corticosteroids within 2 weeks prior to leukapheresis, * Patient has received surgery or other anti-cancer therapies, any agent that is likely to suppress bone marrow function, or investigational medicinal products within 7 days prior to leukapheresis. * Patients with any active infection or ongoing reactivation of infection * Patients who underwent non-myeloablative lymphodepletion prior to cell therapy within the last 6 months * Prior treatment with IMA203 * Patients with ascites, pleural or pericardial effusion which requires repeated (2 within 4 weeks) or continuous paracentesis, thoracentesis or pericardiocentesis within last 2 months * Patients with LDH greater than 2.0-fold ULN * Concurrent treatment in another clinical trial or a device study that could interfere with the IMA203 treatment or planned investigator's choice treatment * Patients with active brain metastases or leptomeningeal metastases * Patient has received any investigational therapies, inactivated vaccines, chronic use of systemic corticosteroids or IV antibiotics within 1 week prior to randomization, or live vaccines within 4 weeks prior to randomization * Patient has received any anti-cancer therapy (prior anti-cancer treatment or bridging therapy) or radiotherapy within 1 week prior to start of trial treatment * Other protocol defined inclusion/exclusion criteria could apply

Study locations (40)

Mayo Clinic

Phoenix, Arizona, 85054

Recruiting
Seetharam Mahesh, MD · Contact

Honor Health Research Institute

Scottsdale, Arizona, 85258

Recruiting
Justin Moser, MD · Contact

City of Hope National Medical Center

Duarte, California, 91010

Recruiting
Yan Xing, MD · Contact

UC San Diego Moores Cancer Center

La Jolla, California, 92093

Recruiting
Gregory Daniels, MD · Contact

UCLA Hematology/Oncology

Los Angeles, California, 90024

Recruiting
Bartosz Chmielowski, MD, PhD · Contact

UCSF Helen Diller Family Comprehensive Cancer Center

San Francisco, California, 94143

Recruiting
Adil Daud, MD · Contact

Stanford Cancer Center

Stanford, California, 94305

Recruiting
Alison Betof Warner, MD, PhD · Contact

University of Colorado, Anschutz Medical Campus

Aurora, Colorado, 80045

Recruiting
Sapna Patel, MD · Contact

Yale Cancer Center

New Haven, Connecticut, 06510

Recruiting
Michael Hurwitz, MD, PhD · Contact

Mayo Clinic Florida

Jacksonville, Florida, 32224

Active Not Recruiting

University of Miami - Sylvester Comprehensive Cancer Cente

Miami, Florida, 33136

Recruiting
Leonel Hernandez-Aya, MD · Contact

Moffitt Cancer Center

Tampa, Florida, 33612

Recruiting
Lilit Karapetyan, MD, MS, FACP · Contact

University of Chicago Medical Center

Chicago, Illinois, 60637

Recruiting
Daniel Olson, MD · Contact

University of MD Greenebaum Comprehensive Cancer Center

Baltimore, Maryland, 21201

Recruiting
Petra Hausner, MD, PhD · Contact

Massachusetts General Hospital

Boston, Massachusetts, 02114

Recruiting
Alexandra (Lexi) Haugh, MD, MPH · Contact

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215

Recruiting
David McDermott, MD · Contact

University of Michigan

Ann Arbor, Michigan, 48109

Recruiting
Leslie Fecher, MD · Contact

Mayo Clinic

Rochester, Minnesota, 55905

Active Not Recruiting

University of Nebraska Medical Center

Omaha, Nebraska, 68198

Recruiting
Bhavina Sharma, MD · Contact

Atlantic Health System/Morristown Medical Center

Morristown, New Jersey, 07960

Recruiting
Eric Whitman, MD · Contact

Laura and Isaac Perlmutter Cancer Center at NYU Langone Health

New York, New York, 10016

Recruiting
Maya Dimitrova, MD · Contact

Memorial Sloan Kettering Cancer Center

New York, New York, 10065

Recruiting
James Smithy, MD · Contact

University of Rochester

Rochester, New York, 14642

Recruiting
Sahasrabudhe Deepak, MD · Contact

UNC Hospitals, The University of North Carolina at Chapel Hill

Chapel Hill, North Carolina, 27599

Recruiting
Stergios Moschos, MD · Contact

Cleveland Clinic, Taussig Cancer Institute

Cleveland, Ohio, 44195

Recruiting
James Isaac · Contact

Ohio State University

Columbus, Ohio, 43210

Recruiting
Richard Wu, MD, PhD · Contact

Providence Cancer Institute Franz Clinic

Portland, Oregon, 97213

Recruiting
Matthew Taylor, MD · Contact

Lehigh Valley Topper Cancer Institute

Allentown, Pennsylvania, 18103

Active Not Recruiting

University of Pennsylvania, Abramson Cancer Center

Philadelphia, Pennsylvania, 19104

Recruiting
Tara Mitchell, MD · Contact

Thomas Jeffersion University, Sidney Kimmel Cancer Center

Philadelphia, Pennsylvania, 19107

Recruiting
Rino Seedor, MD · Contact

Fox Chase Cancer Center

Philadelphia, Pennsylvania, 19111

Recruiting
Anthony J Olszanski, MD, RPh · Contact

UPMC Hillman Cancer Center

Pittsburgh, Pennsylvania, 15232

Recruiting
Diwakar Davar, M.D. · Contact
Jason J Luke, M.D. · Principal Investigator

Avera Cancer Institute

Sioux Falls, South Dakota, 57105

Recruiting
Benjamin Solomon, MD · Contact

SCRI Oncology Partners

Nashville, Tennessee, 37203

Recruiting
Meredith A McKean, MD, MPH · Contact

Baylor University

Dallas, Texas, 75246

Recruiting
Charles (Lance) Cowey, MD · Contact

University of Texas Southwestern Medical Center

Dallas, Texas, 75390

Recruiting
Sanjay Chandrasekaran, MD · Contact

The University of Texas MD Anderson Cancer Center

Houston, Texas, 77030

Recruiting
Rodabe N Amaria, MD · Contact

Huntsman Cancer Institute, University of Utah

Salt Lake City, Utah, 84112

Recruiting
Siwen Hu-Lieskovan, MD, PhD · Contact

Virginia Commonwealth University

Richmond, Virginia, 23219

Recruiting
Andrew Poklepovic, MD · Contact

Fred Hutchinson Cancer Center

Seattle, Washington, 98109

Recruiting
Sylvia Lee, MD · Contact