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SUPRAME-ACTengine® IMA203 vs. Investigator's Choice of Treatment in Previously Treated, Unresectable or Metastatic Cutaneous Melanoma
NCT06743126 · Immatics US, Inc.
In plain English
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Official title
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)
About this study
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).
Eligibility criteria
Inclusion Criteria:
* Pathologically confirmed and documented cutaneous melanoma- CM patients (including acral melanoma) 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.
Exclusion Criteria:
* Primary mucosal or uveal melanoma and melanoma of unknown primary
* 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 design
Enrollment target: 360 participants
Allocation: randomized
Masking: none
Age groups: adult, older_adult
Timeline
Starts: 2025-01-14
Estimated completion: 2031-10
Last updated: 2026-04-13
Interventions
Biological: IMA203Biological: nivolumab plus relatlimabBiological: lifileucelBiological: nivolumabBiological: pembrolizumabBiological: ipilimumabDrug: DacarbazineDrug: temozolomideDrug: paclitaxelDrug: paclitaxel plus carboplatinDrug: Albumin-Bound Paclitaxel
Primary outcomes
- • Progression-free survival assessed by BICR (up to 5 years post first treatment of last patient)
Sponsor
Immatics US, Inc. · industry
Contacts & investigators
ContactImmatics US, Inc. · contact · ctgovinquiries@immatics.com · +1 346 204-5400
InvestigatorCedrik Britten, M.D. · study_director, Immatics US, Inc.
All locations (58)
Mayo ClinicRecruiting
Phoenix, Arizona, United States
Honor Health Research InstituteRecruiting
Scottsdale, Arizona, United States
City of Hope National Medical CenterRecruiting
Duarte, California, United States
UC San Diego Moores Cancer CenterRecruiting
La Jolla, California, United States
UCLA Hematology/OncologyRecruiting
Los Angeles, California, United States
UCSF Helen Diller Family Comprehensive Cancer CenterRecruiting
San Francisco, California, United States
Stanford Cancer CenterRecruiting
Stanford, California, United States
Yale Cancer CenterRecruiting
New Haven, Connecticut, United States
Mayo Clinic FloridaActive Not Recruiting
Jacksonville, Florida, United States
University of Miami - Sylvester Comprehensive Cancer CenteRecruiting
Miami, Florida, United States
Moffitt Cancer CenterRecruiting
Tampa, Florida, United States
University of Chicago Medical CenterRecruiting
Chicago, Illinois, United States
University of MD Greenebaum Comprehensive Cancer CenterRecruiting
Baltimore, Maryland, United States
Massachusetts General HospitalRecruiting
Boston, Massachusetts, United States
Beth Israel Deaconess Medical CenterRecruiting
Boston, Massachusetts, United States
University of MichiganActive Not Recruiting
Ann Arbor, Michigan, United States
Mayo ClinicActive Not Recruiting
Rochester, Minnesota, United States
University of Nebraska Medical CenterRecruiting
Omaha, Nebraska, United States
Atlantic Health System/Morristown Medical CenterRecruiting
Morristown, New Jersey, United States
Laura and Isaac Perlmutter Cancer Center at NYU Langone HealthRecruiting
New York, New York, United States
Memorial Sloan Kettering Cancer CenterRecruiting
New York, New York, United States
University of RochesterRecruiting
Rochester, New York, United States
UNC Hospitals, The University of North Carolina at Chapel HillRecruiting
Chapel Hill, North Carolina, United States
Cleveland Clinic, Taussig Cancer InstituteRecruiting
Cleveland, Ohio, United States
Ohio State UniversityRecruiting
Columbus, Ohio, United States
Providence Cancer Institute Franz ClinicRecruiting
Portland, Oregon, United States
University of Pennsylvania, Abramson Cancer CenterRecruiting
Philadelphia, Pennsylvania, United States
Thomas Jeffersion University, Sidney Kimmel Cancer CenterRecruiting
Philadelphia, Pennsylvania, United States
Fox Chase Cancer CenterRecruiting
Philadelphia, Pennsylvania, United States
UPMC Hillman Cancer CenterRecruiting
Pittsburgh, Pennsylvania, United States
Avera Cancer InstituteRecruiting
Sioux Falls, South Dakota, United States
SCRI Oncology PartnersRecruiting
Nashville, Tennessee, United States
Baylor UniversityRecruiting
Dallas, Texas, United States
University of Texas Southwestern Medical CenterRecruiting
Dallas, Texas, United States
The University of Texas MD Anderson Cancer CenterRecruiting
Houston, Texas, United States
Huntsman Cancer Institute, University of UtahRecruiting
Salt Lake City, Utah, United States
Virginia Commonwealth UniversityRecruiting
Richmond, Virginia, United States
Fred Hutchinson Cancer CenterRecruiting
Seattle, Washington, United States
BC Cancer - VancouverActive Not Recruiting
Vancouver, British Columbia, Canada
University Health Network, Princess Margaret Cancer CentreRecruiting
Toronto, Ontario, Canada
Universitatsklinikum KoelnRecruiting
Cologne, Northrhine-W Estphalia, Germany
Charite Universitaetsmedizin Berlin KöRRecruiting
Berlin, Germany
Universitaetsklinikum Bonn AöRNot Yet Recruiting
Bonn, Germany
Technische Universitaet DresdenRecruiting
Dresden, Germany
Universitaetsklinikum Erlangen AöRRecruiting
Erlangen, Germany
Universitaetsklinikum Essen AöRRecruiting
Essen, Germany
Goethe University FrankfurtRecruiting
Frankfurt am Main, Germany
University Medical Center Hamburg-EppendorfRecruiting
Hamburg, Germany
Universitaetsklinikum Heidelberg AöRRecruiting
Heidelberg, Germany
Universitaet LeipzigRecruiting
Leipzig, Germany
Universitaetsmedizin der Johannes Gutenberg-Universitaet Mainz KöRRecruiting
Mainz, Germany
Cambridge University Hospitals NHS Foundation Trust, Addenbrooke's HospitalNot Yet Recruiting
Cambridge, United Kingdom
Greater Glasgow and Clyde NHS, Beatson West of Scotland Cancer CenterNot Yet Recruiting
Glasgow, United Kingdom
Guy's and St Thomas' NHS Foundation Trust, Guy's HospitalRecruiting
London, United Kingdom
The Royal Marsden NHS Foundation TrustNot Yet Recruiting
London, United Kingdom
The Christie NHS Foundation TrustNot Yet Recruiting
Manchester, United Kingdom
Oxford University Hospitals NHS Foundation Trust, Churchill HospitalNot Yet Recruiting
Oxford, United Kingdom
University of Southampton NHS Foundation Trust, Southampton General HospitalNot Yet Recruiting
Southampton, United Kingdom