SUPRAME - ACTengine® IMA203 vs. investigator’s choice of treatment in previously treated, unresectable or metastatic cutaneous melanoma

Phase 3

Recruiting

• Conditions: melanoma, cutaneous malignant

• Registration Number: 2024-517062-42-00
• Lead Sponsor: Immatics US Inc.

Brief Summary

To evaluate the efficacy of IMA203 compared with control (investigator’s choice)

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).

Study Timeline

• Study First Submitted: 2024-12-11
• Study First Submitted QC: 2024-12-16
• Study First Posted: 2024-12-19
• Study Start: 2025-01-14
• Status Verified: 2025-07
• Last Update Submitted: 2025-07-25
• Last Update Posted: 2025-07-28
• Primary Completion: 2028-01
• Study Completion: 2031-10-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: Not specified
• Target Recruitment: 84

Inclusion Criteria

Patients ≥ 18 years of age

Eastern Cooperative Oncology Group (ECOG) performance status 0 to 1

Confirmed HLA status

Adequate renal, hepatic and pulmonary function, acceptable coagulation status, adequate organ and marrow function

Measurable disease according to RECIST 1.1

Pathologically confirmed and documented cutaneous melanoma, CM patients with unresectable or metastatic (= advanced) disease who must have disease progression (resistance, toxicity) on or after at least one PD-1 inhibitor

Patients with BRAF mutation should have been treated with one prior line of BRAF-directed therapy unless deemed not clinically indicated at Investigator’s discretion due to concurrent medical condition, prior toxicity, or if declined by the patient

The patient must have recovered from any side effects of prior therapy to grade 1 or lower prior to randomization, and prior to LD and subsequent treat-ment

Exclusion Criteria

Primary mucosal or uveal melanoma and melanoma of unknown primary

History of other malignancies within the last 3 years

Patients with prior allogenic stem-cell transplantation or solid-organ transplantation

The patient is pregnant or is breastfeeding.

History of hypersensitivity to treatment in the IMA203 arm or rescue medications or presence of any contraindications and other limitations for planned treatment with investigator’s choice

Any condition contraindicating leukapheresis

The patient has concurrent severe and/or uncontrolled medical disease. Any other condition that would, in the investigator’s judgement, contraindicate the patient’s participation in the clinical trial because of safety concerns or com-pliance with clinical trial procedures

Patients with active brain metastases or leptomeningeal metastases at VA/VB

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Progression-free survival (PFS), centrally assessed by a Blinded Independent Central Review (BICR) using RECIST 1.1		Progression-free survival (PFS), centrally assessed by a Blinded Independent Central Review (BICR) using RECIST 1.1

Secondary Outcome Measures

Name	Time	Method
Overall survival (OS)	up to 5 years post first treatment of last patient	conducted onsite or can be performed by phone
Objective response rate (ORR)	up to 5 years post first treatment of last patient	complete responses (CR) and partial response (PR) based on best overall response (BOR), locally and centrally (by blinded independent central review) assessed using RECIST 1.1
Progression-free survival	up to 5 years post first treatment of last patient	Progression-free survival locally assessed using RECIST 1.1
Treatment-emergent adverse events (TEAEs)	until 85 days after cell therapy treatment or 30 days after last treatment	To evaluate safety and tolerability of treatment with IMA203 compared with control (investigator's choice)
Adverse events of special interest (AESIs)	until 85 days after cell therapy treatment or 30 days after last treatment	To evaluate safety and tolerability of treatment with IMA203 compared with control (investigator's choice)
Treatment-emergent serious adverse events (TESAEs)	until 85 days after cell therapy treatment or 30 days after last treatment	To evaluate safety and tolerability of treatment with IMA203 compared with control (investigator's choice)
Frequency and duration of dose interruptions, reductions, and discontinuations	up to 5 years post first treatment of last patient	To evaluate safety and tolerability of treatment with IMA203 compared with control (investigator's choice)
EORTC QLQ-C30	up to 5 years post first treatment of last patient	To evaluate the patient-reported quality of life before and after treatment with IMA203 compared with control (investigator's choice)
EQ-5D-5L	up to 5 years post first treatment of last patient	To evaluate the patient-reported quality of life before and after treatment with IMA203 compared with control (investigator's choice)

Trial Locations

Locations (30)

Honor Health Research Institute; 🇺🇸 Scottsdale, Arizona, United States

City of Hope National Medical Center; 🇺🇸 Duarte, California, United States

UCLA Hematology/Oncology; 🇺🇸 Los Angeles, California, United States

Stanford Cancer Center; 🇺🇸 Stanford, California, United States

Yale Cancer Center; 🇺🇸 New Haven, Connecticut, United States

Moffitt Cancer Center; 🇺🇸 Tampa, Florida, United States

Massachusetts General Hospital; 🇺🇸 Boston, Massachusetts, United States

Laura and Isaac Perlmutter Cancer Center at NYU Langone Health; 🇺🇸 New York, New York, United States

Memorial Sloan Kettering Cancer Center; 🇺🇸 New York, New York, United States

UNC Hospitals, The University of North Carolina at Chapel Hill; 🇺🇸 Chapel Hill, North Carolina, United States

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