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)

Description
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/

Objective
Primary: To evaluate the efficacy of IMA203 compared with control (investigators choice)
Secondary: To evaluate the efficacy of IMA203 compared with control (investigators choice)
To evaluate the efficacy of IMA203 compared with control (investigators choice)
To evaluate safety and tolerability of IMA203 compared with control (investigators choice)
To evaluate the patient-reported quality of life before and after treatment with IMA203 compared with control (investigators choice)

Treatment 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).

Key Eligibility 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.

Applicable Disease Sites
Melanoma/Skin cancer

Participating Institutions
UW Health Eastpark Medical Center; UW Health University Hospital