Recruiting

Phase 3

IMA203 vs. Investigator's ChoiceSUPRAME-ACTengine® IMA203 vs. Investigator's Choice of Treatment in Previously Treated, Unresectable or Metastatic Cutaneous Melanoma

Sponsor:

Immatics US, Inc.

Code:

NCT06743126

Conditions

Melanoma, Cutaneous Malignant

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

IMA203

nivolumab plus relatlimab

lifileucel

nivolumab

pembrolizumab

Study Details

Brief 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/

Conditions

Melanoma, Cutaneous Malignant

Study ID

NCT06743126

Start date

Jan 14, 2025

Status verified date

Jun, 2026

Completion date

Oct, 2031

Anticipated

Primary completion date

Jan, 2028

Anticipated

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

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 Design

Enrollment

360 participants

Anticipated

Allocation

Randomized

Intervention Model

Parallel Assignment

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Experimental arm

Non-myeloablative chemotherapy for lymphodepletion (LD) over 4 days using fludarabine (FLU) and cyclophosphamide (CY), 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

active comparator: Control arm- investigator's choice

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), optional bridging therapy.

Interventions

IMA203

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

nivolumab plus relatlimab