Open Actively Recruiting

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

About

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.

Primary Purpose

Treatment

Study Type

Interventional

Phase

Phase 2

Eligibility

Gender

All

Healthy Volunteers

Minimum Age

18 Years

Maximum Age

N/A

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