IRB Study Number 25-300
Status Recruiting
Phase Phase 3
Location Cleveland Clinic Main Campus
Institute Taussig Cancer Institute
Description
Primary Objectives
• To evaluate the efficacy of IMA203 compared with control (investigator’s choice)
Secondary Objectives
• To evaluate safety and tolerability of IMA203 compared with control (investigator’s choice)
• To evaluate the patient-reported quality of life before and after treatment with IMA203 compared with control (investigator’s choice)
Inclusion Criteria
1 Patient must have voluntarily signed and dated a written ICF, be able to understand and comply with clinical trial procedures.
2 Patient must have pathologically confirmed and documented cutaneous melanoma. CM patients (including acral melanoma) with unresectable or metastatic (= advanced) disease, per the AJCC staging system (8th edition), are allowed to start screening.
3 Patients ≥ 18 years old
4 HLA type: HLA-A*02:01 positive Note: Patient may enter screening procedures for HLA-A*02:01 at any time after the diagnosis of unresectable or metastatic disease. Note: US patients undergo HLA testing as a trial-specific procedure by Immatics’ designated US central laboratory. EU patients undergo HLA testing as a trial-specific procedure using a CE-marked assay with a 2- field/4-digit resolution at a local laboratory that is compliant with local national provisions, followed by a (potentially post-treatment) re-confirmation at Immatics’ designated central laboratory at any time after treatment start. (see further details in Section 8.2.1).
5 The patient has adequate pulmonary function. Confirm that serious pulmonary dysfunction, that in the judgement of the investigator would compromise the patient’s ability to tolerate protocol therapy or significantly increase the risk for complications does not exist Note: To be performed before tumor biopsy (if applicable), if the investigator has doubts that the patient meets the eligibility criteria for pulmonary function test. If no biopsy is performed, test must be performed before completion of VA.
6 ECOG Performance Status of 0 to 1
7 The patient has adequate organ and marrow function, absolute neutrophil count (ANC) ≥ 1.0 x 109/L (without granulocyte colony-stimulating factor [G-CSF] support); platelets ≥ 75,000/μL; hemoglobin ≥ 8 g/dL (repeat assessment allowed)
8 Acceptable coagulation status: international normalized ratio (INR) of prothrombin time (PT) of blood coagulation ≤ 2 x the upper limit of normal (ULN) and partial thromboplastin time (PTT) or activated PTT (aPTT) ≤ 2 x ULN (repeat assessment allowed)
9 The patient has adequate hepatic function, as defined by a total bilirubin level ≤ 1.5 x ULN unless the patient has known Gilbert's syndrome, and alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 x ULN or ≤ 5 x ULN for patients with liver tumor lesions (repeat assessment allowed)
10 Adequate renal function defined by serum creatinine clearance ≥ 50 mL/min (as estimated by Cockcroft Gault formula; repeat assessment allowed)
11 Leukapheresis needs to be available prior to submission of TRF. HLA-A*02:01 positive patients with unresectable or metastatic CM may undergo leukapheresis, if anticipated that patient will receive trial treatment at latest during the next 9 to 12 months.
12 Submitted TRF. Note: Upon acknowledgment patients will be randomized and for patients randomized to the experimental arm, IMA203 manufacturing will be initiated. Start date of IMA203 manufacturing will be indicated on the TRF.
13 Unresectable or metastatic CM patients who must have 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 disease. Patients should be considered for anti-PD-1/anti-CTLA-4 combination therapy prior to initial eligibility assessment. PD on or after at least one PD-1 inhibitor applied either as monotherapy or in combination with other immunotherapies must be confirmed at VB as summarized by Kluger et al. (Kluger et al., 2023; Kluger et al., 2020), if this is the last prior treatment line before this clinical trial. This determination is made by the investigator. There is no limitation on the number or kind of prior treatment lines.
14 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.
15 Life expectancy > 6 months X
16 Patients must have measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST 1.1) measured on CT or MRI Note: Locally treated or irradiated lesions are not measurable lesions, unless there has been demonstrated progression in the lesion. Note: Recently biopsied lesions or lesions planned to be resected for TIL production are not measurable lesions.
17 Female patients of childbearing potential must use adequate contraception (see Appendix 13.1) from randomization until 12 months after the infusion of IMA203 (in the experimental arm) or in line with the instructions provided for investigator’s choice treatment (in the control arm)
18 Male patients must agree to use effective contraception or be abstinent while on trial and for 6 months after the infusion of IMA203 (in the experimental arm) or in line with the instructions provided for investigator’s choice treatment (in the control arm)
19 The patient must have recovered from any side effects of prior therapy to grade 1 or lower (except for nonclinically significant toxicities, e.g., alopecia, vitiligo) prior to randomization, and prior to LD and subsequent IMA203 treatment, control arm treatment or bridging therapy. As determined by the investigator, the patient may still be eligible, if the patient has not fully recovered from grade ≥ 2 toxicities, if these toxicities are not anticipated to further improve (e.g., chronic neuropathy) and such toxicities are not anticipated to worsen with the LD and subsequent IMA203 treatment, control arm treatment or bridging therapy.
Exclusion Criteria
1 Primary mucosal or uveal melanoma and melanoma of unknown primary X
2 History of other malignancies (except for adequately treated basal or squamous cell carcinoma or carcinoma in situ) within the last 3 years
3 Patients with serious autoimmune disease, including patients with a history of active serious inflammatory bowel disease (including Crohn's disease and ulcerative colitis) and autoimmune disorders such as rheumatoid arthritis, multiple sclerosis, systemic progressive sclerosis (scleroderma), systemic lupus erythematosus or autoimmune vasculitis (e.g., Wegener's granulomatosis) Note: At the discretion of the investigator, these patients may be included if their disease is well controlled without the use of immunosuppressive agents
4 The patient is known to have, based on prior history and physical exam, any of the following cardiac conditions: uncontrolled hypertension despite optimal therapy, uncontrolled angina, ventricular arrhythmias, congestive heart failure (New York Heart Association Class 2 or above), baseline left ventricular ejection fraction ≤ 50%, prior or current cardiomyopathy, atrial fibrillation with heart rate > 100 bpm, reoccurrence of pericardial effusion within previous 4 weeks, unstable ischemic heart disease (myocardial infarction within 6 months prior to leukapheresis or angina requiring use of nitrates more than once weekly)
5 Patients with prior allogenic stem-cell transplantation or solid-organ transplantation
6 The patient has concurrent severe and/or uncontrolled medical disease that could compromise participation in the trial (e.g., uncontrolled diabetes, severe infection requiring active treatment, severe malnutrition, chronic severe liver, or renal disease)
7 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.
8 Patients with known hypersensitivity to any of the rescue medications, if there is only one rescue medication or the patient is sensitive to all in a group X X
9 History of or current immunodeficiency disease or prior treatment compromising immune function at the discretion of the investigator
10 Patient is known to be positive for HIV, or patient with known active hepatitis B or C virus infection
11 Any condition contraindicating leukapheresis
12 The patient is pregnant (confirmed by serum or urine pregnancy test) or is breastfeeding (test at S3 to be performed only, if prior test is >30 days ago; test at VB must be completed within 7 days prior to TD-6)
13 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).
14 The patient has received systemic corticosteroids (≥ 10 mg/day prednisone or equivalent) within 2 weeks prior to leukapheresis. The patient has received surgery or other anti-cancer therapies, including checkpoint inhibitors, targeted therapies, chemotherapy, any agent that is likely to suppress bone marrow function, or investigational medicinal products within 7 days prior to leukapheresis.
15 Patients with any active infection or ongoing reactivation of infection (e.g., herpes simplex virus, Epstein-Barr virus [EBV], cytomegalovirus [CMV], COVID-19, influenza, Severe Acute Respiratory Syndrome [SARS], recent sepsis) within the last 3 weeks. For patients fully recovered from infections, screening/eligibility assessment may start or continue.
16 Patients who underwent non-myeloablative lymphodepletion prior to cell therapy within the last 6 months
17 Prior treatment with IMA203
18 Patients with ascites, pleural or pericardial effusion which requires repeated (2 within 4 weeks) or continuous paracentesis, thoracentesis or pericardiocentesis within last 2 months
19 Patients with LDH > 2.0 x ULN
20 Patients with LDH > 3.0 x ULN
21 Concurrent treatment in another clinical trial or a device study that could interfere with the IMA203 treatment or planned investigator’s choice treatment
22 Patients with active brain metastases or leptomeningeal metastases at VA Note: Patients with a history of brain metastases are eligible, if imaging studies performed ≥4 weeks following treatment indicate stable disease, the patient is asymptomatic, and steroid therapy has been discontinued for ≥2 weeks. Patients with signs or symptoms of brain metastases are not eligible unless brain metastases were ruled out by MRI scans. Note: Patients with active brain metastases may pause at this point in the trial and undergo adequate treatment for brain metastases. They may continue with screening procedures thereafter, once brain metastases are confirmed to be inactive as defined above.
23 Patients with active brain metastases or leptomeningeal metastases at VB Exception: Patients with asymptomatic, previously untreated brain metastases may continue in the trial provided there are ≤ 3 total lesions in the brain and the longest diameter of each lesion is < 1cm. Stability of these lesions does not need to be confirmed by repeat imaging. Note: Patients not eligible according to these exclusion criteria (e.g., > 3 total lesions, the longest diameter of a single lesion ≥ 1 cm) may nevertheless be treated in a separate exploratory side-arm cohort (please refer to Section 5.3.2).
24 The patient, in the judgment of the investigator, is not able to tolerate LD, low dose IL-2 IMA203 or planned investigator’s choice treatment. X X
25 The patient has received any investigational therapies, inactivated vaccines, chronic use of systemic corticosteroids (≥ 10 mg/day prednisone or equivalent) or IV antibiotics within 1 week prior to randomization, or live vaccines within 4 weeks prior to randomization. Patients must have completed any major surgery at least 4 weeks prior to randomization and must have recovered or stabilized from the side effects of prior surgery.
26 The 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 (experimental and control arm treatment).
