NIVOLUMAB for Localized melanoma | Resectable stage III cutaneous or mucosal melanoma

Inclusion criteria

• {"criterion_text":"- NEOREM_Age≥ 12 years with at least 40kg body weight or otherwise as per specified in subprotocol.\n- NEOREM_Patient affiliated to the French social security regimen.\n- NEOREM_Patients with mental and legal ability to fully consent for undergoing the exploratory procedures (blood draws and biopsies) prior and upon treatment (at baseline PORTRAIT and once on-treatment PORTRAIT).\n- NEOREM_Patient is willing and able to comply with the protocol for the duration of the trial including undergoing treatment and scheduled visits, and examinations including follow-up.\n- NEO-1_Patients with age ≥ 18 years\n- NEO-1_Patients with resectable and measurable (according to RECIST v1.1 criteria) stage III cutaneous or mucosal melanoma.\n- NEO-1_Patients who received anti-PD-1 and stopped treatment > 6 months prior to their inclusion in NEO-1 trial are eligible.\n- NEO-1_Patients who received target therapy and stopped treatment > 3 months prior to their inclusion in NEO-1 trial are eligible.\n- NEOREM_Prior to the inclusion in the NEOREM master protocol, patients must have signed a written informed consent to baseline PORTRAIT profiling.\n- NEOREM_Localized solid malignancy that is eligible to receive neo-adjuvant therapy and has medical unmet needs related to disease-free survival, overall survival or quality of life\n- NEOREM_ Having a measurable disease (i.e. at least one measurable lesion according to RECIST v1.1 for solid tumors\n- NEOREM_Eastern cooperative oncology group (ECOG) performance status between 0 and 2.\n- NEOREM_Patients amenable to undergo blood draw and tumor biopsy procedures.\n- NEOREM_Adequate organ function as defined by the following criteria: • Total bilirubin ≤1.5 ULN, or ≤3.0 ULN in participants with Hepato-Cellular Carcinoma (HCC) or known Gilbert’s syndrome if the increase is predominantly due to unconjugated bilirubin. • ALT ≤ 3 x ULN; if liver metastases ALT ≤ 5 x ULN • Absolute Neutrophils count (ANC) ≥ 1000 cells/mm³ in the absence of G-CSF or GM-CSF within ≤2 weeks before the first dose of study treatment. • Platelets ≥100 000 cells/mm³ • Hemoglobin ≥ 9.0 g/dL • Albumin ≥ 30 g/L • Calculated creatinine clearance ≥50 mL/min/1.73 m2\n- NEOREM_Women of childbearing potential (WOCBP) must have a negative serum or urine pregnancy test within 7 days prior to initiation of treatment.\n- NEOREM_Both sexually active WOCBP and male (and their WOCBP partners) patients must agree to use two methods of effective contraception, one of them being a physical barrier method, or to abstain from sexual activity during the study and for the period indicated in specific sub-protocol after the last study drug administration."}

Exclusion criteria

• {"criterion_text":"- NEOREM_Cancer patients with advanced stages and/or distant metastasis (unless curable oligometastatic disease). Some sub-protocols could enroll patients with loco-regional (N+) stages amenable to curative intention strategies.\n- NEOREM_Administration of a live, attenuated vaccine within 4 weeks prior to enrolment\n- NEOREM_ Radiotherapy to the chosen RECIST target lesion(s) (unless a progression after radiotherapy has been documented).\n- NEOREM_Treatment with other investigational drugs or treatment in another clinical trial within the past 4 weeks before start of therapy or concomitantly with the trial.\n- NEOREM_ Persistence of a clinically relevant treatment-related toxicity from previous chemotherapy, targeted therapy and/or local treatments which could hamper the safety or efficacy assessment of the therapy tested (for previous disease).\n- NEOREM_Patients with evolving tumors next to cavitary or major blood vessels at high risk of massive bleeding and/or perforation.\n- NEO-1_Patients with clinically or radiologically detectable distant metastases.\n- NEO-1_Patients with uveal melanoma\n- NEOREM_Major injuries and/or surgery within the past 4 weeks prior to start of study treatment with incomplete wound healing and/or planned major surgery during the on-treatment study period\n- NEOREM_History of clinically significant hemorrhagic or thromboembolic event in the past 3 months.\n- NEOREM_History of significant cardiovascular diseases (i.e. supraventricular tachycardia, uncontrolled hypertension, unstable angina, history of infarction within the past 12 months prior to start of study treatment, congestive heart failure > NYHA II, serious cardiac arrhythmia, pericardial effusion).\n- NEOREM_Pregnancy or breastfeeding.\n- NEOREM_Ongoing uncontrolled endocrinopathy. Ancient endocrinopathy currently stable with substitutive therapy should not be excluded from the trial.\n- NEOREM_Other malignancies within the past 5 years other than basal cell skin cancer or carcinoma in situ of the cervix. A history of more than 3 years of local prostate cancer treated by surgery and without PSA elevation since surgery, or local breast carcinoma treated by surgery without relapse or resected non-muscle invasive bladder cancers are eligible.\n- NEOREM_Active serious infections in particular if requiring systemic antibiotic or antimicrobial therapy. A wash out of more than 3 weeks is required after last systemic antibiotics to allow reconstitution of the microbiome. Patients infected by HIV but having efficient anti-retroviral therapy and CD4+ T-cell counts >500/mm³ are eligible. Patients with a history of HBV or HCV that are cured and have eligible liver function criteria are also eligible.\n- NEOREM_Gastrointestinal disorders or abnormalities that would interfere with absorption of the study drug in case an oral drug is tested in the sub-protocol for which the patient is screened.\n- NEO-1_Patients with any hypersensitivity to the active ingredient or to any of the excipients of nivolumab and/ ipilimumab.\n- NEO-1_Patients without pathological evaluable disease according to RECIST v1.1 criteria.\n- NEOREM_Intake of Ganoderma Lucidum mushroom (also called “Reishi”) and/or herbal remedies and/or traditional medicines within the past weeks prior to start of study treatment or concomitantly with the trial because of their potential to increase treatment related adverse events.\n- NEOREM_Any life-threatening allergy to one of the experimental products tested in the subprotocol where the patient is eligible. In case of allergy to contrast media, patient monitoring should be performed with alternate methods (both CT-scan or MRI).\n- NEOREM_Any psychological, familial, sociological, geographical factors, lifestyle, behavior, clinical or biological parameters or elements in the past medical history of the patients that, according to the investigator, could preclude the ability of the trial to directly reach its objectives, or indirectly via treatment observance or study follow up. Patients with active alcoholism and/or drug abuse are excluded.\n- NEOREM_Person deprived of its liberty or under protective custody or guardianship\n- NEOREM_History of life threatening autoimmune/immune mediated inflammatory disease, including but not limited to severe colitis, pneumonitis, Guillain-Barré syndrome, antiphospholipid syndromes and myocarditis. Patients with a history of auto-immune endocrinopathy (hypo/hyper thyroiditis, type 1 diabetes mellitus, …) and who are stable on hormone replacement therapy are eligible for the study. Patients with a history of vitiligo, alopecia areata, cutaneous psoriasis and grade 1-2 Sjogren syndrome are eligible\n- NEOREM_Treatment with systemic long-term immunosuppressive medications unless otherwise specified in the specific therapeutic sub-protocols. Those immunosuppressive drugs must have been stopped at least 4 weeks prior to enrolment. Hormone replacement therapy with physiological doses of hydrocortisone is acceptable.\n- NEOREM_Chemotherapy, hormonotherapy, radiotherapy or immunotherapy or therapy with monoclonal antibodies or small tyrosine kinase inhibitors within the past 4 weeks or 5 half-life times (whatever the shortest) prior to treatment with the trial drugs."}

Primary endpoints

• {"endpoint_text":"- NEO-1_The primary efficacy endpoint is defined as a pathological complete response (pCR) rate defined as the percentage of patients with pCR defined as the complete absence of viable tumor cells, or the major pathologic response (MPR) defined as less than 10% of surviving tumor cells in tumor biopsy of the surgical specimen.","definition_or_measurement_approach":"pCR defined as complete absence of viable tumor cells; MPR defined as less than 10% of surviving tumor cells in tumor biopsy of the surgical specimen."}
• {"endpoint_text":"- NEO-1_The primary safety endpoint defined as the percentage of patients whose surgery was delayed by more than 4 weeks beyond the planned timeline, due to treatment-related adverse events.","definition_or_measurement_approach":"Percentage of patients whose surgery was delayed by >4 weeks beyond planned timeline due to treatment-related adverse events."}

Secondary endpoints

• {"endpoint_text":"- NEO-1_Objective Response Rate (ORR), defined as the proportion of patients achieving complete response (CR) or partial response (PR) as assessed by the investigator according to RECIST v1.1.","definition_or_measurement_approach":"ORR = proportion with CR or PR as assessed by investigator per RECIST v1.1."}
• {"endpoint_text":"- NEO-1_Durable Clinical Benefit (DCB), defined as patient alive and without disease progression (complete response [CR] + partial response [PR] + stable disease [SD]) according to RECIST v1.1 at 6 weeks.","definition_or_measurement_approach":"DCB = patient alive and without disease progression (CR+PR+SD) per RECIST v1.1 at 6 weeks."}
• {"endpoint_text":"- NEO-1_Overall Survival (OS), defined as the time from inclusion until death from any cause. Patients who are alive at last follow-up news will be censored at this date.","definition_or_measurement_approach":"OS = time from inclusion until death from any cause; censor at last follow-up if alive."}
• {"endpoint_text":"- NEO-1_Recurrence-free survival (RFS), defined as the length of time from surgery until evidence of cancer recurrence or death of any cause, whichever occurs first.","definition_or_measurement_approach":"RFS = time from surgery until cancer recurrence or death, whichever first."}
• {"endpoint_text":"- NEO-1_Distant metastasis-free survival (MFS), defined as the length of time from inclusion until evidence of distant metastases or death of any cause, whichever occurs first.","definition_or_measurement_approach":"MFS = time from inclusion until evidence of distant metastases or death, whichever first."}
• {"endpoint_text":"- NEO-1_Safety will be evaluated according to the incidence of adverse events (AEs) graded by the National Cancer Institute - common terminology criteria for adverse events NCI-CTCAE v5.0.","definition_or_measurement_approach":"Safety = incidence of AEs graded by NCI-CTCAE v5.0."}
• {"endpoint_text":"- NEO-1_Health-related quality of life will be evaluated through the EORTC QLQ-C30 questionnaire by collecting data at baseline and at each investigational medical product (IMP) administration cycle during the neo-adjuvant treatment period, at surgery and during the first year of the follow-up period (M1, M3, M6, M12).","definition_or_measurement_approach":"HRQoL measured using EORTC QLQ-C30 at baseline, each IMP administration cycle, at surgery and at M1, M3, M6, M12 during first year follow-up."}

France

Earliest CTIS Part Ii Submission Date

08-10-2025

Latest Decision Or Authorization Date

28-10-2025

Processing Time Days

20

Number Of Sites

5

Number Of Participants

50

Primary sponsor

Full Name

Unicancer

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

France

Third parties

• {"country":"France","full_name":"Creapharm Clinical Supplies","duties_or_roles":"sponsorDuties code 14","organisation_type":"Pharmaceutical company"}