NIVOLUMAB for Stage III melanoma

Inclusion criteria

• {"criterion_text":"- Participants must be at least 18 years of age.\n- No prior targeted therapy targeting BRAF and/or MEK.\n- Can provide a signed informed consent as described in the protocol, including compliance with the requirements and restrictions listed in the ICF and in this protocol.\n- World Health Organization (WHO) Performance Status 0 or 1.\n- Patients must have a.\tHistologically or cytologically confirmed Stage III melanoma. In the case of in-transit metastases (with or without lymph node metastases)‚ ≤3 resectable in-transit metastases are allowed. b.\tPatients with cutaneous, acral, or unknown primary melanomas are eligible for enrollment. c.\tResectable tumors are defined as having no significant vascular, neural or bony involvement. Only patients where a complete surgical resection with tumor-free margins can safely be achieved are defined as resectable.\n- Female patient of childbearing potential should have a negative urine or serum pregnancy test within 72 hours prior to receiving the first treatment. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.\n- Female patients of childbearing potential must be willing to use a highly effective method of contraception, for the course of the study through 150 days after the last dose of study medication. Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject. Highly effective methods of contraception include one or more of the following: a.\tmale partner who is sterile (vasectomised) prior to the female study subject’s entry into the study and is the sole sexual partner for the female subject; b.\thormonal (oral, intravaginal, transdermal, implantable or injectable) c.\tan intrauterine hormone-releasing system (IUS) d.\tan intrauterine device (IUD) with a documented failure rate of < 1%.\n- Male patients of childbearing potential must agree to use an adequate method of contraception, starting with the first dose of study therapy through 150 days after the last dose of study therapy. Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject. A unique female sexual partner must postmenopausal, permanently sterilized (e.g. hysterectomy or tubal ligation), or use a highly effective method of contraception.\n- No other malignancies, except if treated with curative intent and with a cancer-related life expectancy of more than 5 years.\n- No prior immunotherapy targeting CTLA-4, PD-1 or PD-L1."}

Exclusion criteria

• {"criterion_text":"- Unresectable melanoma\n- Uveal/ocular or mucosal melanoma\n- Any serious or uncontrolled medical conditions that, in the investigator's opinion, may increase the risk associated with study participation or study drug administration, impair the ability of the subject to receive protocol therapy (including operation), or interfere with the interpretation of study results\n- Subjects with a condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of study drug administration. Inhaled or topical steroids and adrenal replacement doses > 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease.\n- Women who are pregnant or breastfeeding.\n- Any condition that potentially hamper compliance with the study protocol and follow-up schedule; those conditions should be discussed with the subject before registration in the trial."}

Primary endpoints

• {"endpoint_text":"- Event-free survival (EFS), defined as time from randomization to melanoma progression (irresectable stage III or stage IV disease), melanoma recurrence, or death from any cause (treatment-related, melanoma related or any other).","definition_or_measurement_approach":"EFS defined as time from randomization to melanoma progression (irresectable stage III or stage IV disease), melanoma recurrence, or death from any cause (treatment-related, melanoma related or any other)."}

Secondary endpoints

• {"endpoint_text":"- Relapse-free survival (RFS), defined as time between date of surgery and date of melanoma recurrence, treatment-related death or melanoma-related death, whichever occurs first.","definition_or_measurement_approach":"RFS defined as time between date of surgery and date of melanoma recurrence, treatment-related death or melanoma-related death, whichever occurs first."}
• {"endpoint_text":"- Distant metastasis-free survival (DMFS), defined as time between date of randomization and date of first distant metastasis, treatment-related death or melanoma-related death, whichever occurs first.","definition_or_measurement_approach":"DMFS defined as time between date of randomization and date of first distant metastasis, treatment-related death or melanoma-related death, whichever occurs first."}
• {"endpoint_text":"- Overall survival (OS), defined as time between date of randomization and date of death.","definition_or_measurement_approach":"OS defined as time between date of randomization and date of death."}
• {"endpoint_text":"- Major pathological response (MPR) (≤10% viable tumor cells), difference in MPR between combined ICI and monotherapy, central review of all surgical specimens by three expert melanoma pathologists.","definition_or_measurement_approach":"MPR defined as ≤10% viable tumor cells; assessment by central review of surgical specimens by three expert melanoma pathologists; comparison of MPR rates between arms."}
• {"endpoint_text":"- Correlation of pathologic response in each arm to RFS, DMFS, and OS.","definition_or_measurement_approach":"Correlation analyses between pathologic response and time-to-event endpoints RFS, DMFS, and OS."}
• {"endpoint_text":"- Correlation of radiological and clinical response evaluation to RFS, DMFS, and OS.","definition_or_measurement_approach":"Correlation analyses between radiological/clinical response evaluations and RFS, DMFS, and OS."}
• {"endpoint_text":"- Proportion of patients having surgery according to plan (within 10 weeks from first neoadjuvant course).","definition_or_measurement_approach":"Proportion metric: patients who undergo planned surgery within 10 weeks from first neoadjuvant course."}
• {"endpoint_text":"- Surgical complication rates according to Clavien-Dindo surgical classification.","definition_or_measurement_approach":"Surgical complications categorized and reported according to Clavien-Dindo classification."}
• {"endpoint_text":"- Frequency and duration of all grade and grade 3-5 treatment-related adverse events (AEs) according to CTCAE 5.0.","definition_or_measurement_approach":"Adverse events graded per CTCAE v5.0; frequency and duration of all-grade and grade 3-5 treatment-related AEs will be reported."}

Sweden

Earliest CTIS Part Ii Submission Date

08-04-2025

Latest Decision Or Authorization Date

05-05-2025

Processing Time Days

27

Number Of Sites

3

Number Of Participants

128

Primary sponsor

Full Name

Karolinska University Hospital

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

Sweden