Pembrolizumab for Melanoma

Inclusion criteria

• {"criterion_text":"- ≥18 years of age on the day of signing informed consent.\n- Capable of providing documented informed consent, which includes compliance with the requirements and restrictions listed in the ICF and in this protocol. Participants (or legally acceptable representative) must provide documented informed consent\n- Histologically confirmed high risk primary cutaneous pT1b-4b melanoma. High risk primary melanoma is defined in this study as the following AJCC8 T-stages: •\tpT1b-3a, with a poor prognostic score on the Merlin™ test (“Merlin™ high risk”); •\tpT3b-4b, irrespective of their Merlin™ test result\n- Amenable to sentinel lymph node biopsy.\n- No evidence of metastatic dissemination as demonstrated by PET/CT, ultrasound of the draining lymph node basin, and clinical examination.\n- No prior exposure to systemic treatment for melanoma.\n- Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 0, 1 or 2 assessed within 7 days prior to the first dose of study treatment.\n- Adequate organ function as defined: Absolute neutrophil count ≥ 1.2 x 103/mm3, Hemoglobin ≥ 9.0 g/dL, Platelet count ≥ 75 x 103/mm3, Total bilirubin ≤ 1.5 x ULN, ALT ≤ 2.5 x ULN, Calculated creatinine clearance ≥ 50 mL/min). Specimens must be collected within 7 days prior to the start of study treatment.\n- Women: a.\tNot a woman of childbearing potential (WOCBP) b.\tWomen of childbearing potential must have a negative serum pregnancy test during screening and within 72 hours prior to treatment initiation and agree to use effective contraception of their choice throughout the treatment period, and for 16 weeks after the last dose of study treatment. c.\tWomen who are not breastfeeding\n- Men with a female partner of childbearing potential must agree to use effective contraception from 14 days prior to administration of the first dose of study treatment or have either had a prior vasectomy, throughout the treatment period, and for 16 weeks after the last dose of study treatment."}

Exclusion criteria

• {"criterion_text":"- Patients with uveal melanoma and melanoma of unknown primary origin.\n- Prior transplantation of human cells, tissues and organs (e.g. liver transplant) or candidates for any type of transplantation.\n- History or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the patient’s participation for the full duration of the trial, or is not in the best interest of the patient to participate, in the opinion of the treating investigator.\n- Known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.\n- Any contra-indication for evaluation by whole body 18F-FDG-PET/CT or MRI.\n- Active autoimmune disease requiring systemic treatment\n- Patients with a history of previous malignancies (except non-melanoma skin cancers, and the following in situ cancers: gastric, colon, cervical/dysplasia, melanoma, or breast) are excluded unless a complete remission was achieved at least 3 years prior to screening and no additional therapy is required or anticipated to be required during the study period.\n- Known Human Immunodeficiency Virus (HIV), hepatitis B virus (HBV), or hepatitis C virus (HCV) infection. Exception: subjects with laboratory evidence of cleared HBV and HCV infection will be permitted.\n- Any serious or unstable pre-existing medical conditions (aside from malignancy exceptions specified above), psychiatric disorders, or other conditions that could interfere with the subject’s safety, obtaining informed consent, or compliance with study procedures.\n- Active infection at the time of screening (e.g. wound infection)\n- Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to the study treatment, or excipients\n- History of organ allograft.\n- Patients who have previously been exposed to checkpoint inhibitors"}

Primary endpoints

• {"endpoint_text":"- The rate of negative sentinel node procedures (=absence of viable melanoma metastases found on histopathological examination of the sentinel node) following the neoadjuvant treatment.","definition_or_measurement_approach":"Negative sentinel node procedure defined as absence of viable melanoma metastases found on histopathological examination of the sentinel node."}

Secondary endpoints

• {"endpoint_text":"- RFS is defined as the time from study recruitment to the date of first recurrence (or death from any cause), DMFS from recruitment to the first diagnosis of a distant metastasis (or death from any cause) and OS is defined as the time of recruitment until the date of death from any cause.","definition_or_measurement_approach":"RFS, DMFS and OS measured as time-to-event from recruitment to recurrence/distant metastasis/death respectively; events include death from any cause where specified."}
• {"endpoint_text":"- Safety as assessed by anamnesis, clinical examination, analysis of blood and any additional medical examination that is indicated. AE will be graded by the Common Terminology Criteria of Adverse events (CTCAE), version 5.0 (National Institutes of Health, National Cancer Institute).","definition_or_measurement_approach":"Safety assessed via clinical exam, labs, other indicated exams; adverse events graded per CTCAE v5.0."}
• {"endpoint_text":"- Health-related quality of life through the following patient-reported outcomes measure (PROM): European Organization for Research and Treatment of Cancer Quality of Life Questionnaire C30 (EORTC-QLQ-C30).","definition_or_measurement_approach":"HRQoL measured using EORTC-QLQ-C30 PROM instruments completed by participants per schedule."}
• {"endpoint_text":"- Describe markers of pathological response of melanoma micrometastasis in the sentinel node.","definition_or_measurement_approach":"Pathological response markers described from histopathological examination of sentinel node micrometastases."}
• {"endpoint_text":"- Describe the relation between the gene expression signature in bulk RNA sequencing of the primary tumor and the result of the sentinel node biopsy.","definition_or_measurement_approach":"Relation explored by comparing gene expression signature from bulk RNA sequencing of primary tumor tissue with sentinel node biopsy results."}

Belgium

Earliest CTIS Part Ii Submission Date

17-02-2025

Latest Decision Or Authorization Date

14-10-2025

Processing Time Days

239

Number Of Sites

1

Number Of Participants

49

Primary sponsor

Full Name

UZ Brussel

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

Belgium

Third parties

• {"country":"","full_name":"MERCK SHARP & DOHME B.V.","duties_or_roles":"Marketing authorisation holder / product manufacturer (KEYTRUDA)","organisation_type":""}