A phase 2 clinical trial on neoadjuvant pembrolizumab in patients diagnosed with high-risk melanoma without clinical evidence of metastatic dissemination.

Prior treatment

• Prior transplantation of human cells, tissues and organs (e.g. liver transplant) or candidates for any type of transplantation.
• Patients who have previously been exposed to checkpoint inhibitors

Other illness

• Known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
• Active autoimmune disease requiring systemic treatment
• 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.
• 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.
• Active infection at the time of screening (e.g. wound infection)
• Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to the study treatment, or excipients
• History of organ allograft.

Lab values

• 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.
• 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.

Other

• Patients with uveal melanoma and melanoma of unknown primary origin.
• Any contra-indication for evaluation by whole body 18F-FDG-PET/CT or MRI.

• ≥18 years of age on the day of signing informed consent.
• 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
• Histologically confirmed high risk primary cutaneous pT1b-4b melanoma. High risk primary melanoma is defined in this study as the following AJCC8 T-stages: • pT1b-3a, with a poor prognostic score on the Merlin™ test (“Merlin™ high risk”); • pT3b-4b, irrespective of their Merlin™ test result
• Amenable to sentinel lymph node biopsy.
• No evidence of metastatic dissemination as demonstrated by PET/CT, ultrasound of the draining lymph node basin, and clinical examination.
• No prior exposure to systemic treatment for melanoma.
• 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.
• 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.
• Women: a. Not a woman of childbearing potential (WOCBP) b. Women 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. Women who are not breastfeeding
• 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.