A Study Evaluating Whether Pembrolizumab Alone or in Combination With CMP-001 Improves Efficacy of Treatment in Patients With Operable Melanoma

PRIMARY OBJECTIVE: I. To evaluate the rate of pathologic complete response (pCR) rate in patients in each arm. SECONDARY OBJECTIVES: I. To evaluate the rate of pathologic near-complete/major response (pMR) of the neoadjuvant therapy in each arm. II. To evaluate the pathologic response rate of un-injected lesions on the combination arm (Arm B). III. To evaluate relapse-free survival (RFS) in each arm. IV. To evaluate overall survival (OS) in each arm. V. To evaluate the preoperative radiographic response rate in each arm. VI. To evaluate safety and toxicity of neoadjuvant therapy in each arm. OUTLINE: Patients are randomized to 1 of 2 arms. ARM A: NEOADJUVANT PHASE: Patients receive pembrolizumab intravenously (IV) over 30 minutes on day 1 of each cycle. Treatment repeats every 21 days for up to 3 cycles in the absence of disease progression or unacceptable toxicity. SURGERY: Patients undergo surgery 1-2 weeks after completion of neoadjuvant phase. ADJUVANT PHASE: After recovery from surgery, patients receive pembrolizumab IV over 30 minutes on day 1 of every other cycle. Treatment repeats every 21 days for up to 16 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo computed tomography (CT) or positron emission tomography (PET)/CT throughout the trial and may undergo optional biopsy at baseline and disease progression and optional collection of blood samples throughout the trial. ARM B: NEOADJUVANT PHASE: Patients receive VLP-encapsulated TLR9 agonist CMP-001 (CMP-001) subcutaneously (SC) on day 1 of cycle 1 and then intratumorally on days 8 and 15 of cycle 1, days 1, 8, and 15 of cycle 2, and day 1 of cycle 3. Patients also receive pembrolizumab IV over 30 minutes on day 8 of each cycle. Treatment repeats every 21 days for up to 3 cycles in the absence of disease progression or unacceptable toxicity. SURGERY: Patients undergo surgery 1-2 weeks after completion of neoadjuvant phase. ADJUVANT PHASE: After recovery from surgery, patients receive pembrolizumab IV over 30 minutes on day 1 of every other cycle. Treatment repeats every 21 days for up to 16 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo CT or PET/CT throughout the trial and may undergo optional biopsy at baseline and disease progression and optional collection of blood samples throughout the trial. After completion of study treatment, patients are followed up at 30 days and then every 3 months if \< 2 years from study entry, every 6 months if 2-5 years from study entry, and every 12 months if \> 5 years from study entry for up to 10 years (15 years total follow up).