Triple Immune Checkpoint Inhibition for Advanced or Metastatic PD-(L)1 Refractory Merkel Cell Carcinoma

OUTLINE: All patients receive the same investigational drug combination. SCREENING: Patients undergo history and physical examination, adverse event assessment, safety and eligibility labs, radiologic evaluation with computed tomography (CT)/magnetic resonance imaging (MRI), and complete informed consent. INDUCTION PHASE: Patients receive anti-LAG-3 and anti-TIM-3 intravenously (IV) every 2 weeks along with retifanlimab (anti-PD-1) IV every 4 weeks, along with clinical visit, physical examination, and labs for safety. Treatment continues for up to day 169 in the absence of disease progression or unacceptable toxicity. Patients undergo CT/MRI every 8 weeks. Research tumor biopsies will be obtained on day 1 and day 15 unless unsafe and unfeasible. Research blood draws will occur at day 1, day 15, and periodically throughout Induction Phase. MAINTENANCE PHASE: Patients receive all three drugs IV every 6 weeks along with clinical visit, physical examination, and labs for safety. Treatment continues for up to day 715 in the absence of disease progression or unacceptable toxicity. Patients undergo CT/MRI every 12 weeks. Research blood sample collection will continue periodically. Patients with progressive disease per investigator evaluation will stop receiving therapy. Research blood and tumor biopsies will be obtained at time of progression if safe and feasible. Upon completion of study treatment (day 715 or sooner for disease progression), safety visits occur at 30 and 90 days. Follow up for long term outcomes continues every 6 months for up to 5 years.