Pilot Study of the Safety/Efficacy of Combination Checkpoint Blockade + External Beam Radiotherapy in Stage IV Melanoma

All subjects received concurrent ipilimumab (3 mg/kg) and nivolumab (1 mg/kg) every 3 weeks for 4 doses (i.e., Weeks 1, 4, 7 and 10), followed by nivolumab monotherapy administered at a dose of 240 mg every 2 weeks through Week 18. Continued nivolumab monotherapy was permitted beyond Week 18 at the Investigator's discretion as either 240 mg every 2 weeks or 480 mg every 4 weeks starting at Week 20. Extracranial RT was initiated after the first dose and before the second dose of immunotherapy, with RT dosing administered to a target lesion as follows: * Cohort A: conventional total palliative dose of 30 Gy delivered over 2 weeks in 10 fractions of 3 Gy each; * Cohort B: hypofractionated high-dose of 27 Gy delivered over 2 weeks in 3 fractions of 9 Gy each. Eligible subjects were initially enrolled into Cohort A. After 9 evaluable subjects completed at least the first 2 cycles of concurrent ipilimumab and nivolumab treatment, a safety review was performed and determined that the safety of Cohort A was acceptable based on a protocol-specified tolerability threshold of ≤ 7 of 9 subjects experiencing Grade 3 or 4 drug- or radiation-related adverse events (AEs), where Grade 3 or 4 amylase or lipase abnormalities that were not associated with clinical symptoms were not included in the safety assessment. Additional subjects were then accrued to Cohort B. Subjects were followed on study for 100 days after the last study drug administration. Post-study follow-up, which occurs at least every 12 (± 1) weeks for 3 years after completion of the 100-day on-study follow-up, is still being performed for some patients .