Dr. Jeffrey S. Weber on Why the Results of CheckMate-064 Were Surprising

Jeffrey S. Weber, MD, PhD, deputy director and co-director of the Melanoma Program, Laura and Isaac Perlmutter Cancer Center at NYU Langone Medical Center, discusses the findings of the phase II CheckMate-064 trial and the role of sequential versus concurrent Immunotherapy in melanoma.

Patients in the trial were randomized to receive either nivolumab followed by ipilimumab followed by nivolumab maintenance therapy, or ipilimumab followed by nivolumab and maintenance therapy with nivolumab. The trial was conducted to try and achieve equal efficacy of concurrent therapy by sequencing the drugs to lower the toxicity.

Looking beyond week 25 to include maintenance therapy, about half of patients received maintenance treatment in either arm. There was well over a 50% rate of grade 3/4 adverse events in arm A and a slightly lower rate in arm B. This suggests that, in terms of toxicity, sequential therapy did not do better than concurrent therapy, said Weber.

However, the response rates between the two arms were surprising. Arm A had a best overall response rate (ORR) of about 54%, while Arm B had a 30% ORR. This translated into a very impressive difference in survival, said Weber.

These results imply that getting the induction of ipilimumab with the forced switch to nivolumab could have compromised patients’ ability to respond to the subsequent nivolumab, he said.