Dr Mehnert on the Efficacy of Sarilumab Plus Ipilimumab, Nivolumab, and Relatlimab in Unresectable Melanoma

“We were able to observe a best overall response rate of 63.6% and that's exciting, because it is one of the highest response rates we've seen in studies of immune checkpoint inhibition in melanoma to date.”

Janice M. Mehnert, MD, a professor in the Department of Medicine at NYU Grossman School of Medicine, director of the Melanoma Medical Oncology Program, and associate director of Clinical Research at Perlmutter Cancer Center, discussed the efficacy and safety profile of sarilumab (Kevzara) plus ipilimumab (Yervoy), nivolumab (Opdivo), and relatlimab for the treatment of patients with unresectable stage III or IV melanoma.

A phase 2 study (NCT05428007) evaluated the efficacy and safety of sarilumab added to ipilimumab, nivolumab, and relatlimab, findings of which were presented at the 2025 ASCO Annual Meeting. Of note, the 24-week overall response rate (ORR) was 63.6% (n = 21/33), Mehnert began. She noted that this finding was significant, as it was one of the highest response rates demonstrated compared with other studies assessing immune checkpoint inhibitors in patients with melanoma. Specifically, the ORR was 45.6% (n = 82/180) in the phase 3 Checkmate-511 trial (NCT02714218), and 58.7% (n = 27/46) in the phase 1/2 Relativity-048 trial (NCT03459222). At a median follow-up of 9.8 months, the 24-week clinical benefit rate was 78.8% (95% CI, 61.1%-91%) in the phase 2 study presented during the 2025 ASCO Annual Meeting.

Furthermore, there were no unexpected toxicities associated with the regimen, according to Mehnert. At week 24, grade 3/4 immune-related adverse effects (irAEs) occurred in 12.1% of patients, and any grade irAEs occurred in 93.9% of patients. Mehnert emphasized that the 24-week period was chosen for the coprimary end point of grade 3 to 5 irAEs because sarilumab was given for 24 weeks during the study. In a similar trend to ORR, she explained that the observed rate of grade 3/4 irAEs was lower than that observed in other studies that include anti–CTLA-4 in the regimen. Specifically, in Checkmate-511 and Relativity-048, the grade 3 to 5 irAEs occurred in 34% and 43% of patients, respectively.