Dr Postow on the Potential Role for Triplet Regimens in Melanoma

"Both of de novo metastatic and PD-1 inhibitor–refractory metastatic [melanoma] could be opportunities [to use] triplet [regimens]. It remains to be seen how effective [triplet regimens] can be, but we hope it will really help patients who are not currently served by doublets."

Michael A. Postow, MD, chief, Melanoma Service, co-Director, Melanoma Disease Management Team, Memorial Sloan Kettering Cancer Center, discusses the potential role for triplet regimens in melanoma managemnet.

Triplet regimens represent a new frontier in the treatment of patients with advanced melanoma, Postow begins. Preliminary data from the phase 1/2 RELATIVITY-048 trial (NCT03459222), which were presented at the 2024 ASCO Annual Meeting, demonstrated high response rates and durable outcomes with the addition of ipilimumab (Yervoy) to nivolumab and relatlimab-rmbw (Opdualag) as first-line therapy. At a median follow-up of 49.4 months, the triplet combination achieved an overall response rate (ORR) of 59% by investigator assessment and 52% by blinded independent central review (BICR). Notably, median progression-free survival (PFS), overall survival (OS), and duration of response (DOR) were not reached. The 48-month PFS and OS rates were 52% and 72%, respectively.

A unique feature of this triplet regimen is the adjusted dosing of ipilimumab, which is administered at a lower dose and less frequently, Postow explains, adding that this could enhance tolerability. Despite these results, randomized data for triplets remain unavailable, and the therapy is not yet approved, Postow states.

Triplet regimens are also being investigated in the context of PD-1 inhibitor–refractory melanoma, he continues. This is particularly relevant for patients who progress after treatment with a PD-1 inhibitor in the neoadjuvant or adjuvant setting, Postow notes. Clinical trials are underway to determine whether triplets offer superior efficacy compared with standard doublet regimens in this patient population.

Both de novo metastatic melanoma and PD-1 inhibitor–refractory disease represent critical opportunities for triplet therapy, Postow emphasizes. Although further research is needed to establish efficacy and optimize sequencing, these regimens could provide meaningful options for patients underserved by current doublet approaches, he concludes.