Anti–LAG-3/PD-1 Combination Under Investigation as Adjuvant Therapy in High-Risk Melanoma

Source: OncLive, June 2023

The combination of fianlimab and cemiplimab-rwlc (Libtayo) represents a wave of novel anti–LAG-3/PD-1 treatments being explored in patients with melanoma at high risk for relapse, according to the rationale and design of an ongoing phase 3 trial (NCT05608291) that were presented at the 2023 ASCO Annual Meeting.

“The longer relapse-free survival [RFS] and lower toxicity has made PD-1 inhibitors the standard of care as adjuvant therapy in patients with high-risk melanoma,” Timothy J. Panella, MD, of the University of Tennessee Medical Center at Knoxville, said during a presentation of the trial in progress. “Despite these recent advances, a significant portion of patients will relapse. Hence, for patients with resectable high-risk melanoma, there is a high need for a treatment that is more efficacious than anti–PD-1 monotherapy with good tolerability.”

The immune checkpoint receptor LAG-3 is a potentially relevant therapeutic target in melanoma because it suppresses cytokine secretion and T-cell activation. Previously, in the phase 2/3 RELATIVITY-047 trial (NCT03470922), the fixed-dose combination of the LAG-3 inhibitor relatlimab-rmbw plus the PD-1 inhibitor nivolumab (Opdualag) produced a median progression-free survival (PFS) of 10.1 months compared with 4.6 months with nivolumab alone in patients with treatment-naïve metastatic or unresectable melanoma,2 leading to the 2022 FDA approval of the combination in this population.