Regeneron Pharmaceuticals, Inc. announced the presentation of positive data from multiple expansion cohorts of an initial Phase 1 trial for an investigational combination of LAG-3 inhibitor fianlimab and PD-1 inhibitor Libtayo® (cemiplimab) in advanced melanoma. The results were shared in a mini-oral session at the European Society for Medical Oncology (ESMO) Congress 2022 in Paris. Data presented at ESMO were from three dose expansion cohorts in advanced melanoma, including two that enrolled patients who had not previously been treated with a PD-1 or PD-L1 inhibitor (PD-1/PD-L1-naïve) and one of patients who had received prior PD-1 or PD-L1 inhibitor therapy (PD-1/PD-L1-experienced).

The objective response rate (ORR) in the PD-1/PD-L1-experienced cohort was 13%. Results from the PD-1/PD-L1-naïve cohorts were as follows: In updated results for one cohort (n=40), a 62.5% ORR (25 of 40 patients; 6 complete reponses [CR], 19 partial responses [PR]). Median duration of response (DOR) was not reached (range: 12 months to not evaluable [NE]) and the median progression-free survival (PFS) was 24 months (95% confidence interval [CI], 4 months to NE), per Kaplan-Meier estimates.

In a newly presented independent confirmatory cohort (n=40), a 65% ORR (26 of 40 patients; 1 CR, 25 PRs). The median DOR (range: 6 months to NE) and median PFS (95% CI, 7.5 to NE) were not reached, per Kaplan-Meier estimates. Tumor responses were based on RECIST 1.1 criteria and per investigator assessment.

AEs of any grade in the two PD-1/PD-L1-naïve cohorts (n= 80) occurred in 96% of patients, with 29% considered serious. The most common immune-mediated AEs in =15% patients were rash (n=19) and pruritus (n=12). AEs that were =grade 3 occurred in 40% of patients.

The treatment discontinuation rate due to AEs was 16%, with two deaths considered possibly related to treatment (colitis and cardiac shock). The potential use of fianlimab and Libtayo described above is investigational, and safety and efficacy of this combination have not been evaluated by any regulatory authority.