Dr. Mehmi on Fianlimab and Cemiplimab in Patients with Poor-Risk, Advanced Melanoma

Inderjit Mehmi, MD, medical oncologist, The Angeles Clinic and Research Institute, discusses updated results from a subgroup analysis of patients with advanced melanoma and poor-risk features who were treated with fianlimab (REGN3767) and cemiplimab (Libtayo) in a phase 1 trial (NCT03005782).

The open-label, non-randomized, parallel-cohort assignment study enrolled patients with unresectable or metastatic melanoma to 1 of 3 expansion cohorts: the initial cohort, a confirmatory cohort, and a PD-L1--experienced cohort. Those in the first 2 expansion cohorts had not been previously exposed to anti-PD-1 therapy, while those in cohort 16 had been previously exposed to adjuvant or neoadjuvant systemic therapy, including a PD-L1 inhibitor.

Data from the PD-L1 inhibitor–naïve cohorts were previously reported in July 2022 and demonstrated efficacy with the LAG-3 and PD-1 inhibitor combination. In the current analysis, responses to the regimen were evaluated in patients with poor prognosis melanoma across all 3 cohorts. It included patients with liver metastasis (n = 21), high baseline lactate dehydrogenase (LDH) levels (n = 32), and M1c stage disease plus LDH greater than the upper limit of normal (ULN) at baseline (n = 17).

Findings from this analysis were presented at the 2023 ASCO Annual Meeting.

Across all 3 expansion cohorts, patients without liver metastasis at baseline experienced an overall response rate (ORR) of 66%, a disease control rate (DCR) of 83%, a median progression-free survival (PFS) of 24 months, and the median duration of response (DOR) was not reached with the experimental regimen. Conversely, those with liver metastasis had an ORR of 43%, DOR of 57%, median PFS of 4 months, and median DOR of 9 months. Similarly, those with a normal LDH baseline had an ORR of 66%, DCR of 81%, median DOR of 23 months and median PFS of 27 months. Corresponding measures were 53%, 72%, not reached, and 12 months, respectively, in those with high LDH levels. Lastly, patients without M1c stage disease but with high baseline LDH had an ORR of 45%, DCR of 55%, median DOR not reached, and median PFS of 6 months. Patients with M1c stage disease and high LDH had an ORR of 35%, median PFS of 7 months, DCR of 59% and median DOR that was not reached.

Overall, fianlimab and cemiplimab produced clinically meaningful activity in all poor-risk subgroups despite these groups experiencing decreased responses vs lower-risk patients. Accordingly, Mehmi states that these data are still encouraging for patients thought to do poorly on immune checkpoint inhibitors due to their disease status, elevated LDH, and overall disease burden.