Data from a phase 1 trial show that combined treatment with fianlimab plus cemiplimab exhibits high clinical activity and tolerable safety in advanced melanoma, consistent with other approved combinations of immune checkpoint inhibitors in this setting.

These findings were presented by lead author Omid Hamid, The Angeles Clinic & Research Institute, Los Angeles, California, at the 2023 American Society of Clinical Oncology (ASCO) Annual Meeting.

“Previous reports have demonstrated that treatment with anti-LAG-3 [antibody] fianlimab plus anti-PD-1 [antibody] cemiplimab had a 63.8% [objective response rate (ORR)] across 2 separate cohorts of advanced PD-(L)1 naïve metastatic melanoma patients,” wrote Dr Hamid and colleagues, adding “The benefit of the fianlimab plus cemiplimab combination in pts exposed to prior anti-PD-1 treatment as adjuvant treatment is unknown.”

Patients were enrolled in 3 separate expansion cohorts. Eligible patients had advanced unresectable or metastatic disease and were anti-PD-(L)1 treatment-naïve. Fianlimab was administered at 1600 mg cemiplimab at 350 mg intravenously once every 3 weeks for a duration of 12 months. Tumor measurements were performed every 6 weeks for a duration of 24 weeks, followed by additional assessments taking place every 9 weeks.

At the data cutoff date of November 1, 2022, 98 patients were enrolled and received treatment. Of the study population, 2% of patients had received prior metastatic treatment and 23.5% received prior systemic treatment in the adjuvant or neoadjuvant setting. Median follow up was 12.6 months and median treatment duration lasted 32.9 weeks.

Investigator-assessed overall objective response rate (ORR) was 61.2% with 12 complete responses and 48 partial responses. The median duration of response (DOR) was not reached (95% confidence interval [CI], 22.6 to not estimated). Median progression-free survival (PFS) by Kaplan Meier analysis was 15.3 months (95% CI, 9.4 to not estimated).

In patients who received prior adjuvant treatment (n = 23), the ORR was 60.9% (n = 14). Median DOR was not reached and median PFS was 13.3 months. In patients who received prior anti-PD-(L)1 adjuvant treatment (n = 13), ORR, median DOR, and median PFS were 61.5% (n = 8), not reached, and 11.8 months, respectively.

Grade ≥3 treatment-emergent adverse events (AEs) were reported in 43.9% of patients, serious treatment-emergent AEs were reported in 32.7% of patients, and immune-related AEs were reported in 65.3% of patients. Of those who experienced a treatment-emergent AE, 16.3% discontinued treatment due to symptom burden. The incidence of immune-related AEs was similar to that for those treated with PD-1 monotherapy but in this cohort adrenal insufficiency was prominent in 12.2% of patients.

“Fianlimab plus cemiplimab in advanced melanoma patients showed high clinical activity that compares favorably with other approved combinations of immune checkpoint inhibitors in the same clinical setting,” concluded Dr Hamid and colleagues, adding “This is the first indication [where a] dual LAG-3 blockade can produce high level of activity with significant ORR in [patients] with advanced [melanoma] post [adjuvant] anti-PD-1 [treatment].”

A phase 3 trial exploring this combination in treatment-naïve patients with advanced melanoma is currently ongoing.

Source:

Hamid O, Lewis KD, Weise AM, et al. Significant durable response with fianlimab (anti-LAG-3) and cemiplimab (anti-PD-1) in advanced melanoma: Post adjuvant PD-1 analysis. Presented at 2023 ASCO Annual Meeting; June 2-6, 2023; Chicago, IL. Abstract 9501