The combination of fianlimab and cemiplimab has demonstrated persistent and significant clinical activity in patients with advanced melanoma, according to data presented at the 2024 European Society of Medical Oncology (ESMO) Congress. The open-label, nonrandomized, multi-cohort expansion study (NCT03005782) showed a 57% overall response rate (ORR) by blinded independent central review (BICR) in a combined cohort of 98 patients, with a median follow-up of 23 months. This combination shows promise for melanoma patients, regardless of PD-L1 or LAG-3 status.
Efficacy Outcomes
The study, led by Dr. Meredith McKean from the Sarah Cannon Research Institute, evaluated the efficacy and safety of fianlimab plus cemiplimab in patients with advanced melanoma. The ORR of 57% included a complete response (CR) rate of 25% and a partial response (PR) rate of 33%. The disease control rate (DCR) was 78%. The median time to response was 1.5 months, and the median time to CR was 4.1 months. Notably, 70% of patients experienced some level of tumor reduction.
The median duration of response (DOR) was not reached (NR), and the median progression-free survival (PFS) was 24 months (95% CI, 12-NE). The 12- and 24-month PFS rates were 60% and 49%, respectively. The median overall survival was also not reached (95% CI, 42-NE).
Study Design and Patient Population
The study enrolled patients with metastatic or locally advanced, inoperable non-uveal melanoma across three cohorts. The initial cohort (MM1) included patients who had never received anti-PD-(L)1 therapy, while the confirmatory cohort (MM2) consisted of anti-PD-(L)1 naive patients with first-line advanced melanoma. The neoadjuvant/adjuvant experienced cohort (MM3) enrolled patients who had received prior perioperative systemic therapy, including some who had received anti-PD-(L)1 therapy.
All patients received fianlimab at 1600 mg combined with cemiplimab at 350 mg once every 3 weeks for up to 24 months. The primary endpoint was ORR per RECIST 1.1 criteria, with secondary endpoints including PFS, DOR, DCR, safety, and pharmacokinetics.
Subgroup Analysis
In patients with prior anti-PD-(L)1 treatment in the neoadjuvant or adjuvant setting (n = 13), the ORR was 46% with a CR rate of 31% and a DCR of 69%. In patients with liver metastases (n = 20), the ORR was 35% with a DCR of 55%. The subgroup with elevated lactate dehydrogenase (LDH) achieved an ORR of 55% with a DCR of 71%.
The ORRs were 50% and 71% in patients with PD-L1 expression of less than 1% and at least 1%, respectively. Similarly, the ORRs were 50% and 61% in patients with LAG-3 expression of less than 1% and at least 1%, respectively.
Safety Profile
The safety profile of the fianlimab plus cemiplimab combination was generally consistent with that of cemiplimab monotherapy. However, treatment-related adrenal insufficiency of any grade occurred in 12% of patients, with 5% experiencing grade 3 or higher effects. Interestingly, patients who experienced any-grade adrenal insufficiency (n = 12) had a high ORR of 92%.
Adverse events (AEs) of any grade occurred in 95% of patients, with grade 3 or higher AEs reported in 47% of patients. Serious AEs occurred in 36%, and immune-mediated AEs were noted in 13% of patients.
