Regeneron Pharmaceuticals' investigational combination therapy of fianlimab and Libtayo continues to show promising results in patients with advanced melanoma, with benefits sustained beyond two years. The longer-term data, presented at the European Society for Medical Oncology (ESMO) Annual Meeting, highlight the potential of this combination as a treatment option for this aggressive skin cancer.
The Phase I trial (NCT03005782) involved 98 adult patients with advanced melanoma, divided into three cohorts: an initial cohort, a confirmatory cohort, and a neo/adjuvant experienced cohort. Patients received treatment for 12 months, with the study evaluating the combination of fianlimab, a LAG-3 inhibitor, and Libtayo (cemiplimab), an anti-PD-L1 antibody.
Durable Responses Observed
After a median follow-up of 23 months, the combined cohorts showed a 25% complete response (CR) rate and a 57% objective response rate (ORR). Specifically, the initial cohort had a 23% CR rate and a 60% ORR, while the confirmatory cohort demonstrated a 25% CR rate and a 63% ORR. The cohort with prior neoadjuvant or adjuvant systemic therapy achieved a 28% CR rate and a 39% ORR.
The median time to response was 1.5 months, and the median time to complete response was 4.1 months. The median duration of response was not reached, indicating a sustained treatment effect. The overall median progression-free survival (PFS) was 24 months.
Safety Profile
The safety profile of the combination therapy was consistent with that of Libtayo monotherapy and other anti-PD-L1 agents, with the exception of higher rates of treatment-related adrenal insufficiency. This is an important consideration for clinicians when managing patients on this regimen.
Expert Commentary
Dr. Meredith McKean, director of the Melanoma and Skin Cancer Research Program at Sarah Cannon Research Institute, noted the excitement surrounding the doubling of the objective response rate with fianlimab and Libtayo compared to anti-PD-1 monotherapies. She highlighted an ongoing, randomized Phase III trial in frontline metastatic melanoma, with results expected in 2025.
Ongoing Phase III Trials
Regeneron is currently conducting four Phase III studies of the combination therapy. One trial (NCT05352672) compares the combination to Keytruda (pembrolizumab) in previously untreated unresectable locally advanced or metastatic melanoma. Additional trials are evaluating the combination in the adjuvant (NCT05608291) and perioperative settings (NCT06190951), as well as against other first-line, standard-of-care LAG3 and PD-1 combinations (NCT06246916).
