Study: Fianlimab With Cemiplimab Combination Shows High Response Rate in Certain Patients With Advanced Melanoma

An investigational combination of fianlimab, a LAG-3 inhibitor, and cemiplimab (Libtayo; Regeneron Pharmaceuticals, Inc), a PD-1 inhibitor, showed positive data in a phase 1 trial among patients with advanced melanoma. The results were presented at the European Society for Medical Oncology Congress 2022.

The objective response rate (ORR) was high in more than half of participants administered the combination of fianlimab and cemiplimab and who were not previously treated with a programmed cell death protein 1 (PD-1) or programmed death-ligand 1 (PD-L1) inhibitor.

“In 2 independent dose expansion cohorts from a phase 1 clinical trial of patients naïve to PD-1 or PD-L1 inhibitors, our LAG-3 inhibitor fianlimab combined with Libtayo demonstrated greater than 60% response rates,” said Israel Lowy, MD, PhD, senior vice president, Translational and Clinical Sciences, Oncology at Regeneron, in a press release. 

Researchers examined 3 different cohorts of patients with advanced melanoma, 2 of which were independent groups of enrolled patients were never treated with a PD-1 or PD-L1 inhibitor. The other group enrolled patients who had been treated with PD-1 or PD-L1 inhibitor therapy.

Among one of the independent groups who was not previously treated with a PD-1 or PD-L1 inhibitor (PD-1/PD-L1-naïve), the median progression-free survival (PFS) averaged 24 months, with an ORR of 62.5%. The other naïve cohort experienced a 65% ORR, however there was not a median PFS.

The ORR of the cohort previously treated with PD-1 or PD-L1 inhibitor therapy was 13%. The research suggests that the combination led to high response rates in both independent PD-1/PD-L1-naïve groups, according to the study authors. However, “achieving response rates above 50% has been challenging” for patients who were already treated with a PD-1 inhibitor, Lowy said in the press release.

The most common adverse events (AEs) caused by the immune system were rash and pruritus, occurring in 19 patients. Among the entire patient population, 40% experienced AEs that were grade 3 or higher.

Fianlimab is a fully human monoclonal antibody that targets LAG-3, an immune checkpoint receptor on T cells. LAG-3 expresses on cancer cells in melanoma and is also associated with resistance to PD-1 inhibitors.

Cemiplimab is also a fully human monoclonal antibody that targets and binds to PD-1, an immune checkpoint receptor. Upon binding to this receptor, cemiplimab can stop cancer cells from travelling through the PD-1 pathway and suppressing T cells.

The safety profile of fianlimab and cemiplimab was found to be similar to cemiplimab as a monotherapy, however the combination was not evaluated by a regulatory authority.

“A phase 3 trial in first-line metastatic melanoma is currently enrolling patients, and we look forward to opening additional trials with this combination in the near future," Lowy concluded in the press release.

Reference

Regeneron. FIANLIMAB (LAG-3 INHIBITOR) COMBINED WITH LIBTAYO® (CEMIPLIMAB) DEMONSTRATES GREATER THAN 60% RESPONSE RATES IN TWO INDEPENDENT COHORTS OF PATIENTS WITH ADVANCED MELANOMA NAÏVE TO PD-1 OR PD-L1 INHIBITORS. Regeneron website. September 12, 2022. Accessed on September 13, 2022. https://investor.regeneron.com/news-releases/news-release-details/fianlimab-lag-3-inhibitor-combined-libtayor-cemiplimab