Inderjit Mehmi, MD, medical oncologist, discusses the rationale for investigating the combination of fianlimab and cemiplimab in patients who have advanced melanoma with poor-risk features
Inderjit Mehmi, MD, medical oncologist, Cedars-Sinai The Angeles Clinic and Research Institute, discusses the rationale for investigating the combination of fianlimab (REGN3767) and cemiplimab (Libtayo) in patients who have advanced melanoma with poor-risk features.
At the 2023 ASCO Annual Meeting, investigators presented updated results from an exploratory subgroup analysis of an open label, non-randomized, phase 1 clinical trial (NCT03005782) examining the combination. Investigators found that fianlimab and cemiplimab produced clinical activity in patients with advanced melanoma who have characteristics associated with poor prognosis. These characteristics include the presence of liver metastases, elevated LDH grade, and M1c stage disease.
Moreover, the combination of fianlimab and cemiplimab was found to have a safety profile consistent with that of single-agent cemiplimab, as well as other PD-1/PD-L1 treatment options. However, a higher grade of adrenal insufficiency was noted with the use of this doublet.
This combination is now being brought into the treatment landscape for unresectable metastatic melanoma amid the continued investigation of various immune checkpoint inhibitors in this tumor type, Mehmi says. Notably, checkpoint inhibitors have been shown to improved overall survival in this patient population. Fianlimab and cemiplimab are novel immune checkpoint inhibitors in this space, he explains. Fianlimab works by blocking LAG3 interaction, which allows immune cells to be redirected towards the melanoma; cemiplimab is a PD-1 blocker. PD-1 blockers are known to have beneficial responses in melanoma, Mehmi expands. However, better responses are desired for this patient population, leading to the investigation of fianlimab alongside cemiplimab.
When Combining LAG3 and PD-1 inhibition, it was hypothesized to improve response rates for these patients, Mehmi notes. Such improvements have been demonstrated in previous clinical research, such the phase 3 RELATIVITY-047 study (NCT03470922). Results from this trial ultimately led to the FDA approval of relatlimab-rmbw (Opdualag) with nivolumab (Opdivo) in the treatment of patients with unresectable or metastatic melanoma.
Fianlimab and cemiplimab represents a similar approach, and may provide another effective option for patients with unresectable melanoma, Mehmi concludes.