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 

 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.

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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 

Dr Mehmi on the Rationale for Investigating Fianlimab/Cemiplimab in Advanced Melanoma

Inderjit Mehmi, MD, medical oncologist, The Angeles Clinic and Research Institute, discusses updated results from a subgroup analysis of patients with advanced melanoma and poor-risk features who were treated with fianlimab (REGN3767) and cemiplimab (Libtayo) in a phase 1 trial (NCT03005782).

The open-label, non-randomized, parallel-cohort assignment study enrolled patients with unresectable or metastatic melanoma to 1 of 3 expansion cohorts: the initial cohort, a confirmatory cohort, and a PD-L1--experienced cohort. Those in the first 2 expansion cohorts had not been previously exposed to anti-PD-1 therapy, while those in cohort 16 had been previously exposed to adjuvant or neoadjuvant systemic therapy, including a PD-L1 inhibitor.

Data from the PD-L1 inhibitor–naïve cohorts were previously reported in July 2022 and demonstrated efficacy with the LAG-3 and PD-1 inhibitor combination. In the current analysis, responses to the regimen were evaluated in patients with poor prognosis melanoma across all 3 cohorts. It included patients with liver metastasis (n = 21), high baseline lactate dehydrogenase (LDH) levels (n = 32), and M1c stage disease plus LDH greater than the upper limit of normal (ULN) at baseline (n = 17).

Findings from this analysis were presented at the 2023 ASCO Annual Meeting.

Across all 3 expansion cohorts, patients without liver metastasis at baseline experienced an overall response rate (ORR) of 66%, a disease control rate (DCR) of 83%, a median progression-free survival (PFS) of 24 months, and the median duration of response (DOR) was not reached with the experimental regimen. Conversely, those with liver metastasis had an ORR of 43%, DOR of 57%, median PFS of 4 months, and median DOR of 9 months. Similarly, those with a normal LDH baseline had an ORR of 66%, DCR of 81%, median DOR of 23 months and median PFS of 27 months. Corresponding measures were 53%, 72%, not reached, and 12 months, respectively, in those with high LDH levels. Lastly, patients without M1c stage disease but with high baseline LDH had an ORR of 45%, DCR of 55%, median DOR not reached, and median PFS of 6 months. Patients with M1c stage disease and high LDH had an ORR of 35%, median PFS of 7 months, DCR of 59% and median DOR that was not reached.

Overall, fianlimab and cemiplimab produced clinically meaningful activity in all poor-risk subgroups despite these groups experiencing decreased responses vs lower-risk patients. Accordingly, Mehmi states that these data are still encouraging for patients thought to do poorly on immune checkpoint inhibitors due to their disease status, elevated LDH, and overall disease burden.

Inderjit Mehmi, MD, discusses results from a subgroup analysis of patients with advanced melanoma and poor-risk features given fianlimab and cemiplimab in a phase 1 trial.



Inderjit Mehmi, MD

Articles

Dr Mehmi on the Rationale for Investigating Fianlimab/Cemiplimab in Advanced Melanoma

Dr. Mehmi on Fianlimab and Cemiplimab in Patients with Poor-Risk, Advanced Melanoma