Early Clinical Data for Combination of Fianlimab, Cemiplimab Shows Clinically Meaningful Results in Advanced Melanoma

Regeneron Pharmaceuticals Inc has announced positive data from 3 independent cohorts evaluating an investigational combination of fianlimab, a LAG-3 inhibitor, and cemiplimab (Libtayo), a PD-1 inhibitor, in adults with advanced melanoma.

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The early clinical data demonstrated that the combination had clinically meaningful and durable results in various clinical settings. The results will be shared in an oral session at the 2023 American Society of Clinical Oncology Annual Meeting (ASCO) in Chicago.

“LAG-3 inhibitors are known to complement PD-1 inhibitors in the treatment of advanced melanoma. There exists an unmet need to further improve the benefit to patients, including those with liver metastases and other high-risk prognostic markers,” Omid Hamid, MD, director of Clinical Research and Immunotherapy at The Angeles Clinic and Research Institute, said in a statement. “These updated and independent expansion cohort results reinforce the potential of the fianlimab and cemiplimab combination to deliver clinically meaningful and durable responses in diverse clinical settings and patient populations, with an acceptable safety profile. Particularly encouraging is that the clinical activity was observed in post hoc analyses of patient subgroups, including in patients with a poor prognosis or those who had been previously treated with an anti-PD-1 therapy in the adjuvant setting.”

The 3 cohorts included adults with unresectable or metastatic melanoma who were all naïve to anti-PD-1 therapy for advanced disease. Tumor responses were based on the RECIST 1.1 criteria and investigator assessment.

Investigators reported that the median duration of response was not reached in any of the 3 cohorts. In the initial cohort, 63% of patients achieved an objective response rate (ORR), including 6 who had a complete response (CR) and 19 who had a partial response (PR).

In the confirmatory cohort, 63% of individuals achieved an ORR, including 5 CRs and 20 PRs. Among those in the prior neo/adjuvant systemic therapy cohort, 56% achieved an ORR, with 13 patients in the attest cohort who had prior anti-PD-1 adjuvant treatment achieving an ORR of 62%, with 1 CR and 7 PRs.

The post hoc analysis of the 3 combined cohorts showed an ORR of 61%, with a median progression-free survival of 15 months per Kaplan-Meier estimate, and the median follow up was 13 months, ranging from 9 to 19.

In multiple subgroups, investigators found clinically meaningful activity, with an ORR of 53% for individuals with high baseline lactate dehydrogenase (LDH), of whom 43% had liver metastasis and 35% had M1c stage disease and high baseline of LDH.

Additionally, investigators found that there was an ORR of 73% for those who had 1% PD-L1 expression or greater and 56% for those who had less than 1% PD-L1 expression.

Investigators also reported that the safety profile of the combination was generally consistent with the safety profile of cemiplimab and other anti-PD-L1 agents, except for a higher rate of adrenal insufficiency, which were grade 2 or less in the majority of cases. All cases were successfully managed with steroid replacement.

Adverse events (AEs) were observed in 94% of individuals, with 44% being grade 3 or greater and 30% considered serious. AEs included rash, pruritis, diarrhea, arthralgia, hypothyroidism, adrenal insufficiency, and myalgia. The discontinuation rate due to AEs was 16%.

Additional follow up will be reported on an initial cohort in the first- and second-line treatment groups and a confirmatory cohort of patients receiving first-line treatment, which was previously reported at the European Society for Medical Oncology.

Furthermore, additional presentations on the combination will be shared at ASCO during a poster session, including:

• A phase 1 study of fianlimab (anti-LAG-3) in combination with cemiplimab (anti-PD-1) in patients with advanced melanoma: poor prognosis subgroup analysis (#9548).
• A phase 3 trial of fianlimab (anti-LAG-3) plus cemiplimab (anti-PD-1) versus pembrolizumab in patients with previously untreated unresectable locally advanced or metastatic melanoma (#TPS9602).
• A phase 3 trial comparing fianlimab (anti-LAG-3) plus cemiplimab (anti-PD-1) to pembrolizumab in patients with completely resected high-risk melanoma (#TPS9598).

Reference

Fianlimab (LAG-3 inhibitor) combined with Libtayo (cemiplimab) shows clinically meaningful and durable tumor responses across key advanced melanoma patient populations. News release. Regeneron. May 25, 2023. Accessed May 30, 2023. https://investor.regeneron.com/news-releases/news-release-details/fianlimab-lag-3-inhibitor-combined-libtayor-cemiplimab-shows