On May 25, 2023 Regeneron Pharmaceuticals, Inc. (NASDAQ: REGN) reported positive data from three independent cohorts evaluating an investigational combination of LAG-3 inhibitor fianlimab and PD-1 inhibitor Libtayo (cemiplimab) in adults with advanced melanoma (Press release, Regeneron, MAY 25, 2023, View Source [SID1234632071]). The early clinical trial results, which demonstrated the combination led to clinically meaningful and durable results across multiple clinical settings, will be shared in an oral session at the 2023 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting in Chicago on Monday, June 5 at 3:00 PM CT.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"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," said Omid Hamid, M.D., Director, Clinical Research and Immunotherapy at The Angeles Clinic and Research Institute, and principal investigator of the trial. "These updated and independent expansion cohort results reinforce the potential of the fianlimab and cemiplimab (Libtayo) 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 data to be presented at ASCO (Free ASCO Whitepaper) 2023 include findings from three independent expansion cohorts of adults with unresectable or metastatic melanoma who were all naïve to anti-PD-1 therapy for advanced disease (n=98). Additional follow up will be reported on an initial cohort of first- or second-line patients (n=40) and a confirmatory cohort of first-line patients (n=40), previously reported at ESMO (Free ESMO Whitepaper) 2022. New for this presentation is a cohort of patients who had received prior systemic treatment for melanoma in the neoadjuvant or adjuvant setting (n=18), including adjuvant anti-PD-1 therapy (n=13 of 18).

Tumor responses were based on RECIST 1.1 criteria and per investigator assessment. The median duration of response (DOR) was not reached in any cohort, and the objective response rate (ORR) by cohort was as follows:

Initial cohort: 63% (25 of 40 patients), including 6 complete responses (CR) and 19 partial responses (PR).
Confirmatory cohort: 63% (25 of 40 patients), including 5 CRs and 20 PRs.
Prior neo/adjuvant systemic therapy cohort: 56% (10 of 18 patients). Among the 13 patients in this latest cohort who had prior anti-PD-1 adjuvant treatment, the ORR was 62% (8 of 13 patients), including 1 CR and 7 PRs.
In a post hoc analysis of the three combined cohorts, the ORR was 61% (60 of 98 patients), the median progression-free survival (PFS) was 15 months per Kaplan-Meier estimate (95% CI: 9–NE), and the median follow-up was 13 months (interquartile range 9-19). Additional post hoc analyses found clinically meaningful activity in multiple subgroups of interest, with ORRs in each as follows:

Poor prognosis: 53% (17 of 32 patients) in cases with high baseline lactate dehydrogenase (LDH), 43% (9 of 21 patients) in cases of liver metastasis, and 35% (6 of 17 patients) in cases of M1c stage (visceral metastatic) disease and high baseline LDH.
Varying tumor PD-L1 expression levels: 73% (19 of 26 patients) in cases of ≥1% PD-L1 expression and 56% (23 of 41 patients) in cases of <1% PD-L1 expression.
The safety profile of the fianlimab and Libtayo combination in these expansion cohorts appeared to be generally consistent with the safety profile of Libtayo monotherapy and other anti-PD-(L)1 agents, except for higher rates of adrenal insufficiency, which were ≤Grade 2 in the majority of cases (64%) and all cases were successfully managed with steroid replacement. Adverse events (AEs) occurred in 94% of patients, with 44% being ≥Grade 3 and 30% considered serious. AEs occurring in ≥10% of patients included rash (20%), pruritis (16%), diarrhea (15%), arthralgia (13%), hypothyroidism (12%), adrenal insufficiency (11%) and myalgia (10%). The treatment discontinuation rate due to AEs was 16%.

"Fianlimab in combination with Libtayo has now demonstrated robust response rates in three independent advanced melanoma cohorts – each with unique patient populations," said Israel Lowy, M.D., Ph.D., Senior Vice President, Translational and Clinical Sciences, Oncology at Regeneron. "These positive results support the clinical potential of fianlimab in combination with Libtayo. We look forward to partnering with the oncology community to further investigate this combination in a broad pivotal clinical development program that includes Phase 3 trials in the advanced and adjuvant melanoma settings, alongside ongoing Phase 2/3 trials in non-small cell lung cancer and research in other solid tumors."

Additional presentations on the fianlimab and Libtayo combination will be shared at ASCO (Free ASCO Whitepaper) during a poster session on Saturday, June 3 from 1:15 to 4:15 PM CT, 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)
The potential use of fianlimab and Libtayo described above is investigational, and safety and efficacy of this combination have not been evaluated by any regulatory authority.