Poster Presentation Clinical Oncology Society of Australia Annual Scientific Meeting 2023

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 (#503)

Ana Baramidze 1 , Miranda Gogishvili 2 , Tamta Makharadze 3 , Mariam Zhvania 4 , Khatuna Vacharadze 5 , John Crown 6 , Tamar Melkadze 1 , Omid Hamid 7 , Georgina V. Long 8 , Caroline Robert 9 , Mario Sznol 10 , Héctor Martínez-Said 11 , Giuseppe Gullo 12 , Jayakumar Mani 12 , Usman Chaudhry 12 , Mark Salvati 12 , Israel Lowy 12 , Matthew G. Fury 12 , Karl D. Lewis 12
  1. Todua Clinic, Tbilisi, Georgia
  2. High Technology Medical Centre, University Clinic Ltd, Tbilisi, Georgia
  3. LTD High Technology Hospital Med Center, Batumi, Georgia
  4. Consilium Medulla, Tbilisi, Georgia
  5. LTD TIM Tbilisi Institute of Medicine, Tbilisi, Georgia
  6. St Vincent’s University Hospital, Dublin, Ireland
  7. The Angeles Clinical and Research Institute, a Cedars-Sinai Affiliate, Los Angeles, CA, USA
  8. Melanoma Institute Australia, The University of Sydney, and Royal North Shore and Mater Hospitals, Sydney, NSW, Australia
  9. Gustave Roussy and Paris Saclay University, Villejuif, France
  10. Yale Cancer Center, New Haven, CT, USA
  11. Melanoma Clinic, Instituto Nacional de Cancerología, Mexico City, Mexico
  12. Regeneron Pharmaceuticals, Inc., Tarrytown, NY, USA

 Fianlimab (anti-LAG-3) and cemiplimab (anti-PD-1) are high-affinity, fully human, IgG4 monoclonal antibodies. Concurrent blockade of anti-LAG-3 and anti-PD-1 has shown enhanced efficacy (increase in PFS) in advanced melanoma. Data from a Phase 1 study of fianlimab plus cemiplimab from three separate cohorts with advanced metastatic melanoma, two of which were PD-(L)1 naïve and a third with prior treatment in the (neo)adjuvant setting (72% had received prior anti-PD-(L)1), showed an aggregate ORR of 61% with an acceptable risk–benefit profile. These observations provide a rationale for using fianlimab plus cemiplimab in high-risk adjuvant melanoma (Phase 3 study, NCT05608291) and 1L metastatic melanoma (presented in this abstract).

 This is a randomized, double-blind, Phase 3 study to evaluate fianlimab plus cemiplimab compared with pembrolizumab in patients with previously untreated, unresectable locally advanced or metastatic melanoma (NCT05352672). This study will be conducted globally, at approximately 200 sites. Key inclusion criteria are: ≥12 years of age; histologically confirmed unresectable Stage III or Stage IV (metastatic) melanoma; no prior systemic therapy for advanced unresectable disease – prior (neo)adjuvant therapies are allowed with treatment/disease-free interval of 6 months; measurable disease per RECIST v1.1; valid LAG-3 results; ECOG PS of 0 or 1 (for adults), Karnofsky PS ≥70 (≥16 years) or Lansky PS ≥70 (<16 years); anticipated life expectancy ≥3 months.

The trial is expected to enroll approximately 1,590 patients, who will be randomized to Arms A, A1, B, or C and receive study treatment intravenously Q3W: A, cemiplimab + fianlimab dose 1; A1, cemiplimab + fianlimab dose 2; B, pembrolizumab + placebo; C, cemiplimab + placebo. The primary endpoint is PFS. Key secondary endpoints are OS and ORR. Additional secondary endpoints include DCR, DOR, safety, pharmacokinetics of cemiplimab and fianlimab, and immunogenicity (incidence and titer of anti-drug antibodies and neutralizing antibodies). The study is currently open for enrollment.