Poster Presentation Clinical Oncology Society of Australia Annual Scientific Meeting 2023

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 (#224)

Inderjit Mehmi 1 , Amy Weise 2 , Meredith McKean 3 , Kyriakos P. Papadopoulos 4 , John Crown 5 , Sajeve S. Thomas 6 , Janice Mehnert 7 , John Kaczmar 8 , Kevin B. Kim 9 , Nehal J. Lakhani 10 , Melinda Yushak 11 , Omid Hamid 1 , Tae Min Kim 12 , Guilherme Rabinowits 13 , Alexander Spira 14 , Giuseppe Gullo 15 , Jayakumar Mani 15 , Fang Fang 15 , Shuquan Chen 15 , JuAn Wang 15 , Israel Lowy 15 , Mark Salvati 15 , Matthew G. Fury 15 , Karl D. Lewis 15
  1. The Angeles Clinical and Research Institute, a Cedars-Sinai Affiliate, Los Angeles, CA, USA
  2. Henry Ford Hospital, Detroit, MI, USA
  3. Sarah Cannon Research Institute/Tennessee Oncology PLLC, Nashville, TN, USA
  4. START Center, San Antonio, TX, USA
  5. St Vincent’s University Hospital, Dublin, Ireland
  6. University of Florida Health Cancer Center at Orlando Health, Orlando, FL, USA
  7. Rutgers Cancer Institute of New Jersey, New Brunswick, NJ, USA
  8. MUSC Hollings Cancer Center, North Charleston, SC, USA
  9. Center for Melanoma Research and Treatment, California Pacific Medical Center Research Institute, San Francisco, CA, USA
  10. START Midwest, Grand Rapids, MI, USA
  11. Department of Hematology and Medical Oncology at Emory University School of Medicine, Atlanta, GA, USA
  12. Seoul National University Hospital, Seoul, South Korea
  13. Department of Hematology and Oncology, Miami Cancer Institute/Baptist Health South Florida, Miami, FL, USA
  14. Virginia Cancer Specialists and US Oncology Research, Fairfax, VA, USA
  15. Regeneron Pharmaceuticals, Inc., Tarrytown, NY, USA

Aims: Co-blockade of LAG-3 improves the effectiveness of anti-PD-1 treatment in advanced melanoma patients. We present updated efficacy data for poor prognosis patients from three Phase 1 expansion cohorts with advanced melanoma: anti-PD-(L)1/systemic treatment-naïve (cohorts 6 and 15); previously exposed to adjuvant/neoadjuvant systemic treatment, including anti-PD-1 (cohort 16).

Methods: Patients with advanced melanoma were treated with fianlimab 1600 mg plus cemiplimab 350 mg intravenously Q3W for 12 months, with a further 12 months if clinically indicated (NCT03005782). Tumor measurements were assessed by RECIST 1.1 every 6 weeks for 24 weeks, then every 9 weeks.

Results: 40 patients each in cohorts 6 and 15, and 18 patients in cohort 16, were enrolled and treated (N=98; Nov 1, 2022 data cutoff). In the adjuvant/neoadjuvant setting, 24% of patients had received prior systemic treatment for melanoma, including 15% with prior exposure to immune checkpoint inhibitors (ICI). Median follow up: 12.6 months; median treatment duration: 33 weeks. Overall ORR (N=98) was 61%, and among patients with prior ICI (n=15) was 60%. In patients with LDH>ULN (n=32), ORR, DCR, and mDOR were 53%, 72%, and NR (95% CI: 7–NE), respectively. In patients with liver metastases at baseline (n=21), ORR, DCR, and mDOR were 43%, 57%, and 9 months (95% CI: 3–NE), respectively. In patients with any M1c disease and LDH>ULN at baseline (n=17), ORR, DCR, mDOR were 35%, 59%, and NR (95% CI: 6–NE), respectively. Overall, 44% of patients reported grade ≥3 TEAEs and 33% reported serious TEAEs.

Conclusions: Fianlimab plus cemiplimab showed high activity in patients with advanced melanoma and poor prognosis features at baseline; ORR and DCR observed compare positively with available data for approved ICI combinations in the same clinical setting. A Phase 3 trial (NCT05352672) of fianlimab plus cemiplimab in treatment-naïve advanced melanoma patients is ongoing.