Poster Presentation Clinical Oncology Society of Australia Annual Scientific Meeting 2023

Significant durable response with fianlimab (anti-LAG-3) and cemiplimab (anti-PD-1) in advanced melanoma: post-adjuvant PD-1 analysis (#206)

Omid Hamid 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 , 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 , Laura Brennan 15 , Vladimir Jankovic 15 , Anne Paccaly 15 , Sheila Masinde 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: In two cohorts with advanced PD-(L)1 naïve metastatic melanoma, an ORR of 63.8% was previously reported with anti-LAG-3 (fianlimab) + anti-PD-1 (cemiplimab) treatment (NCT03005782); we present Phase 1 safety and clinical activity data, including patients who received prior adjuvant systemic treatment.

Methods: The analysis population included three expansion cohorts with unresectable/metastatic melanoma who were anti-PD-(L)1 treatment-naïve for advanced disease. Patients received fianlimab 1600 mg + cemiplimab 350 mg intravenously Q3W for 12 months, plus a further 12 months if clinically indicated.

Results: 98 patients were enrolled and treated (Nov 1, 2022 data cutoff); 2% had received prior metastatic treatment (not anti-PD-(L)1) and 24% prior adjuvant/neoadjuvant treatment (anti-PD-1, 13%), with 6 months’ disease-free interval. Median follow up was 12.6 months; median treatment duration was 33 weeks. Grade ≥3 TEAEs, serious TEAEs, and irAEs occurred in 44%, 33%, and 65% of patients, respectively; 16% of patients discontinued treatment due to TEAEs. Rates of irAEs were similar to rates for anti-PD-1 monotherapy, except for adrenal insufficiency (all grades, 11%; grade ≥3, 4%). Overall ORR was 61% (60/98; CR, n=12; PR, n=48), with mDOR NR (95% CI: 23–NE). KM estimation of mPFS was 15 (95% CI: 9–NE) months. In patients with any prior adjuvant treatment, ORR, mDOR, and mPFS were 61% (14/23), NR, and 13 months, respectively. In patients with prior anti-PD-1 adjuvant treatment, ORR, mDOR, and mPFS were 62% (8/13), NR, and 12 months, respectively.

Conclusions: In advanced melanoma patients, fianlimab + cemiplimab showed high clinical activity that compares favorably with other approved combinations of immune checkpoint inhibitors in the same clinical setting. This is the first indication that dual LAG-3 blockade can produce high levels of activity following adjuvant anti-PD-1 treatment. A Phase 3 trial (NCT05352672) of fianlimab + cemiplimab in treatment-naïve patients with advanced melanoma is ongoing.