Poster Presentation Clinical Oncology Society of Australia Annual Scientific Meeting 2023

A Phase 3 trial comparing fianlimab (anti-LAG-3) plus cemiplimab (anti-PD-1) to pembrolizumab in patients with completely resected high-risk melanoma (#512)

John Crown 1 , Timothy J. Panella 2 , Sajeve S. Thomas 3 , Meredith McKean 4 , Kim Margolin 5 , Ryan Weight 6 , Giuseppe Gullo 7 , Jayakumar Mani 7 , Shraddha Patel 7 , Priya Desai 7 , Mark Salvati 7 , Israel Lowy 7 , Matthew G. Fury 7 , Karl D. Lewis 7
  1. St Vincent’s University Hospital, Dublin, Ireland
  2. University of Tennessee Medical Center, Knoxville, TN, USA
  3. Orlando Health Cancer Institute, Lake Mary, FL, USA
  4. Sarah Cannon Research Institute/Tennessee Oncology PLLC, Nashville, TN, USA
  5. Saint John's Cancer Institute, Santa Monica, CA, USA
  6. The Melanoma and Skin Cancer Institute, Denver, CO, USA
  7. Regeneron Pharmaceuticals, Inc., Tarrytown, NY, USA

Most patients with newly diagnosed melanoma have resectable disease and are potentially cured by surgery. However, regional nodal and/or distant relapses can occur after curative-intent resection. Postoperative adjuvant therapy with immune checkpoint inhibitors improves RFS and DMFS in patients at high risk of melanoma. Fianlimab (anti-LAG-3) and cemiplimab (anti-PD-1) are high-affinity, fully human monoclonal antibodies that, combined, have shown high clinical activity in patients with advanced melanoma. The combination of relatlimab (anti-LAG-3) and nivolumab (anti-PD-1) has also shown superiority over nivolumab in advanced melanoma. These observations provide a rationale for use of fianlimab plus cemiplimab for 1L metastatic melanoma (Phase 3 study, NCT05352672) and high-risk adjuvant melanoma (presented in this abstract).

This three-way, double-blind, Phase 3 international trial (NCT05608291) will compare fianlimab + cemiplimab with pembrolizumab as adjuvant therapy in high-risk, resected melanoma. Key eligibility criteria: aged ≥12 years; Stage IIc, III, or IV (all M-stages) histologically confirmed melanoma resected ≤12 weeks before randomization; no systemic anticancer or radiation adjuvant therapy for melanoma within 5 years; no evidence of metastatic disease; ECOG PS 0/1 (adults), Karnofsky PS >70 (≥16 years), or Lansky PS >70 (<16 years).

About 1,530 patients will be randomized 1:1:1 to Arms A, B, or C and receive study treatment Q3W intravenously for 1 year: Arm A, cemiplimab + fianlimab dose 1; Arm B, cemiplimab + fianlimab dose 2; Arm C, pembrolizumab + placebo. The trial will be stratified by disease stage (IIIA vs. IIC-IIIB-IIIC vs. IIID-IV [M1a/b] vs. IV [M1c/d]), and geographical location (North America vs. Europe vs. Rest of World). The primary endpoint is investigator-assessed RFS. Secondary endpoints include efficacy (OS, DMFS, melanoma-specific survival), safety (TEAEs, interruption or discontinuation of drugs due to TEAEs), pharmacokinetics, immunogenicity, and patient-reported outcomes. First analysis will be performed when 242 RFS events have been observed.