Submitter Withdrawn Clinical Oncology Society of Australia Annual Scientific Meeting 2022

Phase 1 study of fianlimab, a human lymphocyte activation gene-3 (LAG-3) monoclonal antibody, plus cemiplimab in advanced melanoma (#205)

Omid Hamid 1 , Amy Weise 2 , Tae Min Kim 3 , Meredith McKean 4 , Nehal J Lakhani 5 , John Kaczmar 6 , Kyriakos P Papadopoulos 7 , Shuquan Chen 8 , Jayakumar Mani 8 , Vladimir Jankovic 8 , Glenn Kroog 8 , Tasha Sims 8 , Israel Lowy 8 , Giuseppe Gullo 8
  1. The Angeles Clinical and Research Institute, a Cedars-Sinai Affiliate, Los Angeles, CA, USA
  2. Henry Ford Hospital, Detroit, MI, USA
  3. Seoul National University Hospital, Seoul, South Korea
  4. Sarah Cannon Research Institute/Tennessee Oncology PLLC, Nashville, TN, USA
  5. START Midwest, Grand Rapids, MI, USA
  6. MUSC Hollings Cancer Center, North Charleston, SC, USA
  7. START San Antonio, San Antonio, TX, USA
  8. Regeneron Pharmaceuticals, Inc., Tarrytown, NY, USA

Background: Concurrent LAG-3 blockade may enhance efficacy of anti–programmed cell death-1 (PD-1) therapies such as cemiplimab. We present updated safety and clinical activity data from patients with advanced melanoma treated concurrently with cemiplimab and fianlimab (NCT03005782).

Methods: Patients were included with unresectable or metastatic melanoma (excluding uveal melanoma) who were anti–PD-ligand (L) 1 treatment naive (expansion cohort [EC] 6) or anti–PD-(L)1 experienced within 3 months of screening (EC7). Patients received fianlimab 1600 mg + cemiplimab 350 mg intravenously every 3 weeks for 12 months (optional extra 12 months if clinically indicated). Tumours were measured every 6 weeks for 24 weeks, then every 9 weeks. In EC6 (n=40) and EC7 (n=15), respectively (data cutoff 9 Feb 2022), median age was 69.5 and 59.0 years, and median treatment duration was 37.1 and 9.0 weeks.

Results: In EC6 and EC7, respectively, incidence of Grade ≥3 treatment-emergent adverse events (TEAEs) were 38% and 47%, incidence of serious TEAEs was 33% and 33%, and 18% and 13% of patients discontinued treatment due to a TEAE. Adrenal insufficiency rate was 13% and 7% in EC6 and EC7, respectively; no instances led to treatment discontinuation. Investigator-assessed objective response rate was 63% (6 complete responses; 19 partial responses) in EC6 and 13% (2 partial responses) in EC7. Kaplan-Meier estimate of median progression-free survival was 14.2 (95% CI: 5.6–not estimated) months in EC6 and 1.4 (95% CI: 1.3–7.7) months in EC7. Median duration of response was not reached in EC6 or EC7.

Conclusion: Fianlimab plus cemiplimab in advanced melanoma had a similar safety profile to anti–PD-1 monotherapies. Clinical activity in anti–PD-(L)1–naive patients appeared higher than previously reported for anti–PD-1 monotherapy or anti–LAG-3 plus anti–PD-1. A Phase 3 trial (NCT05352672) investigating fianlimab plus cemiplimab in advanced melanoma is ongoing.