3627 - Safety and Activity Profile of Fianlimab (Anti-LAG-3) in Combination With Cemiplimab (Anti-PD-1) and Cemiplimab Monotherapy in Recurrent and/or Metastatic HNSCC

B. C. Cho¹, K. Harrington², B. Keam³, K. P. Papadopoulos⁴, O. Hamid⁵, X. Zhu⁶, J. Kaczmar⁷, S. Williamson⁸, and A. Kong^9,10; ¹Division of Medical Oncology, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Korea, Republic of (South), ²The Institute of Cancer Research/Royal Marsden NHS Foundation Trust, London, United Kingdom, ³Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea, Republic of (South), ⁴START San Antonio, San Antonio, TX, ⁵The Angeles Clinic and Research Institute, a Cedars-Sinai Affiliate, Los Angeles, CA, ⁶Zuckerberg Cancer Center, Northwell Health Cancer Institute, New Hyde Park, NY, ⁷MUSC Hollings Cancer Center, North Charleston, SC, ⁸University of Kansas Medical Center, Kansas City, KS, ⁹Institute of Cancer and Genomic Sciences, University of Birmingham, Birmingham, United Kingdom, ¹⁰Comprehensive Cancer Centre, King’s College London, London, United Kingdom

Purpose/Objective(s): Anti–PD-1 is approved for the treatment of recurrent and/or metastatic (R/M) head and neck squamous cell carcinomas (HNSCC), but the benefit is modest. Concurrent blockade of LAG-3 may enhance the efficacy of anti–PD-1 therapies. We assessed the biomarkers of cemiplimab monotherapy (not reported here) as well as the safety and activity profile of cemiplimab (anti–PD-1) monotherapy and fianlimab (anti–LAG-3) + cemiplimab in patients (pts) who were anti–PD-1-naïve for R/M HNSCC. Materials/

Methods: We report part of the results of the exploratory tumor biopsy-driven Phase 1b study (NCT03198130) of cemiplimab monotherapy and the Phase 1 study (NCT03005782) of fianlimab + cemiplimab combination in adult anti–PD-1-naïve pts with R/M HNSCC. In the Phase 1b biomarker study, pts were treated with cemiplimab 3 mg/kg IV Q2W for up to 48 weeks (wks); tumor measurements were performed every 8 wks. In the Phase 1 study, pts (expansion cohort) were treated with fianlimab 1600 mg + cemiplimab 350 mg IV Q3W for up to 24 months (m); tumor measurements were performed every 6 wks for 24 wks, then every 9 wks.
Results: In the Phase 1b biomarker study, 33 pts were enrolled and treated with cemiplimab. 88% of pts were male and 46% were White. 70% of pts had prior cancer-related systemic therapy. Median treatment duration was 15 wks and median follow-up was 4 m. Grade =3 treatment-emergent AEs (TEAEs) and serious TEAEs occurred in 39% and 18% of pts, respectively. Treatment-related TEAEs (TRAEs) were reported in 58% of pts. The most common TRAEs (any grade) were fatigue (18%), pruritus (18%), and hypothyroidism (15%). Grade =3 TRAEs occurred in 12% of pts. Treatment-related immune-related AEs (irAEs) were reported in 27% of pts. Investigator-assessed ORR was 24% (1 CR, 7 PRs). Disease control rate (DCR) was 52%, median PFS was 4 m (95% CI 2–6), and median duration of response (DOR) was 9 m (95% CI 4–16). In the Phase 1 study, 15 pts were enrolled and treated with fianlimab + cemiplimab. 80% of pts were male and 53% were White. All pts had received prior cancer-related systemic therapy. 33% (5/15) of pts had =2 prior lines of therapy. Median treatment duration was 12 wks and median follow-up was 12 m. Grade =3 TEAEs and serious TEAEs occurred in 47% and 13% of pts, respectively. TRAEs were reported in 67% of pts. The most common TRAE (any grade) was hypothyroidism (33%). Grade =3 TRAEs occurred in 7% of pts. Treatment-related irAEs were reported in 47% of pts. RECIST 1.1-based investigator-assessed ORR was 33% (5 PRs). DCR was 47%, median PFS was 2 m (95% CI 1–14), and DOR was 17, 10, 20, 22, and 20 m in 5 responders; median DOR was NR (95% CI 10–NE).
Conclusion: Cemiplimab monotherapy and fianlimab + cemiplimab combination demonstrated signs of clinical activity and an acceptable safety profile in anti–PD-1-naïve R/M HNSCC pts, warranting further investigation.