Poster Presentation Clinical Oncology Society of Australia Annual Scientific Meeting 2022

LEAP-009: Phase 2 study of Lenvatinib with or without Pembrolizumab vs chemotherapy for the treatment of recurrent or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) upon progression after platinum and immunotherapy (PD-1/PD-L1 Inhibition) (#204)

Kevin J. Harrington 1 , Hye Ryun Kim 2 , Sebastien Salas 3 , Marc Oliva 4 , Robert Metcalf 5 , Mogens Bernsdorf 6 , Ji-Won Kim 7 , Ezra E. W. Cohen 8 , Lillian Siu 9 , Danny Rischin 10 , Lisa Licitra 11 , Jan Vermorken 12 , Quynh Le 13 , Makoto Tahara 14 , Jean-Pascal Machiels 15 , Karen O’Hara 16 , Kumudu Pathiraja 17 , Burak Gumuscu 17 , Behzad Bidadi 17 , Barbara Burtness 18 , Elani Bowers 19
  1. Institute of Cancer Research and The Royal Marsden NHS Foundation Trust, National Institute for Health and Care Research Biomedical Research Centre, London, United Kingdom
  2. Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, South Korea
  3. CHU Timone, Marseille, France
  4. Institut Català d’Oncologia, Barcelona, Spain
  5. The Christie NHS Foundation Trust, Manchester, United Kingdom
  6. Rigshospitalet, Copenhagen, Denmark
  7. Seoul National University Bundang Hospital, Seongnam, South Korea
  8. UC San Diego Health Moores Cancer Center, La Jolla, CA, USA
  9. Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada
  10. Peter MacCallum Cancer Centre, Melbourne, VIC, Australia
  11. Fondazione IRCCS Istituto Nazionale dei Tumori and University of Milan, Milan, Italy
  12. Antwerp University Hospital, Edegem, Belgium
  13. Stanford University, Stanford, CA, USA
  14. National Cancer Center Hospital East, Kashiwa, Japan
  15. Cliniques Universitaires Saint-Luc, Woluwe-Saint-Lambert, Belgium
  16. Eisai Inc., Nutley, NJ, USA
  17. Merck & Co., Inc., Rahway, NJ, USA
  18. Yale Cancer Center, New Haven, CT, USA
  19. MSD, Melbourne, VIC, Australia

Aims: The open-label, phase 2 LEAP-009 (NCT04428151) study is designed to evaluate the safety and efficacy of lenvatinib + pembrolizumab or lenvatinib monotherapy versus chemotherapy in R/M HNSCC after progression on platinum-based therapy and a PD-1/PD-L1 inhibitor.

Methods: Approximately 400 adults with locally incurable, histologically confirmed R/M HNSCC (of the oral cavity, oropharynx, hypopharynx, and/or larynx) will be randomly assigned 3:3:2 to lenvatinib 20 mg PO QD + pembrolizumab 200 mg IV Q3W (≤35 pembrolizumab cycles), standard-of-care chemotherapy (investigator’s choice of docetaxel, paclitaxel, cetuximab, or capecitabine), or lenvatinib monotherapy 24 mg PO QD. Patients must have an ECOG PS of 0 or 1, no ulceration and/or fungation of disease on skin, disease progression on or after platinum-based therapy (± cetuximab) and PD-1/PD-L1 inhibitor (progression ≤12 weeks from last dose; received ≥2 doses). Treatment continues until centrally verified disease progression, unacceptable toxicity, or withdrawal. Participants who experience centrally verified disease progression in chemotherapy or lenvatinib monotherapy arms can cross over to lenvatinib + pembrolizumab at time of disease progression with sponsor consultation. Stratification factors are PD-L1 tumor proportion score (<50% vs ≥50%) and ECOG PS (0 vs 1). Imaging will be performed Q6W through year 1 and Q9W thereafter. Response will be assessed per RECIST v1.1 by blinded independent central review. Safety will be monitored until 30 days following treatment end (90 days for serious AEs). The primary end point is objective response rate. Secondary end points are progression-free survival, duration of response, overall survival, and safety.  

Results: LEAP-009 is enrolling patients in North America, Europe, Asia, and Australia. Recruitment is currently underway.

Conclusion: Results of LEAP-009 will provide clarification on the efficacy and safety of lenvatinib with or without pembrolizumab vs chemotherapy for patients with R/M HNSCC upon progression after platinum and immunotherapy.

Clinical trial registration: NCT04428151