Abstract PO-003: Lenvatinib with or without pembrolizumab versus chemotherapy for treatment of recurrent or metastatic head and neck squamous cell carcinoma that progressed on platinum therapy and immunotherapy: Phase 2 LEAP-009
Authors: Harrington Kevin J. , Kim Hye Ryun , Salas Sebastien , Oliva Marc , Metcalf Robert , Bernsdorf Mogens , Kim Ji-Won , Cohen Ezra E. W. , Siu Lillian , Rischin Danny , Licitra Lisa , Vermorken Jan , Le Quynh , Tahara Makoto , Machiels Jean-Pascal , O'Hara Karen , Pathiraja Kumudu , Gumuscu Burak , Bidadi Behzad , Burtness Barbara 
Published: September 2023

Introduction: Pembrolizumab monotherapy and pembrolizumab plus platinum-based chemotherapy are the standard of care for first-line treatment of recurrent/metastatic (R/M) head and neck squamous cell carcinoma (HNSCC). Pembrolizumab plus lenvatinib showed promising antitumor activity and manageable safety in metastatic HNSCC in the phase 1b/2 Study 111/KEYNOTE-146 trial. The randomized, open-label, phase 2 LEAP-009 (NCT04428151) study is designed to evaluate the safety and efficacy of lenvatinib plus pembrolizumab or lenvatinib monotherapy versus chemotherapy in R/M HNSCC upon progression after treatment with platinum-based therapy and a PD-1/L1 inhibitor. Materials and Methods: Eligible patients have locally incurable, histologically confirmed R/M HNSCC (of the oral cavity, oropharynx, hypopharynx, and/or larynx), ECOG PS of 0 or 1, no ulceration and/or fungation of disease on skin, and disease progression on or after platinum-based therapy (with/without cetuximab) and PD-1/L1 inhibitor (progression must be within 12 weeks from last dose and patients must have received ≥2 doses). Patients will be randomly assigned 3:3:2 to receive oral lenvatinib 20 mg every day plus pembrolizumab 200 mg IV every 3 weeks (≤35 pembrolizumab cycles), standard-of-care chemotherapy (investigator’s choice of docetaxel, paclitaxel, cetuximab, or capecitabine), or oral lenvatinib monotherapy 24 mg every day. Treatment will continue until centrally verified disease progression, unacceptable toxicity, or withdrawal. Patients who experience centrally verified disease progression in chemotherapy or lenvatinib monotherapy arms may cross over to lenvatinib plus pembrolizumab at time of disease progression with sponsor consultation. Randomization will be stratified by PD-L1 tumor proportion score (&lt;50% vs ≥50%) and ECOG PS (0 vs 1). Imaging will be performed every 6 weeks through year 1 and every 9 weeks thereafter. Response will be assessed per RECIST v1.1 by blinded independent central review. Safety will be monitored throughout the study and for 30 days following treatment end (90 days for serious AEs) and graded per NCI CTCAE v5.0. The primary end point is objective response rate and secondary end points are progression-free survival, duration of response, overall survival, and safety. Results: Planned enrollment is approximately 400, and recruitment is currently underway in Asia, Australia, Europe, and North America. Conclusion: Results of LEAP-009 will provide clarity on the efficacy and safety of lenvatinib with or without pembrolizumab versus chemotherapy for patients with R/M HNSCC upon progression after platinum and immunotherapy.

Citation Format: Kevin J. Harrington, Hye Ryun Kim, Sebastien Salas, Marc Oliva, Robert Metcalf, Mogens Bernsdorf, Ji-Won Kim, Ezra E. W. Cohen, Lillian Siu, Danny Rischin, Lisa Licitra, Jan Vermorken, Quynh Le, Makoto Tahara, Jean-Pascal Machiels, Karen O'Hara, Kumudu Pathiraja, Burak Gumuscu, Behzad Bidadi, Barbara Burtness. Lenvatinib with or without pembrolizumab versus chemotherapy for treatment of recurrent or metastatic head and neck squamous cell carcinoma that progressed on platinum therapy and immunotherapy: Phase 2 LEAP-009 [abstract]. In: Proceedings of the AACR-AHNS Head and Neck Cancer Conference: Innovating through Basic, Clinical, and Translational Research; 2023 Jul 7-8; Montreal, QC, Canada. Philadelphia (PA): AACR; Clin Cancer Res 2023;29(18_Suppl):Abstract nr PO-003.