Lenvatinib plus pembrolizumab versus standard of care in recurrent/metastatic head and neck squamous cell carcinoma: Randomized, phase 2 LEAP-009 trial

PURPOSE: Safe and effective treatment options are needed for patients with recurrent/metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) that has progressed after first-line platinum-based therapy and a PD-(L)1 inhibitor. We present results from the phase 2 LEAP-009 study (NCT04428151) of lenvatinib-pembrolizumab versus standard of care (SOC) or lenvatinib monotherapy in R/M HNSCC. PARTICIPANTS AND METHODS: Adults with confirmed R/M HNSCC and radiographic disease progression ≤ 12 weeks from last dose of treatment (≥2 doses of anti-PD-[L]1 therapy during or after platinum-containing chemotherapy) were randomized 3:3:2 to oral lenvatinib 20 mg once daily plus intravenous pembrolizumab 200 mg every 3 weeks (≤35 cycles), investigator's choice of SOC treatment (chemotherapy or cetuximab), or oral lenvatinib 24 mg once daily. The primary endpoint was overall survival (OS) with lenvatinib-pembrolizumab versus SOC. Secondary endpoints included safety. Efficacy of lenvatinib was exploratory. RESULTS: Overall, 374 participants were assigned to lenvatinib-pembrolizumab (n = 144), SOC (n = 142), or lenvatinib (n = 88). Median study follow-up was 16.5 months (range, 0.1-45.1). Median OS was 8.4 months with lenvatinib-pembrolizumab and 11.3 months with SOC (HR, 1.48 [95% CI, 1.11-1.97]; P = 0.996), and 10.6 months with lenvatinib. Treatment-related adverse events led to treatment discontinuation of lenvatinib-pembrolizumab, SOC, and lenvatinib monotherapy in 16.8%, 8.6%, and 15.9% of participants; treatment-related deaths occurred in 5, 1, and 3 participants, respectively. CONCLUSIONS: Lenvatinib-pembrolizumab did not improve OS compared with SOC. More participants discontinued lenvatinib-pembrolizumab and lenvatinib monotherapy than SOC. Further research is needed to determine effective second-line treatments for this population.