Background: Lenvatinib (LEN) is a multikinase inhibitor of vascular endothelial growth factor receptor 1−3, fibroblast growth factor receptor 1−4, platelet-derived growth factor receptor α, RET, and KIT. Pembrolizumab (PEM) is an anti-PD-1 antibody approved for the second-line treatment of recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN) based on durable responses and an objective response rate (ORR) of 16% (Bauml J et al, J Clin Oncol 2017). We report initial results of the SCCHN cohort from a phase 1b/2 trial of the LEN + PEM combination (NCT02501096). Methods: In this multicenter, open-label study, patients (pts) with measurable, confirmed metastatic SCCHN and ECOG performance status ≤1 received LEN (20 mg/day orally) + PEM (200 mg Q3W, IV). Pts were not preselected based on PD-L1 status. Tumor assessments were performed by study investigators using immune-related RECIST (irRECIST). The phase 2 primary endpoint was ORR at 24 weeks (ORR_WK24). Secondary endpoints included ORR, progression-free survival (PFS), and duration of response (DOR), which is calculated for pts with complete or partial responses. Results: At data cutoff of August 1, 2017, 22 pts with SCCHN (regardless of PD-L1 status) were enrolled. 86% of pts had ≥1 prior anticancer therapy. Median follow-up for PFS was 7.6 months (95% confidence interval [CI], 4.2–12.6) per irRECIST. Efficacy outcomes are summarized in the table. Grade 3 or 4 AEs occurred in 91% of pts (grade 4 AEs in 14%). However, 4 (18%) discontinued study treatment due to AEs. The most common AEs were fatigue (55%), decreased appetite (41%), hypertension (41%), diarrhea (36%), and nausea (36%). Updated data will be presented. Conclusions: LEN + PEM demonstrated promising clinical activity and manageable toxicities, supporting further evaluation of the LEN + PEM combination in pts with SCCHN. Clinical trial information: NCT02501096

*8 partial responses (PR). ^†7 PRs, 1 complete response. ^‡4 of the 8 (50%) responders achieved a DOR of > 6 months.