Background: Lenvatinib (LEN) is a multikinase inhibitor of VEGFR 1−3, FGFR 1−4, PDGFRα, RET, and KIT. Pembrolizumab (PEM), an anti-PD-1 antibody, is an approved monotherapy for previously treated patients (pts) with PD-L1 (+) (tumor proportion score ≥1%) metastatic non-small cell lung cancer (mNSCLC; objective response rate [ORR] 18%). We report interim results of an ongoing phase 1b/2 trial of LEN + PEM in pts with solid tumors, focusing on the mNSCLC cohort. Methods: In this multicenter, open-label study (NCT02501096), pts with measurable, confirmed mNSCLC, ECOG PS ≤1, ≤ 2 prior systemic therapies (phase 2 only) received oral LEN (20 mg/day) and PEM (200 mg Q3W, IV). Pts were not preselected by PD-L1 status. The phase 2 primary end point was ORR at 24 weeks (ORR_WK24) by investigator-assessed immune-related RECIST (irRECIST). Secondary end points included ORR, progression-free survival (PFS) and duration of response (DOR). Results: At data cutoff (March 1, 2018), 21 pts were enrolled: 9 (43%) PD-L1(+), 5 (24%) PD-L1(-), and 7 (33%) not tested. Pts were treatment-naïve (14%); or had 1 (33%), 2 (48%), or ≥3 (5%) prior lines of systemic therapy. ORR_WK24 was 33.3% (95% CI, 14.6–57.0); other efficacy outcomes are summarized in the table. Grade 3 and 4 treatment-related adverse events (TRAEs) occurred in 48% and 5% (increased aspartate aminotransferase) of pts. There was 1 fatal TRAE (exsanguination; “possibly related” to study treatment). The most common grade 3 TRAEs were hypertension (24%), fatigue (14%), diarrhea (14%), proteinuria (10%), and arthralgia (10%). Conclusions: LEN + PEM showed promising clinical activity and a manageable safety profile in previously treated pts with mNSCLC who were not preselected for PD-L1 status. Further study is warranted.

NE, not estimable.