A phase Ib/II trial of lenvatinib (LEN) plus pembrolizumab (Pembro) in patients (Pts) with endometrial carcinoma

5598 Background: LEN is a multikinase inhibitor of vascular endothelial growth factor (VEGF) receptor 1−3, fibroblast growth factor receptor 1−4, platelet-derived growth factor receptor α, RET, and KIT. Pembro, an antibody targeting programmed cell death protein 1 (PD-1), prevents T cell deactivation. In addition to its antiangiogenic effects, LEN may act in part by preventing VEGF-mediated immune suppression, suggesting combination with pembro could improve its activity. We report results in pts with endometrial carcinoma from a phase Ib/II trial of LEN + pembro. Methods: In this multicenter, open-label study, pts had confirmed metastatic endometrial cancer that progressed after approved therapy, measurable disease, and ECOG performance status ≤ 1. Pts received oral LEN 20 mg/day plus pembro 200 mg intravenously every 3 weeks. Tumor assessments were by the investigator. The primary phase II endpoint was objective response rate (ORR) based on immune-related RECIST (irRECIST). Secondary endpoints included progression-free survival (PFS), disease-control rate (DCR; complete response [CR] + partial response [PR] + stable disease [SD]), clinical-benefit rate (CBR; CR + PR + durable SD), and duration of response (DOR), all by irRECIST, and safety. Results: 23 Pts enrolled (phase II: 21; phase Ib: 2); median age was 64 years (range: 51−80); 87% were white; and all had ≥ 1 prior anticancer therapy. Confirmed ORR was 48% (all PR). Median PFS and DOR were not estimable (NE; see table). All pts had a treatment-emergent adverse event (TEAE). The most common TEAEs were hypertension, fatigue, arthralgia, diarrhea, and nausea. Toxicities were manageable with dose interruption and/or modification and no new safety signals were found. Updated data will be presented. Conclusions: Promising efficacy was observed in pts receiving LEN + pembro. In addition, toxicities were generally expected and manageable with dose modification. These results warrant further study of LEN + pembro in pts with endometrial carcinoma. Clinical trial information: NCT02501096. [Table: see text]