Phase IB/II Trial of Lenvatinib Plus Pembrolizumab in Patients With Advanced Renal Cell Carcinoma, Endometrial Cancer, and Other Selected Advanced Solid Tumors

Matthew H Taylor, Chung-Han Lee, Vicky Makker, Drew Rasco, Corina E Dutcus, Jane Wu, Daniel E Stepan, Robert C Shumaker, Robert J Motzer, Matthew H Taylor, Chung-Han Lee, Vicky Makker, Drew Rasco, Corina E Dutcus, Jane Wu, Daniel E Stepan, Robert C Shumaker, Robert J Motzer

Abstract

Purpose: Modulation of vascular endothelial growth factor-mediated immune suppression via angiogenesis inhibition may augment the activity of immune checkpoint inhibitors. We report results from the dose-finding and initial phase II expansion of a phase Ib/II study of lenvatinib plus pembrolizumab in patients with selected advanced solid tumors.

Methods: Eligible patients had metastatic renal cell carcinoma (RCC), endometrial cancer, squamous cell carcinoma of the head and neck (SCCHN), melanoma, non-small-cell lung cancer (NSCLC), or urothelial cancer. The primary objective of phase Ib was to determine the maximum tolerated dose (MTD) for lenvatinib plus pembrolizumab (200 mg intravenously every 3 weeks). In the preplanned phase II cohort expansion, the primary objective was objective response rate at week 24 (ORRweek 24) at the recommended phase II dose.

Results: Overall, 137 patients were enrolled during phase Ib (n = 13) and the initial phase II expansion (n = 124). Two dose-limiting toxicities (DLTs; grade 3 arthralgia and grade 3 fatigue) were reported in the initial dose level (lenvatinib 24 mg/d plus pembrolizumab). No DLTs were observed in the subsequent dose-de-escalation cohort, establishing the MTD and recommended phase II dose at lenvatinib 20 mg/d plus pembrolizumab. ORRweek24 was as follows: RCC, 63% (19/30; 95% CI, 43.9% to 80.1%); endometrial cancer, 52% (12/23; 95% CI, 30.6% to 73.2%); melanoma, 48% (10/21; 95% CI, 25.7% to 70.2%); SCCHN, 36% (8/22; 95% CI, 17.2% to 59.3%); NSCLC, 33% (7/21; 95% CI, 14.6% to 57.0%); and urothelial cancer 25% (5/20; 95% CI, 8.7% to 49.1%). The most common treatment-related adverse events were fatigue (58%), diarrhea (52%), hypertension (47%), and hypothyroidism (42%).

Conclusion: Lenvatinib plus pembrolizumab demonstrated a manageable safety profile and promising antitumor activity in patients with selected solid tumor types.

Trial registration: ClinicalTrials.gov NCT02501096.

Figures

FIG 1.
FIG 1.
Maximum change in target lesion size by tumor type (investigator review, immune-related RECIST). Arrows indicate patients from phase Ib treated with lenvatinib 24 mg/day.
FIG 2.
FIG 2.
Treatment response and duration for patients achieving a partial response or complete response (investigator review, immune-related RECIST). NSCLC, non–small-cell lung cancer; RCC, renal cell carcinoma; SCCHN, squamous cell carcinoma of the head and neck.

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Source: PubMed

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