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

• Published in: Journal of clinical oncology Vol. 38; no. 11; pp. 1154 - 1163
• Main Authors: Taylor, Matthew H, Lee, Chung-Han, Makker, Vicky, Rasco, Drew, Dutcus, Corina E, Wu, Jane, Stepan, Daniel E, Shumaker, Robert C, Motzer, Robert J
• Format: Journal Article
• Language: English
• Published: United States American Society of Clinical Oncology 10.04.2020
• Subjects: Adult; Aged; Aged, 80 and over; Antibodies, Monoclonal, Humanized - administration & dosage; Antibodies, Monoclonal, Humanized - adverse effects; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Carcinoma, Renal Cell - drug therapy; Cohort Studies; Endometrial Neoplasms - drug therapy; Female; Humans; Kidney Neoplasms - drug therapy; Male; Maximum Tolerated Dose; Melanoma - drug therapy; Middle Aged; Neoplasms - drug therapy; ORIGINAL REPORTS; Phenylurea Compounds - administration & dosage; Phenylurea Compounds - adverse effects; Quinolines - administration & dosage; Quinolines - adverse effects
• ISSN: 0732-183X; 1527-7755
• DOI: 10.1200/JCO.19.01598

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. 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 (ORR ) at the recommended phase II dose. 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. ORR 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%). Lenvatinib plus pembrolizumab demonstrated a manageable safety profile and promising antitumor activity in patients with selected solid tumor types.