Phase IB/II trial of lenvatinib plus pembrolizumab in patients with advanced renal cell carcinoma, endometrial cancer, and other selected advanced solid tumors Journal Article
| Authors: | Taylor, M. H.; Lee, C. H.; Makker, V.; Rasco, D.; Dutcus, C. E.; Wu, J.; Stepan, D. E.; Shumaker, R. C.; Motzer, R. J. |
| Article Title: | Phase IB/II trial of lenvatinib plus pembrolizumab in patients with advanced renal cell carcinoma, endometrial cancer, and other selected advanced solid tumors |
| 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. |
| Journal Title: | Journal of Clinical Oncology |
| Volume: | 38 |
| Issue: | 11 |
| ISSN: | 0732-183X |
| Publisher: | American Society of Clinical Oncology |
| Date Published: | 2020-04-10 |
| Start Page: | 1154 |
| End Page: | 1163 |
| Language: | English |
| DOI: | 10.1200/jco.19.01598 |
| PUBMED: | 31961766 |
| PROVIDER: | scopus |
| PMCID: | PMC7145588 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 1 May 2020 -- Source: Scopus |
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