Journal Article
. 2020 Jan; 38(11):1154-1163.
doi: 10.1200/JCO.19.01598.

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 1 Chung-Han Lee 2 Vicky Makker 2 Drew Rasco 3 Corina E Dutcus 4 Jane Wu 4 Daniel E Stepan 5 Robert C Shumaker 4 Robert J Motzer 2 
  • PMID: 31961766
  •     30 References
  •     76 citations


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.

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Yunchao Wang, Xiaobo Yang, +9 authors, Haitao Zhao.
Front Oncol, 2022 Mar 22; 12. PMID: 35311147    Free PMC article.
An Update on the Immunotherapy for Oropharyngeal Squamous Cell Carcinoma.
Yaxuan Huang, Yunyun Lan, +2 authors, Tingting Huang.
Front Oncol, 2022 Apr 05; 12. PMID: 35372036    Free PMC article.
Immune Checkpoint Inhibitor-Based Systemic Therapy Shows Remarkable Curative Effect in a Hepatocellular Carcinoma Patient With Intractable Postoperative Recurrence and Metastases: A Case Report and Literature Review.
Xing He, Yaorong Peng, Zhenyu Zhou, Wenbin Li.
Front Oncol, 2022 Apr 05; 12. PMID: 35372050    Free PMC article.
Cancer combination therapies by angiogenesis inhibitors; a comprehensive review.
Mohammad Javed Ansari, Dmitry Bokov, +9 authors, Mehdi Dadashpour.
Cell Commun Signal, 2022 Apr 09; 20(1). PMID: 35392964    Free PMC article.
Molecularly Targeted Therapy towards Genetic Alterations in Advanced Bladder Cancer.
Jonathan Thomas, Guru Sonpavde.
Cancers (Basel), 2022 Apr 13; 14(7). PMID: 35406567    Free PMC article.
Solid Tumors and Kinase Inhibition: Management and Therapy Efficacy Evolution.
Flávia Melo Cunha de Pinho Pessoa, Caio Bezerra Machado, +7 authors, Caroline Aquino Moreira-Nunes.
Int J Mol Sci, 2022 Apr 13; 23(7). PMID: 35409190    Free PMC article.
Anti-angiogenesis revisited: reshaping the treatment landscape of advanced non-small cell lung cancer.
Sun Ha Choi, Seung Soo Yoo, Shin Yup Lee, Jae Yong Park.
Arch Pharm Res, 2022 Apr 23; 45(4). PMID: 35449345
Synergistic Anti-Angiogenic Effect of Combined VEGFR Kinase Inhibitors, Lenvatinib, and Regorafenib: A Therapeutic Potential for Breast Cancer.
Khuloud Bajbouj, Rizwan Qaisar, +9 authors, Adel B Elmoselhi.
Int J Mol Sci, 2022 Apr 24; 23(8). PMID: 35457226    Free PMC article.
Melanoma Brain Metastases: An Update on the Use of Immune Checkpoint Inhibitors and Molecularly Targeted Agents.
Stergios J Moschos.
Am J Clin Dermatol, 2022 May 10;. PMID: 35534670