A Trial of Lenvatinib (E7080) Plus Pembrolizumab in Participants With Selected Solid Tumors

Summary

This is an open-label Phase 1b/2 trial of lenvatinib (E7080) plus pembrolizumab in participants with selected solid tumors. Phase 1b will determine and confirm the maximum tolerated dose (MTD) for lenvatinib in combination with 200 milligrams (mg) (intravenous \[IV\], every 3 weeks \[Q3W\]) pembrolizumab in participants with selected solid tumors (i.e. non-small cell lung cancer, renal cell carcinoma, endometrial carcinoma, urothelial carcinoma, squamous cell carcinoma of the head and neck, melanoma or leiomyosarcoma). Phase 2 (Expansion) will evaluate the safety and efficacy of the combination in 7 cohorts at the MTD from Phase 1b (lenvatinib 20 mg/day orally + pembrolizumab 200 mg Q3W, IV).

Timeline

Start

2015-07-22

Primary completion

2020-08-18

Completion

2022-07-11

Publications

• Makker V, Taylor MH, Aghajanian C, Cohn AL, Brose MS, Simone CD, Cao ZA, Suttner L, Loboda A, Cristescu R, Jelinic P, Orlowski R, Dutta L, Matsui J, Dutcus CE, Minoshima Y, Messing MJ. Evaluation of potential biomarkers for lenvatinib plus pembrolizumab among patients with advanced endometrial cancer: results from Study 111/KEYNOTE-146. J Immunother Cancer. 2024 Jan 19;12(1):e007929. doi: 10.1136/jitc-2023-007929.
• Makker V, Aghajanian C, Cohn AL, Romeo M, Bratos R, Brose MS, Messing M, Dutta L, Dutcus CE, Huang J, Schmidt EV, Orlowski R, Taylor MH. A Phase Ib/II Study of Lenvatinib and Pembrolizumab in Advanced Endometrial Carcinoma (Study 111/KEYNOTE-146): Long-Term Efficacy and Safety Update. J Clin Oncol. 2023 Feb 10;41(5):974-979. doi: 10.1200/JCO.22.01021. Epub 2023 Jan 6.
• Lee CH, Shah AY, Rasco D, Rao A, Taylor MH, Di Simone C, Hsieh JJ, Pinto A, Shaffer DR, Girones Sarrio R, Cohn AL, Vogelzang NJ, Bilen MA, Gunnestad Ribe S, Goksel M, Tennoe OK, Richards D, Sweis RF, Courtright J, Heinrich D, Jain S, Wu J, Schmidt EV, Perini RF, Kubiak P, Okpara CE, Smith AD, Motzer RJ. Lenvatinib plus pembrolizumab in patients with either treatment-naive or previously treated metastatic renal cell carcinoma (Study 111/KEYNOTE-146): a phase 1b/2 study. Lancet Oncol. 2021 Jul;22(7):946-958. doi: 10.1016/S1470-2045(21)00241-2. Epub 2021 Jun 15.
• Lee CH, DiNatale RG, Chowell D, Krishna C, Makarov V, Valero C, Vuong L, Lee M, Weiss K, Hoen D, Morris L, Reznik E, Murray S, Kotecha R, Voss MH, Carlo MI, Feldman D, Sachdev P, Adachi Y, Minoshima Y, Matsui J, Funahashi Y, Nomoto K, Hakimi AA, Motzer RJ, Chan TA. High Response Rate and Durability Driven by HLA Genetic Diversity in Patients with Kidney Cancer Treated with Lenvatinib and Pembrolizumab. Mol Cancer Res. 2021 Sep;19(9):1510-1521. doi: 10.1158/1541-7786.MCR-21-0053. Epub 2021 May 26.
• Makker V, Taylor MH, Aghajanian C, Oaknin A, Mier J, Cohn AL, Romeo M, Bratos R, Brose MS, DiSimone C, Messing M, Stepan DE, Dutcus CE, Wu J, Schmidt EV, Orlowski R, Sachdev P, Shumaker R, Casado Herraez A. Lenvatinib Plus Pembrolizumab in Patients With Advanced Endometrial Cancer. J Clin Oncol. 2020 Sep 10;38(26):2981-2992. doi: 10.1200/JCO.19.02627. Epub 2020 Mar 13.
• Taylor MH, Lee CH, Makker V, Rasco D, Dutcus CE, Wu J, Stepan DE, Shumaker RC, Motzer RJ. Phase IB/II Trial of Lenvatinib Plus Pembrolizumab in Patients With Advanced Renal Cell Carcinoma, Endometrial Cancer, and Other Selected Advanced Solid Tumors. J Clin Oncol. 2020 Apr 10;38(11):1154-1163. doi: 10.1200/JCO.19.01598. Epub 2020 Jan 21.
• Makker V, Rasco D, Vogelzang NJ, Brose MS, Cohn AL, Mier J, Di Simone C, Hyman DM, Stepan DE, Dutcus CE, Schmidt EV, Guo M, Sachdev P, Shumaker R, Aghajanian C, Taylor M. Lenvatinib plus pembrolizumab in patients with advanced endometrial cancer: an interim analysis of a multicentre, open-label, single-arm, phase 2 trial. Lancet Oncol. 2019 May;20(5):711-718. doi: 10.1016/S1470-2045(19)30020-8. Epub 2019 Mar 25.

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