Pembrolizumab With Axitinib in Recurrent Endometrial Cancer

Summary

The main purpose of this study is to see if adding the experimental medication, axitinib, to usual treatment with pembrolizumab will work better than pembrolizumab alone. The study team will look at overall safety and side effects of the combination of axitinib and pembrolizumab to see how well it is tolerated. Researchers will also want to take some research blood samples to explore what effects the combination of treatment has on participants' cells and immune system and to see if there are things in participants' blood that can predict a response or resistance to the combined treatment.

Timeline

Start

2021-02-01

Primary completion

2025-01-01

Completion

2026-12-01

Publications

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• Background Ozao-Choy J, Ma G, Kao J, Wang GX, Meseck M, Sung M, Schwartz M, Divino CM, Pan PY, Chen SH. The novel role of tyrosine kinase inhibitor in the reversal of immune suppression and modulation of tumor microenvironment for immune-based cancer therapies. Cancer Res. 2009 Mar 15;69(6):2514-22. doi: 10.1158/0008-5472.CAN-08-4709. Epub 2009 Mar 10.
• Background Kwilas AR, Ardiani A, Donahue RN, Aftab DT, Hodge JW. Dual effects of a targeted small-molecule inhibitor (cabozantinib) on immune-mediated killing of tumor cells and immune tumor microenvironment permissiveness when combined with a cancer vaccine. J Transl Med. 2014 Nov 13;12:294. doi: 10.1186/s12967-014-0294-y.
• Background Kwilas AR, Donahue RN, Tsang KY, Hodge JW. Immune consequences of tyrosine kinase inhibitors that synergize with cancer immunotherapy. Cancer Cell Microenviron. 2015;2(1):e677. doi: 10.14800/ccm.677.
• Background Laubli H, Muller P, D'Amico L, Buchi M, Kashyap AS, Zippelius A. The multi-receptor inhibitor axitinib reverses tumor-induced immunosuppression and potentiates treatment with immune-modulatory antibodies in preclinical murine models. Cancer Immunol Immunother. 2018 May;67(5):815-824. doi: 10.1007/s00262-018-2136-x. Epub 2018 Feb 27.
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• Background Stehle F, Schulz K, Fahldieck C, Kalich J, Lichtenfels R, Riemann D, Seliger B. Reduced immunosuppressive properties of axitinib in comparison with other tyrosine kinase inhibitors. J Biol Chem. 2013 Jun 7;288(23):16334-16347. doi: 10.1074/jbc.M112.437962. Epub 2013 Apr 26.
• Background Atkins MB, Plimack ER, Puzanov I, Fishman MN, McDermott DF, Cho DC, Vaishampayan U, George S, Olencki TE, Tarazi JC, Rosbrook B, Fernandez KC, Lechuga M, Choueiri TK. Axitinib in combination with pembrolizumab in patients with advanced renal cell cancer: a non-randomised, open-label, dose-finding, and dose-expansion phase 1b trial. Lancet Oncol. 2018 Mar;19(3):405-415. doi: 10.1016/S1470-2045(18)30081-0. Epub 2018 Feb 10.
• Background Rini BI, Plimack ER, Stus V, Gafanov R, Hawkins R, Nosov D, Pouliot F, Alekseev B, Soulieres D, Melichar B, Vynnychenko I, Kryzhanivska A, Bondarenko I, Azevedo SJ, Borchiellini D, Szczylik C, Markus M, McDermott RS, Bedke J, Tartas S, Chang YH, Tamada S, Shou Q, Perini RF, Chen M, Atkins MB, Powles T; KEYNOTE-426 Investigators. Pembrolizumab plus Axitinib versus Sunitinib for Advanced Renal-Cell Carcinoma. N Engl J Med. 2019 Mar 21;380(12):1116-1127. doi: 10.1056/NEJMoa1816714. Epub 2019 Feb 16.

Drugs

Indications