A phase I study of TAK-659 and paclitaxel in patients with taxane-refractory advanced solid tumors.

Autor:	Gouda MA; Department of Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, Houston., Shunyakova J; Department of Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, Houston., Naing A; Department of Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, Houston., Dumbrava E; Department of Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, Houston., Hong DS; Department of Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, Houston., Yuan Y; Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston., Yang P; Department of Palliative, Rehabilitation, and Integrative Medicine, The University of Texas MD Anderson Cancer Center, Houston., Myers A; Department of Diagnostic and Biomedical Sciences, School of Dentistry, The University of Texas Health Science Center at Houston, Houston, USA., Liang Y; Department of Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, Houston., Peng J; Department of Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, Houston., Karp D; Department of Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, Houston., Tsimberidou AM; Department of Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, Houston., Rodon J; Department of Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, Houston., Yap TA; Department of Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, Houston., Piha-Paul SA; Department of Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, Houston., Meric-Bernstam F; Department of Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, Houston., Fu S; Department of Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, Houston. Electronic address: siqingfu@mdanderson.org.
Jazyk:	angličtina
Zdroj:	ESMO open [ESMO Open] 2024 Jun; Vol. 9 (6), pp. 103486. Date of Electronic Publication: 2024 Jun 08.
DOI:	10.1016/j.esmoop.2024.103486
Abstrakt:	Background: Paclitaxel resistance limits durability of response in patients with initial clinical benefit. Overexpression of spleen tyrosine kinase (SYK) has been proposed as a possible resistance mechanism. This phase I trial evaluated the safety and preliminary activity of the SYK inhibitor TAK-659 combined with paclitaxel in patients with advanced taxane-refractory solid tumors. Patients and Methods: Patients with advanced solid tumors and prior progression on taxane-based therapy received intravenous infusion of paclitaxel on days 1, 8, and 15 plus oral TAK-659 daily in 28-day cycles. The dose-escalation phase included six cohorts treated at different dose levels; the dose-expansion phase included patients with ovarian cancer treated at the highest dose level. Toxicity was graded using the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0. Efficacy was evaluated using Response Evaluation Criteria in Solid Tumors version 1.1. Results: Our study included 49 patients. Maximum tolerated dose was not reached, but higher rates of adverse events were observed at higher dose levels. There were no treatment-related deaths. The most common treatment-related adverse events of any grade were increased aspartate aminotransferase (n = 31; 63%), increased alanine aminotransferase (n = 26; 53%), decreased neutrophil count (n = 26; 53%), and decreased white blood cell count (n = 26; 53%). Most adverse events were either grade 1 or 2. In the 44 patients with evaluable disease, 12 (27%) had stable disease as the best overall response, including three patients with prolonged stable disease, and 4 patients (9%) achieved a partial response. Conclusions: The combination of paclitaxel and TAK-659 showed preliminary activity possibly overcoming resistance to taxane-based therapy as well as a tolerable safety profile in patients with advanced solid tumors. (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)
Databáze:	MEDLINE
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