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https://www.readbyqxmd.com/read/30002191/alk-fusion-partners-impact-response-to-alk-inhibition-differential-effects-on-sensitivity-cellular-phenotypes-and-biochemical-properties
#1
Merrida A Childress, Stephen M Himmelberg, Huiqin Chen, Wanleng Deng, Michael A Davies, Christine M Lovly
Oncogenic tyrosine kinase fusions involving the anaplastic lymphoma kinase (ALK) are detected in numerous tumor types. Although more than 30 distinct 5' fusion partners have been reported, treatment of ALK-rearranged cancers is generally decided without regard to which 5' partner is present. There is little data addressing how the 5' partner affects the biology of the fusion or responsiveness to ALK tyrosine kinase inhibitors (TKIs). Based on the hypothesis that the 5' partner influences the intrinsic properties of the fusion protein, cellular functions that impact oncogenic potential, and sensitivity to ALK TKIs; clonal 3T3 cell lines stably expressing seven different ALK fusion variants were generated...
July 12, 2018: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/29563138/ensartinib-x-396-in-alk-positive-non-small-cell-lung-cancer-results-from-a-first-in-human-phase-i-ii-multicenter-study
#2
Leora Horn, Jeffrey R Infante, Karen L Reckamp, George R Blumenschein, Ticiana A Leal, Saiama N Waqar, Barbara J Gitlitz, Rachel E Sanborn, Jennifer G Whisenant, Liping Du, Joel W Neal, Jon P Gockerman, Gary Dukart, Kimberly Harrow, Chris Liang, James J Gibbons, Allison Holzhausen, Christine M Lovly, Heather A Wakelee
Purpose: Evaluate safety and determine the recommended phase II dose (RP2D) of ensartinib (X-396), a potent anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitor (TKI), and evaluate preliminary pharmacokinetics and antitumor activity in a first-in-human, phase I/II clinical trial primarily in patients with non-small cell lung cancer (NSCLC). Patients and Methods: In dose escalation, ensartinib was administered at doses of 25 to 250 mg once daily in patients with advanced solid tumors; in dose expansion, patients with advanced ALK -positive NSCLC were administered 225 mg once daily...
June 15, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29506392/background-and-rationale-of-the-exalt3-trial-investigating-x-396-in-the-treatment-of-alk-non-small-cell-lung-cancer
#3
Eric K Singhi, Leora Horn
Despite significant advancements in the treatment of anaplastic lymphoma kinase (ALK) positive non-small-cell lung cancer (NSCLC) since the advent of crizotinib, the development of acquired resistance and poor CNS efficacy have necessitated the search for novel and more robust therapies. Ensartinib (X-396) is a novel second-generation ALK-tyrosine kinase inhibitor (TKI) that holds much clinical promise. Preclinical data have demonstrated increased potency of the drug as compared with crizotinib and other second-generation ALK-TKI therapies such as alectinib and ceritinib...
March 6, 2018: Future Oncology
https://www.readbyqxmd.com/read/27969449/mini01-02-response-and-plasma-genotyping-from-phase-i-ii-trial-of-ensartinib-x-396-in-patients-pts-with-alk-nsclc-topic-medical-oncology
#4
Leora Horn, Heather Wakelee, Karen L Reckamp, George Blumenschein, Jeffrey R Infante, Corey A Carter, Saiama N Waqar, Joel W Neal, Kimberly Harrow, Jon P Gockerman, Gary Dukart, Chris Liang, James L Gibbons, Jennifer Hernandez, Tera Newman-Eerkes, Lee Lim, Christine M Lovly
No abstract text is available yet for this article.
November 2016: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/27682212/current-and-developing-therapies-for-the-treatment-of-non-small-cell-lung-cancer-with-alk-abnormalities-update-and-perspectives-for-clinical-practice
#5
REVIEW
M Caccese, R Ferrara, S Pilotto, L Carbognin, G Grizzi, A Caliò, M Brunelli, F Cuppone, S Petraglia, A Scarpa, G Tortora, E Bria
The treatment of patients with ALK-rearranged non-small-cell lung cancer was completely revolutionized by the introduction of Crizotinib, a small molecule inhibiting ALK, MET and ROS1. Given that resistance occurs within approximately 12 months, in order to develop more potent inhibitors and to increase drug penetration to CNS, innovative ALK-inhibitors were developed. Second-generation ALK inhibitors Ceritinib (LDK378), Alectinib (CH5424802/RO5424802) and Brigatinib (AP26113) have shown significant clinical activity, and were rapidly approved by regulatory agencies...
December 2016: Expert Opinion on Pharmacotherapy
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