A phase 2, open-label, multi-center study of amuvatinib in combination with platinum etoposide chemotherapy in platinum-refractory small cell lung cancer patients

• Type of Material: Article
• Authors: Lauren Averett Byers, University of Texas; Leora Horn, Vanderbilt University; Jitendra Ghandi, Associates in Oncology and Hematology; Goetz Kloecker, University of Louisville; Taofeek Owonikoko, Emory University; Saiama Naheed Waqar, Washington University; Maciej Krzakowski, Centrum Onkologii-Instytut Im. M. Skłodowskiej-Curie w Warszawie; Robert J. Cardnell, University of Texas; Junya Fujimoto, University of Texas; Pietro Taverna, Astex Pharmaceuticals, Inc.; Mohammad Azab, Astex Pharmaceuticals, Inc.; David Ross Camidge, University of Colorado
• Language: English
• Date: 2017-10-06
• Publisher: Impact Journals
• Publication Version: Final Published Version
• Copyright Statement: © 2017 Byers et al.
• License: Creative Commons Attribution 3.0 Unported
• Final Published Version (URL): http://dx.doi.org/10.18632/oncotarget.19888
• Title of Journal or Parent Work: Oncotarget
• ISSN: 1949-2553
• Volume: 8
• Issue: 46
• Start Page: 81441
• End Page: 81454
• Grant/Funding Information: This work was supported by the MD Anderson Cancer Center Support Grant NIH/NCI award number P30CA016672, and an MD Anderson Cancer Center Physician Scientist Award (LAB).
• Keywords: TYROSINE KINASE INHIBITOR; THERAPIES; SCLC (small cell lung cancer); DNA-REPAIR; RECEPTOR; platinum-refractory; Cell Biology; amuvatinib; II TRIAL; MP-470; Science & Technology; Life Sciences & Biomedicine; etoposide; EXPRESSION; TOPOTECAN; CISPLATIN; RESISTANCE; C-KIT; Oncology
• Research Categories: Health Sciences, Pharmacy; Health Sciences, Oncology

Abstract

Background: Amuvatinib (MP-470) is a multi-targeted kinase inhibitor with potent activity against c-Kit, synergistic with DNA-damaging agents. We evaluated amuvatinib in combination with platinum-etoposide (EP) chemotherapy by objective response rate, survival, and tolerability in platinum-refractory small cell lung cancer (SCLC) patients. Methods: This study used a Simon 2-stage design requiring ≥3 centrally confirmed responses in the first 21 subjects. Subjects received EP with 300 mg amuvatinib orally three times daily in cycles of 21 days. A three-day amuvatinib run-in period before EP occurred in Cycle 1. Subjects received the same EP chemotherapy regimen given prior to progression/relapse. Results: Among 23 subjects treated, we observed four PRs (17.4%) per RECIST 1.1, only two of which were centrally confirmed (8.7%, response duration 119, 151 days). Three subjects (13%) had confirmed stable disease. c-Kit H-score was ≥100 in two subjects whose respective durations of disease control were 151 and 256 days. Conclusions: The addition of amuvatinib to EP chemotherapy in unselected, platinum-refractory SCLC did not meet the primary endpoint of ≥3 confirmed responses in stage 1. However, high c-Kit expression in two subjects with durable disease control suggests the potential for further study of amuvatinib in SCLC patients with high c-Kit expression.