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

Lauren Averett Byers, Leora Horn, Jitendra Ghandi, Goetz Kloecker, Taofeek Owonikoko, Saiama Naheed Waqar, Maciej Krzakowski, Robert J. Cardnell, Junya Fujimoto, Pietro Taverna, Mohammad Azab, David Ross Camidge

Research output: Contribution to journalArticlepeer-review

8 Scopus citations

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.

Original languageEnglish
Pages (from-to)81441-81454
Number of pages14
JournalOncotarget
Volume8
Issue number46
DOIs
StatePublished - 2017

Keywords

  • Amuvatinib
  • Etoposide
  • MP-470
  • Platinum-refractory
  • SCLC (small cell lung cancer)

Fingerprint

Dive into the research topics of 'A phase 2, open-label, multi-center study of amuvatinib in combination with platinum etoposide chemotherapy in platinumrefractory small cell lung cancer patients'. Together they form a unique fingerprint.

Cite this