Oncotarget

Clinical Research Papers:

A phase 2, open-label, multi-center study of amuvatinib in combination with platinum etoposide chemotherapy in platinum-refractory 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 and David Ross Camidge

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Oncotarget. 2017; 8:81441-81454. https://doi.org/10.18632/oncotarget.19888

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Abstract

Lauren Averett Byers1, Leora Horn2, Jitendra Ghandi3, Goetz Kloecker4, Taofeek Owonikoko5, Saiama Naheed Waqar6, Maciej Krzakowski7, Robert J. Cardnell1, Junya Fujimoto1, Pietro Taverna8, Mohammad Azab8 and David Ross Camidge9

1University of Texas, M.D. Anderson Cancer Center, Houston, TX, USA

2Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, TN, USA

3Associates in Oncology and Hematology, Chattanooga, TN, USA

4James Graham Brown Cancer Center, University of Louisville, Louisville, KY, USA

5Winship Cancer Institute, Emory University, Atlanta, GA, USA

6Siteman Cancer Center, Washington University School of Medicine, St Louis, MO, USA

7Centrum Onkologii-Instytut Im. M. Skłodowskiej-Curie w Warszawie, Warszawa, Poland

8Astex Pharmaceuticals, Inc. Pleasanton, CA, USA

9Anschutz Cancer Pavilion, University of Colorado Cancer Center, Aurora, CO, USA

Correspondence to:

Lauren Averett Byers, email: [email protected]

Keywords: amuvatinib, MP-470, platinum-refractory, etoposide, SCLC (small cell lung cancer)

Received: June 08, 2017    Accepted: July 09, 2017    Published: August 03, 2017

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.


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