Summary
Background Trebananib is an anti-angiogenic peptibody under investigation in patients with advanced cancer. This study evaluated the pharmacokinetic (PK) drug-drug interaction of paclitaxel and trebananib. Patients and methods Patients with advanced solid tumors received weekly 80 mg/m2 intravenous (IV) paclitaxel (3 weeks on/1 week off) with weekly 15 mg/kg IV trebananib starting at Week 2. Blood samples for PK analysis were collected at Week 1 (paclitaxel alone), Week 6 (paclitaxel and trebananib), and Week 8 (trebananib alone). An absence of interaction was to be concluded if the 90 % confidence intervals (CI) for the differences in paclitaxel exposure fell within the 0.80–1.25 interval. Results The primary study was conducted between 7/2012 and 10/2013. Thirty-five patients were enrolled and 34 received both treatments. Most patients were white (91 %) and female (59 %); mean age was 61 years. The most common tumor types were ovarian (32 %) and bladder (27 %), 71 % of patients had stage IV disease, and all had Eastern Cooperative Oncology Group (ECOG) scores of 0 or 1. PK parameter analysis was done on patients with evaluable PK data at both assessments (with and without concomitant therapy; n = 28). The geometric least squares mean (GLSM) ratio (90 % CI) of paclitaxel AUCinf with and without trebananib was 1.17 (1.10, 1.25). The GLSM ratio (90 % CI) of trebananib AUCtau,ss with and without paclitaxel was 0.92 (0.87, 0.97). The most common adverse events were fatigue, local edema, peripheral edema, and nausea. Conclusions This study showed no evidence of clinically meaningful PK interaction between paclitaxel and trebananib.
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Acknowledgments
The authors would like to thank the patients and their families, as well as the study staff, for their participation; and Zhandong Don Zhong (Amgen Inc.) for performing the anti-trebananib antibody analysis. Wanda Krall, PhD, whose work was funded by Amgen Inc., and Beate Quednau, PhD, of Amgen, assisted in the preparation of this manuscript.
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This study was funded by Amgen Inc.
Conflict of interest
Jennifer Diamond, Neeraj Agarwal, Daniel Bowles, and Elaine Lam report no potential conflict of interest. Sunil Sharma reports research funding from Amgen and holds stock in Beta Cat Pharmaceuticals, Salarius Pharmaceuticals, and ConverGene. Theresa Werner reports research support to the institution from Abbvie, Amgen, Bayer, GlaxoSmithKline, Novartis, Roche-Genentech, and Pfizer. Benjamin Wu, Erik Rasmussen, Felipe Soto, Greg Friberg are employees of and stock holders in Amgen Inc. Erick Gamelin and Yu-Nien Sun were employees of Amgen Inc. at the time the research was conducted and continue to be stock holders in Amgen Inc.
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All procedures performed in this study involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.
This article does not contain any studies with animals performed by any of the authors.
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All participants gave their informed consent in writing prior to inclusion in the study.
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Jennifer R. Diamond and Benjamin Wu contributed equally.
Erick Gamelin and Yu-Nien Sun: Affiliation at the time the research was conducted
Amgen Inc., Thousand Oaks, CA
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Diamond, J.R., Wu, B., Agarwal, N. et al. Pharmacokinetic drug-drug interaction study of the angiopoietin-1/angiopoietin-2-inhibiting peptibody trebananib (AMG 386) and paclitaxel in patients with advanced solid tumors. Invest New Drugs 33, 691–699 (2015). https://doi.org/10.1007/s10637-015-0236-4
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DOI: https://doi.org/10.1007/s10637-015-0236-4