A phase 2 multicenter study of tivantinib (ARQ 197) monotherapy in patients with relapsed or refractory germ cell tumors
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Background Tivantinib is a selective, small-molecule inhibitor of the MET receptor tyrosine kinase. Preclinical and phase 1 data suggested a possible role for MET in the pathophysiology of germ cell tumors (GCTs) and a potential clinical benefit from tivantinib in patients with these tumors. Methods Men (≥16 years) with relapsed or refractory, histologically confirmed, non-central nervous system GCTs received oral tivantinib 360 mg twice daily in 28-day cycles until progressive disease or unacceptable toxicity. The primary endpoint was objective response rate in the first 4 cycles, with study termination for <2 responses among the first 21 patients. Secondary endpoints included 12-week progression-free survival (PFS), overall survival (OS), and safety. Results Twenty-seven patients were enrolled in 9 months (median age, 32 years). Most patients had tumors with nonseminoma histology (n = 25), and primary tumor sites were testis (n = 24) and mediastinum (n = 3). Among 25 evaluable patients, no objective responses were observed; accrual was halted when the 21st patient became evaluable. Best response was stable disease (n = 5). Median PFS was 1 month, the 12-week PFS rate was 21 %, and median OS was 6 months. Grade 3 or 4 adverse events considered related to study drug included grade 3 pneumonia and grade 3 syncope (n = 1, each). Conclusions Tivantinib was well tolerated but did not demonstrate single-agent activity in patients with relapsed/refractory GCTs. Rapid accrual to this phase 2 trial was achieved in this rare patient population through multicenter collaboration.
KeywordsARQ 197 Germ cell tumor MET receptor tyrosine kinase MET inhibitor Tivantinib Relapsed
Financial support for medical editorial assistance was provided by Daiichi Sankyo, Inc., a member of the Daiichi Sankyo Group, and ArQule, Inc. We thank Bret A. Wing, PhD, ProEd Communications, Inc., for his medical editorial assistance with this manuscript.
Conflicts of interest
DRF, LHE, YL, JKJ, DJV, AF, and JH have no disclosures of interest.
DIQ is an advisory board member for and has received honoraria from Pfizer, Bayer, Dendreon, Novartis, Aveo, Prometheus, Teva, and Medivation.
A-BH and HZ are employees of Daiichi Sankyo, Inc.
RJM has received research funding from ArQule, Inc.
This study was approved by the institutional review boards of the participating institutions and was conducted according to institutional and federal guidelines. Written informed consent was obtained from all patients before study participation.
Financial support for medical editorial assistance was provided by Daiichi Sankyo, Inc., a member of the Daiichi Sankyo Group, and ArQule, Inc.
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