Open Access Research article

A first in human, safety, pharmacokinetics, and clinical activity phase I study of once weekly administration of the Hsp90 inhibitor ganetespib (STA-9090) in patients with solid malignancies

Jonathan W Goldman1*, Robert N Raju2, Gregory A Gordon2, Iman El-Hariry3, Florentina Teofilivici3, Vojo M Vukovic3, Robert Bradley3, Michael D Karol3, Yu Chen3, Wei Guo3, Takayo Inoue3 and Lee S Rosen1

Author Affiliations

1 UCLA Medical Center, Suite 600, 2020 Santa Monica Blvd, Santa Monica, CA 90404, USA

2 Kettering Health Network Innovation Center, 3535 Southern Blvd, Kettering, OH 45429, USA

3 Synta Pharmaceuticals Corp., 125 Hartwell Ave, Lexington, MA 02421, USA

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BMC Cancer 2013, 13:152  doi:10.1186/1471-2407-13-152

Published: 25 March 2013



This phase I study investigated the maximum tolerated dose (MTD), safety, pharmacokinetics and antitumor activity of ganetespib in patients with solid malignancies.


Patients were enrolled in cohorts of escalating ganetespib doses, given as 1 hour IV infusion, once weekly for 3 weeks, followed by a 1-week rest until disease progression or unacceptable toxicity. Endpoints included safety, pharmacokinetic and pharmacodynamic parameters and preliminary clinical activity.


Fifty-three patients were treated at doses escalating from 7 to 259 mg/m2. The most common adverse events were Grade 1 and 2 diarrhea, fatigue, nausea or vomiting. Dose-limiting toxicities (DLT) observed were: one Grade 3 amylase elevation (150 mg/m2), one Grade 3 diarrhea and one Grade 3 and one Grade 4 asthenia (259 mg/m2). The MTD was 216 mg/m2 and the recommended phase 2 dose was established at 200 mg/m2 given IV at Days 1, 8, and 15 every 4 weeks. There was a linear relationship between dose and exposure. Plasma HSP70 protein levels remained elevated for over a week post treatment. Disease control rate (objective response and stable disease at ≥ 16 weeks) was 24.4%.


Ganetespib is well tolerated as a weekly infusion for 3 of every 4 weeks cycle. The recommended phase II dose is 200 mg/m2, and is associated with an acceptable tolerability profile.

Trial registration


Ganetespib; Hsp90 inhibitor; Pharmacokinetics; Phase I study; Solid tumors