A phase 1 study of IPI-504 (retaspimycin hydrochloride) in patients with relapsed or relapsed and refractory multiple myeloma

Abstract

A phase 1 study of IPI-504 (retaspimycin hydrochloride) administered intravenously twice weekly for 2 weeks at 22.5, 45, 90, 150, 225, 300 or 400 mg/m² followed by 10 days off-treatment was conducted to determine the safety and maximum tolerated dose (MTD) of IPI-504 in patients with relapsed or relapsed/refractory multiple myeloma (MM). Anti-tumor activity and pharmacokinetics were also evaluated. Eighteen patients (mean age 60.5 years; median 9 prior therapies) were enrolled. No dose-limiting toxicities (DLTs) were reported for IPI-504 doses up to 400 mg/m². The most common treatment-related adverse event was grade 1 infusion site pain (four patients). All other treatment-related events were assessed as grade 1 or 2 in severity. The area under the curve (AUC) increased with increasing dose, and the mean half-life was approximately 2–4 h for IPI-504 and its metabolites. Four patients had stable disease, demonstrating modest single-agent activity in relapsed or relapsed/refractory MM.

Keywords::

• Multiple myeloma
• HSP90
• IPI-504
• phase 1
• relapsed/refractory

Acknowledgements

We thank all of the patients who participated in the study, their families and all the physicians and study staff involved.

David Siegel, Sundar Jagannath, David H. Vesole, Ivan Borello, Amitabha Mazumder, Constantine Mitsiades, Kenneth C. Anderson and Paul Richardson received research funding from Infinity Pharmaceuticals, Inc. to support the conduct of this trial.

Potential conflict of interest:

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