Phase i trial of the HSP90 inhibitor PF-04929113 (SNX5422) in adult patients with recurrent, refractory hematologic malignancies

Nishitha Reddy, Peter M. Voorhees, Brett E. Houk, Nicoletta Brega, James M. Hinson, Anand Jillela

Research output: Contribution to journalArticle

19 Scopus citations

Abstract

Background: Heat shock protein (HSP)90 regulates the function of proteins responsible for cell growth and survival, is overexpressed in many cancers and is an attractive therapeutic target. We undertook a phase 1 trial of PF-04929113 (SNX-5422), a novel oral HSP90 inhibitor, to estimate the maximum tolerated dose and describe the pharmacokinetic and toxicity profiles. Patients and Methods: Patients with relapsed, refractory, hematologic malignancies and adequate organ function were eligible. PF-04929113 was administered orally every other day for 21 days of a 28-day cycle. Twenty-five patients were treated, with dose escalation ranging from 5.32 mg/m2 to 74 mg/m2 using a 3 plus 3 trial design. Results: All 25 patients enrolled were evaluable for toxicity. Most common toxicities included prolonged QTc interval, diarrhea, pruritus, thrombocytopenia, fatigue, and nausea. Grade 3/4 treatment-related adverse events were experienced by 7/25 patients (28%); thrombocytopenia was the most common (n = 3 grade 3; n = 2 grade 4). Partial response was experienced by a patient with transformed lymphoma, and prolonged stabilization of disease was observed in a patient with multiple myeloma. Conclusion: Alternate-day oral dosing of PF-04929113 at 74 mg/m2 for 21/28 days was generally well tolerated with reversible toxicity. The responses observed in myeloma and lymphoma patients are encouraging.

Original languageEnglish (US)
Pages (from-to)385-391
Number of pages7
JournalClinical Lymphoma, Myeloma and Leukemia
Volume13
Issue number4
DOIs
StatePublished - Aug 1 2013

Keywords

  • Clinical trial
  • Heat shock protein
  • Pharmacokinetics

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research

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