Phase I trial of the HSP-90 inhibitor PU-H71.

Abstract

2537 Background: PU-H71 (PU) is an HSP-90 inhibitor that can be labeled with 124I without altering its biochemical properties. Intratumoral drug concentration can be calculated based on 124I-PU-H71 (*PU) PET imaging, leading to a surrogate marker of intratumoral pharmacokinetics. Methods: Patients (pts) with previously treated solid tumors, lymphoma and myeloproliferative neoplasms (MPN) on ruxolitinib were eligible. PU was given days 1, 4, 8, 11 each 21 days at escalating dose levels using a Continuous Reassessment Method (CRM). The primary objective was determination of the MTD. Secondary objectives included plasma and intratumoral PKs measured by pre- and on-treatment core needle biopsies (CNB) and by *PU PET imaging. Results: To date, 40 pts have received PU at doses from 10-400mg/m2. 37 are currently evaluable for DLT, and the last 3 pts needed (per CRM) are being enrolled. Five pts experienced DLTs: 1 (of 2) at 400 mg/m2 - grade 3 mucositis; 4 (of 7) at 350 mg/m2 – 1 pt grade 3 AST and ALT, 1 pt gra...