A First-in-Human, Phase I Clinical Trial of Mitochondrial-Targeted Hsp90 Inhibitor, Gamitrinib, in Advanced and Metastatic Prostate Cancer
Abstract
Research supported by the present application is designed to conduct a first-in-human, phase I clinical trial of the novel, mitochondrial-targeted small molecule Hsp90 inhibitor, Gamitrinib in patients with advanced cancer, including advanced, castration-resistant and metastatic prostate cancer. The clinical trial will be conducted at the Phase I Developmental Therapeutics Program of Fox Chase Cancer Center under the leadership of Anthony Olszanski, M.D., Director of the Program. These studies will be complemented by analysis of pharmacodynamics and biochemical characterization of target engagement of Gamitrinib therapy in an expansion cohort at maximal tolerated dose (MTD) inpatients with advanced prostate cancer. Accomplishments obtained during the last reporting period have significantly advanced the fulfillment of the stated specific aims. Accordingly, a new formulation development of Gamitrinib has been successfully completed to include an innovative step of microfluidization designed to reduce particle size of the nanosuspension, and thus enable terminal sterilization for use in humans. Validated methods and three-month stability testing have also been established to support the large-scale manufacturing of GMP-grade Gamitrinib for clinical use, and protocols for drug substance identification and validation have been finalized. An Institutional Review Board (IRB)approval of the Gamitrinib clinical trial has been secured as well as Department of Defense (DoD) HRPO concurrence on human subject designation. Altogether, the program is on-track for submission of full Investigational New Drug (IND)application to the US Food and Drug Administration by December 2019 with patient enrollment scheduled to begin by March 2020. Although this is a single-site clinical trial, we expect a rapid accrual rate consistent with the timeline approved in the original Statement of Work.
Document Details
- Document Type
- Technical Report
- Publication Date
- Dec 01, 2021
- Accession Number
- AD1156560
Entities
People
- Dario C Altieri
Organizations
- Wistar Institute