A Study of PARG Inhibitor ETX-19477 in Patients With Advanced Solid Malignancies
858 Therapeutics, Inc.
Summary
This is a two-part, open-label, multicenter, dose escalation and dose expansion study designed to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PDx), and anti- tumor activity of ETX-19477, a novel reversible small molecule inhibitor of PARG.
Description
A hallmark of many cancer cells is replication stress, which is characterized by the slowing or stalling of replication forks during the DNA replication process, leading to the accumulation of damaged DNA. The cellular response to replication stress is the activation of cell-cycle checkpoints and the DNA damage response (DDR) pathway to arrest the cell cycle and promote repair of the damaged DNA. Poly (ADP) ribose glycohydrolase (PARG) plays a critical role in DDR with genetic depletion or inhibition by reference compounds resulting in increased numbers of single-strand breaks (SSBs) and doub…
Eligibility
- Age range
- 18+ years
- Sex
- All
- Healthy volunteers
- No
Inclusion Criteria: * Males and females of age ≥ 18 years at the time of signing the informed consent document. * Histologically or cytologically confirmed advanced (incurable recurrent, unresectable, or metastatic) solid cancer, excluding primary central nervous system (CNS) tumors. * Any solid tumor malignancy, excluding primary CNS tumors, with progression on or after or intolerance to most recent systemic therapy. Preferential enrollment consideration will be made for patients with known BRCA2 mutations resulting in loss of function. * Measurable disease per RECIST v1.1. * ECOG performanc…
Interventions
- DrugETX-19477
Oral medication taken daily
Locations (14)
- Mayo ClinicPhoenix, Arizona
- Yale University, Yale Cancer CenterNew Haven, Connecticut
- Mayo ClinicJacksonville, Florida
- University of Chicago Medical CenterChicago, Illinois
- Massachusetts General HospitalBoston, Massachusetts
- Mayo ClinicRochester, Minnesota