Trials / Recruiting
RecruitingNCT06395519
A Study of PARG Inhibitor ETX-19477 in Patients With Advanced Solid Malignancies
- Status
- Recruiting
- Phase
- Phase 1 / Phase 2
- Study type
- Interventional
- Enrollment
- 120 (estimated)
- Sponsor
- 858 Therapeutics, Inc. · Industry
- Sex
- All
- Age
- 18 Years
- Healthy volunteers
- Not accepted
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.
Detailed 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 double-strand breaks (DSBs) and reduced kinetics of break repair. In addition, under conditions of replication stress in cancer cells, PARG depletion or inhibition has been shown to inhibit proliferation and arrest cells in the S or G2 phase of the cell cycle and/or induce apoptosis alone or in combination with DNA damaging agents or replication stress inducers. The replication stress response represents a cancer-specific vulnerability, which can be targeted by PARG small molecule inhibition.
Conditions
- Advanced or Metastatic Solid Tumors
- Breast Cancer
- Ovarian Cancer
- Prostate Cancer
- Epithelial Ovarian Cancer
- BRCA2 Mutation
- ER+ Breast Cancer
- Castrate Resistant Prostate Cancer
- BRCA1 Mutation
- BRCA Mutation
- Endometrial Cancer
- Colorectal Cancer
- Gastric Cancer
Interventions
| Type | Name | Description |
|---|---|---|
| DRUG | ETX-19477 | Oral medication taken daily |
Timeline
- Start date
- 2024-05-13
- Primary completion
- 2026-12-01
- Completion
- 2026-12-01
- First posted
- 2024-05-02
- Last updated
- 2026-03-27
Locations
14 sites across 1 country: United States
Regulatory
- FDA-regulated drug study
Source: ClinicalTrials.gov record NCT06395519. Inclusion in this directory is not an endorsement.