FDA Fast-Tracks PARG Inhibitor for mBRCA Platinum-Resistant Ovarian Cancer

The investigational small molecule inhibitor ETX-19477 has earned fast track designation from the FDA, accelerating its clinical development for treatment of adult patients with BRCA-mutated, platinum-resistant, high-grade serous ovarian cancer.¹

The FDA grants fast track status to agents that promise to address serious conditions with unmet needs.² The designation will support ETX-19477’s development program, including the phase 1/2 ERADIC8 trial (NCT06395519), with benefits such as increased communications with the FDA and possible eligibility for accelerated approval, priority review, and rolling review if criteria are met. For this patient population who face limited treatment options, this development is a promising signal for a potential accelerated path to market, which would enable sooner access to a new alternative.

“Patients with platinum-resistant ovarian cancer have a poor prognosis, and treatment options remain extremely limited, highlighting a substantial unmet need for new therapies,” said Jeffrey Stafford, PhD, CEO of 858 Therapeutics, in a news release.¹ “We are pleased that the FDA has granted [f]ast [t]rack designation to ETX-19477 and we are committed to working closely with the FDA to accelerate its development. This designation was based on preclinical data and emerging clinical data from our ongoing [p]hase 1/2 trial of ETX-19477, including antitumor activity at tolerable doses.”

About ETX-19477 and Mechanistic Rationale

ETX-19477 is a potent, selective inhibitor of poly(ADP-ribose) glycohydrolase (PARG), an enzyme that plays a role in the DNA damage response.^3,4 Upon PARG inhibition, the agent is intended to inhibit cancer cell proliferation and induce selective apoptosis in tumors with underlying replication fork defects, including BRCA-mutated tumors.

In preclinical studies, the agent demonstrated favorable pharmacokinetics and oral bioavailability, tolerability, and dose-dependent antitumor activity in vivo in breast and ovarian xenograft models, justifying advancement into the clinical setting.

About the ERADIC8 Trial

The ongoing multicenter, open-label, dose-escalation and -expansion ERADIC8 study has set out to explore the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary antitumor activity of orally administered, once-daily ETX-19477 monotherapy in advanced solid malignancies.⁵

The primary end point of the study is safety and tolerability, as indicated by the frequency of dose-limiting toxicities, frequency and severity of adverse events (AEs), and serious AEs within a 6-month time frame. Secondary measures of efficacy include objective response rate, duration of response, and disease control rate per RECIST v1.1 criteria.

The US-based study is recruiting up to an estimated 120 adult patients with solid tumor malignancies including breast, ovarian, prostate, epithelial, endometrial, colorectal, and gastric cancers, with preferential enrollment for patients with known BRCA2 mutations. For enrollment, patients must have progressed on or after or have intolerance to their most recent systemic therapy and must not have any primary central nervous system tumors.

The study is projected to conclude by the end of 2026.

REFERENCES

1. 858 Therapeutics announces FDA fast track designation for PARG inhibitor ETX-19477 for the treatment of patients with BRCA-mutated, platinum-resistant ovarian cancer. News release. 858 Therapeutics. January 8, 2026. Accessed January 8, 2026. https://tinyurl.com/ye2dtzd2

2. Fast track. US Food & Drug Administration. Updated August 13, 2024. Accessed January 8, 2026. https://tinyurl.com/ms2695jn

3. Hu Y, Meng Y, Zhuang Z, et al. Prospects for PARG inhibitors in cancer therapy. J Mol Cell Biol. 2025;16(11):mjae050. doi:10.1093/jmcb/mjae050

4. Holleran JP, Rodems TS, Sharma S, et al. Abstract 2083: Discovery of ETX-19477, a novel and selective PARG inhibitor with high potency against tumors with underlying replication stress. Cancer Res. 2024;84(6_Supplement):2083-2083. doi:10.1158/1538-7445.am2024-2083

5. A study of PARG inhibitor ETX-19477 in patients with advanced solid malignancies (ERADIC8). ClinicalTrials.gov. Updated August 5, 2025. Accessed January 8, 2026. https://www.clinicaltrials.gov/study/NCT06395519