San Diego-based biotech 858 Therapeutics reported a 57% objective response rate for ETX-19477 in a small Phase II-eligible subset of patients with BRCA-mutated platinum-resistant ovarian cancer and HR+/HER2- breast cancer, marking the first clinical proof-of-concept for PARG inhibition in either tumor type.
The data come from ERADIC8 (NCT06395519), a first-in-human Phase I/II dose-escalation and expansion study enrolling patients with advanced solid tumors at multiple US sites. The ASCO abstract covers 45 patients; a poster presentation at the 2026 ASCO Annual Meeting on May 30 will feature an expanded dataset of 53 patients. The 57% ORR was observed in a Phase II-eligible subset of seven patients meeting stricter prior-therapy limits — no more than five prior lines for ovarian cancer and no more than two for breast cancer. Durable RECIST responses were observed in both tumor types. ETX-19477 was generally well tolerated, with low rates of hematologic toxicity; granular adverse event data were not disclosed. The company also reported a robust pharmacokinetic-pharmacodynamic relationship established during dose escalation, which it said supports continued monotherapy development and future combination strategies.
ETX-19477 inhibits PARG, the enzyme that removes poly(ADP-ribose) chains from proteins during the DNA damage response — a mechanism distinct from PARP inhibition, which blocks PAR synthesis rather than degradation. The clinical benchmark in BRCA-mutated ovarian cancer remains AstraZeneca's Lynparza (olaparib) and other approved PARP inhibitors, though cross-trial comparisons are limited given differences in patient selection, prior treatment history, and trial design. Ideaya Biosciences has also advanced a PARG inhibitor program into early clinical testing, though no comparative efficacy data are publicly available. With Phase II monotherapy expansion cohorts actively enrolling, 858 Therapeutics' next milestone will be a more powered readout in BRCA-mutated ovarian and breast cancer populations.
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