Relay Therapeutics' Zovegalisib 400mg BID Fed Shows 11.1-Month PFS, Gains Breakthrough Status
Relay Therapeutics reported Phase 1/2 data showing that 400mg twice-daily fed zovegalisib plus fulvestrant achieved a median progression-free survival of 11.1 months in 57 PI3Kα-mutated, HR+/HER2- metastatic breast cancer patients. Efficacy was consistent across kinase (11.2 months) and non-kinase (11.0 months) mutations and the regimen holds FDA Breakthrough Therapy designation.
1. Phase 1/2 ReDiscover Fed Dose Data
The Phase 1/2 ReDiscover trial evaluated zovegalisib at 400mg twice daily with food in 60 patients with PI3Kα-mutated, HR+/HER2- metastatic breast cancer who had received prior CDK4/6 inhibitor and endocrine therapy. As of the January 13, 2026 cut-off, 57 patients were efficacy-evaluable and achieved a median progression-free survival of 11.1 months with a median follow-up of 12.0 months.
2. Efficacy Across Mutation Subtypes
Analysis showed similar PFS in patients with kinase domain mutations (11.2 months, n=33) and non-kinase domain mutations (11.0 months, n=24). Among 35 patients with measurable disease, the confirmed objective response rate was 43% overall and 52% in second-line only patients (11 of 21).
3. Pharmacokinetics and Safety Profile
Pharmacokinetic data indicate the 400mg BID fed regimen achieves exposures comparable to the 600mg BID fasted dose, maintaining mean concentrations near IC90 and above IC80 throughout dosing. The safety profile was consistent with prior data, with mostly low-grade, reversible adverse events; hyperglycemia events were primarily Grade 1, no Grade 4–5 events, and only four patients discontinued due to treatment-related adverse events.
4. Phase 3 ReDiscover-2 Trial and Breakthrough Designation
Based on these results, Relay advanced the 400mg BID fed regimen into the ongoing Phase 3 ReDiscover-2 trial, which began mid-2025 and is comparing zovegalisib plus fulvestrant versus capivasertib plus fulvestrant in patients who progressed on CDK4/6 therapy. Zovegalisib has received FDA Breakthrough Therapy designation for this trial population.