Relay Therapeutics Highlights Strong Efficacy and Tolerability for Zovegalisib at Phase 3 Dose in PI3Ka-Mutant Breast Cancer
Efficacy Remains Steady with 11.1 Month Median PFS at 400mg BID Fed Dose
Relay Therapeutics (NASDAQ: RLAY) announced encouraging data for its lead candidate, zovegalisib (RLY-2608), in combination with fulvestrant, at the 400mg twice daily (BID) fed dose. This regimen, now being highlighted at the ESMO Targeted Anticancer Therapies Congress 2026, mirrors the dosing for the ongoing pivotal Phase 3 ReDiscover-2 trial. Among 57 efficacy-evaluable, heavily pre-treated patients with PI3Ka-mutated, HR+/HER2- metastatic breast cancer—each previously treated with a CDK4/6 inhibitor—the median progression-free survival (PFS) reached 11.1 months. Notably, efficacy was consistent between those with kinase (11.2 months PFS) and non-kinase (11.0 months PFS) domain mutations.
Objective Response Rates and Global Patient Impact
The combination therapy recorded a 43% confirmed objective response rate (ORR) among patients with measurable disease. Notably, in second-line only patients, the ORR reached 52%. If approved, zovegalisib may address the needs of around 140,000 Americans with PI3Ka-mutated HR+/HER2- breast cancer and up to 170,000 with related vascular anomalies, further emphasizing its potential reach among large precision medicine patient cohorts.
| Efficacy Metric | 400mg BID Fed Dose | 600mg BID Fasted Dose |
|---|---|---|
| Median PFS (months) | 11.1 | Consistent |
| ORR (all measurable disease) | 43% | Similar |
| Kinase Mutations - Median PFS | 11.2 | Consistent |
| Non-Kinase Mutations - Median PFS | 11.0 | Consistent |
| Phase 3 ReDiscover-2 Status | Ongoing | N/A |
Tolerability Profile Consistent Across Doses
The safety and tolerability profile of zovegalisib at 400mg BID fed mirrors earlier findings with the 600mg BID fasted dose. Most treatment-related adverse events (TRAEs) were low grade, manageable, and reversible. Importantly, the majority of hyperglycemia events observed were Grade 1, with no severe (Grade 4-5) occurrences. Only four patients discontinued due to TRAEs, and most Grade 2/3 hyperglycemia incidences were in patients already pre-diabetic.
Pharmacokinetics Confirm Similar Exposure Between Doses
Pharmacokinetic analysis revealed that the 400mg BID fed regimen achieves drug concentrations comparable to the previously tested 600mg BID fasted dose. This similarity supports the use of the new feeding regimen in the pivotal Phase 3 ReDiscover-2 trial, reducing patient fasting burden without sacrificing efficacy or safety.
| Dose | Feeding State | Patient Number | Median Follow-Up (months) | Discontinuations (TRAEs) |
|---|---|---|---|---|
| 400mg BID | Fed | 60 | 12.0 | 4 |
| 600mg BID | Fasted | N/A | N/A | N/A |
FDA Breakthrough Therapy Designation Underscores Clinical Promise
Zovegalisib combined with fulvestrant has been granted FDA Breakthrough Therapy designation for the pivotal Phase 3 ReDiscover-2 trial population. The trial, currently enrolling globally, will directly compare zovegalisib plus fulvestrant with the combination of capivasertib and fulvestrant in patients whose cancer has progressed following CDK4/6 inhibitor therapy.
Key Takeaways: Competitive Differentiation and Patient Impact
Relay Therapeutics’ strategy leverages zovegalisib’s pan-mutant, isoform-selective PI3Ka inhibition—a targeted approach designed to avoid the toxicity and dose limitations tied to existing PI3Ka inhibitors. With compelling efficacy and a manageable safety profile, this latest data reinforces confidence heading into a make-or-break Phase 3 readout. With a large U.S. patient population and early regulatory recognition, zovegalisib could redefine treatment standards for advanced HR+/HER2- breast cancer if Phase 3 results are similarly positive.
The data presentation is available at Relay Therapeutics' official website in the “Publications/Presentations” section.
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