Relay Therapeutics' Zovegalisib Shows Consistent Efficacy Across Breast Cancer Patient Subgroups in SABCS Analysis
Key Insights
Zovegalisib (search) combined with fulvestrant demonstrated consistent efficacy across different patient subgroups with PI3Kα (search)-mutated, HR+/HER2- metastatic breast cancer (search), achieving 10.3-month median progression-free survival in all patients.
The drug showed broad activity regardless of prior SERD exposure or ESR1 (search) mutation status, with objective response rates ranging from 39% to 60% across different patient populations.
Phase 3 ReDiscover-2 trial continues enrollment while the company advances dose escalation studies to inform future frontline metastatic treatment regimens.
Relay Therapeutics announced subset analysis results for zovegalisib (search) (RLY-2608), its investigational allosteric PI3Kα (search) inhibitor, demonstrating consistent efficacy across diverse patient populations with PI3Kα-mutated, HR+/HER2- metastatic breast cancer (search). The data, presented at the 2025 San Antonio Breast Cancer Symposium (SABCS), showed maintained therapeutic activity regardless of prior fulvestrant or SERD exposure, or ESR1 (search) mutation status.
Clinical Trial Results Show Broad Activity
The ReDiscover first-in-human study enrolled 118 patients into the zovegalisib (search) plus fulvestrant treatment arm as of the October 15, 2025 data cutoff. The efficacy analysis focused on 52 patients who received the 600mg twice daily fasted dose and did not have PTEN (search) or AKT (search) co-mutations, with a median follow-up of 20.2 months.
The median progression-free survival (PFS) reached 10.3 months for all patients, while the objective response rate (ORR) was 39% among 31 patients with measurable disease. Second-line patients demonstrated particularly strong outcomes with an 11.4-month median PFS and 47% ORR.
Consistent Efficacy Across Patient Subgroups
The subset analysis revealed robust activity across challenging patient populations. Among patients who received prior SERD therapy, median PFS was 11.4 months with an ORR of 44% (7/16 patients). Patients with detectable ESR1 (search) mutations at baseline achieved an 8.8-month median PFS and notably high 60% ORR (6/10 patients).
"Data presented today demonstrate the robust activity of zovegalisib (search) + fulvestrant across subgroups of patients whose baseline characteristics are known to affect outcomes, such as prior fulvestrant or SERD and ESR1 (search) mutation status," said Don Bergstrom, M.D., Ph.D., President of R&D at Relay Therapeutics.
Safety Profile Remains Manageable
The overall tolerability profile remained consistent with mutant-selective PI3Kα (search) inhibition, with treatment-related adverse events that were mostly low-grade, manageable and reversible. This safety profile supports the drug's potential for sustained treatment in the advanced breast cancer setting.
Development Program Advances
Relay Therapeutics continues enrollment in the Phase 3 ReDiscover-2 trial evaluating zovegalisib (search) plus fulvestrant in PI3Kα (search)-mutated, CDK4/6 (search) pre-treated, HR+/HER2- advanced breast cancer. The company is also advancing dose escalation in the Phase 1/2 ReDiscover trial, developing triplet combinations that could inform future frontline metastatic treatment approaches.
Precision Medicine Potential
Zovegalisib (search) represents the first known allosteric, pan-mutant and isoform-selective inhibitor of PI3Kα (search), the most frequently mutated kinase in all cancers and vascular malformations (search). The drug was designed using Relay's Dynamo platform to overcome limitations of traditional orthosteric PI3Kα inhibitors, which lack clinically meaningful selectivity between mutant and wild-type PI3Kα.
If approved, zovegalisib (search) has the potential to address nearly 500,000 patients in the United States, representing one of the largest patient populations for a precision medicine. The broad range of activity across patient subgroups highlights the importance of selectively targeting mutant PI3Kα (search) as the disease driver.
The company's development pipeline also includes ongoing enrollment in the Phase 1/2 ReInspire clinical trial evaluating zovegalisib (search) in PI3Kα (search)-driven vascular malformations (search), expanding the drug's potential therapeutic applications beyond oncology.