Relay Scores Early Breast Cancer Win, Plans Pivotal Trial Against AstraZeneca’s Truqap
On Monday, Relay Therapeutics announced interim Phase I/II results for its innovative PI3Kα inhibitor, RLY-2608, demonstrating significant progression-free survival benefits in patients with heavily treated breast cancer cases.
The clinical study, named ReDiscover, targeted individuals with PI3Kα mutations who also had hormone receptor-positive and HER2-negative locally advanced or metastatic breast cancer. Participants received RLY-2608 at a recommended Phase II dosage of 600 mg, taken twice daily, through four distinct treatment arms: alone, in combination with AstraZeneca’s hormone therapy Truqap (fulvestrant), alongside fulvestrant plus ribociclib, or with fulvestrant and atirmociclib. Both ribociclib and atirmociclib serve as CDK4/6 inhibitors.
The findings revealed that RLY-2608 produced a median progression-free survival (PFS) of 9.2 months across all patients. Notably, individuals with kinase mutations experienced a slightly extended PFS of 10.3 months. The clinical benefit rate—calculated as the proportion of evaluable patients who achieved either a complete or partial response or stable disease after 24 weeks—was reported at 57%.
Among the 30 patients assessed for measurable disease at the time of analysis, 10 recorded a partial response, yielding an objective response rate (ORR) of 33%. Furthermore, in the subgroup of 15 patients with measurable disease and kinase mutations, the ORR increased to 53%.
According to Relay, RLY-2608 displayed a “distinctly favorable tolerability profile” in the ReDiscover study. Adverse effects were mainly low-grade and could be easily managed. Only two patients withdrew due to treatment-related side effects, while just 25% of all reported toxicities reached grade 3 severity.
Don Bergstrom, Relay’s president of R&D, commented on the findings, indicating that RLY-2608 “may provide a level of benefit to patients previously unattainable with existing non-selective treatments, while also presenting significantly lower toxicity.” Encouraged by this promising data, Relay plans to expedite discussions with regulatory bodies to outline a pivotal trial design, anticipating commencement in the next year.
The company aims to present initial safety results for RLY-2608 in combination with ribociclib and fulvestrant by the fourth quarter of 2024, with a dose-expansion cohort expected in the first half of 2025. Meanwhile, the triplet cohort with atirmociclib is slated to launch by year-end.
RLY-2608 specifically targets mutant PI3Kα, a critical factor in multiple cellular operations under normal physiological conditions. Relay highlights that PI3Kα is “the most commonly mutated kinase across all cancers,” linked to 14% of oncogenic mutations in solid tumors.
In contrast, AstraZeneca’s Truqap focuses on AKT, another protein within the PIK3CA signaling pathway.
If authorized for use, RLY-2608 could potentially benefit over 300,000 patients annually in the United States, as projected by Relay Therapeutics.