Relay Wins Early on Breast Cancer, Arranges Crucial Trial Against Truqap from AstraZeneca

Relay Therapeutics released interim Phase I/II data showing that RLY-2608, its investigational PI3Kα inhibitor, demonstrated “clinically meaningful” progression-free survival (PFS) in patients with specific molecular subtypes of metastatic breast cancer.
The study, called ReDiscover, enrolled patients with locally advanced or metastatic breast cancer that was PI3Kα-mutated, ER-positive, and HER2-negative. RLY-2608 was administered at its recommended Phase II dose of 600 mg twice daily and given in four treatment arms: as a monotherapy for advanced breast cancer, with AstraZeneca’s hormone therapy Truqap (fulvestrant), with fulvestrant and ribociclib, or with fulvestrant and atirmociclib. Both ribociclib and atirmociclib are CDK4/6 inhibitors.

At this dose, RLY-2608 provided a median PFS of 9.2 months, regardless of mutation. In patients with a kinase mutation, PFS was measured at 10.3 months. The clinical benefit rate, calculated as the percentage of evaluable patients who had a complete response, partial response, or stable disease at 24 weeks, was 57%.
Additionally, 30 patients had assessable disease at the time of the analysis, with 10 patients meeting the criteria for partial response, resulting in an overall response rate (ORR) of 33%. Among the 15 patients with measurable disease and kinase mutations, the ORR was 53%.
According to Relay, RLY-2608 demonstrated a “meaningfully differentiated tolerability profile.” The side effects were mostly low-grade and, in most cases, manageable and reversible. Two patients discontinued the study due to toxicity, and only 25% of adverse events were considered Grade 3.
In a statement, Don Bergstrom, President of R&D at Relay, noted that the data indicate RLY-2608 has the potential to provide patients with benefits that other non-selective medications could not offer, with significantly less toxicity. Based on these early results, Relay plans to “move fast” to meet with regulators and design the pivotal trial.
Relay anticipates initial safety data on RLY-2608, ribociclib, and fulvestrant, to be released later this year. The atirmociclib triplet cohort with RLY-2608 is expected to begin by the end of this year.

RLY-2608 is a mutant-selective inhibitor of PI3Kα, which, in its normal state, plays a crucial role in many important cellular functions. By analyzing human cancer databases, Relay found that PI3Kα is “the most commonly amplified kinase in all cancers,” constituting approximately 14% of oncogenic variants in solid tumors.
Truqap, developed by AstraZeneca, targets AKT within the PIK3CA pathway. If approved, RLY-2608 has the potential to treat more than 300,000 patients annually in the United States alone, according to Relay’s estimates.

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