Relay Therapeutics (RLAY) Study Update summary

Key study results

• RLY-2608 plus fulvestrant achieved a median progression-free survival (PFS) of 9.2 months in heavily pretreated, HR-positive, HER2-negative, PIK3CA-mutated breast cancer patients, outperforming the 5.5–5.6 months seen with capivasertib and alpelisib in similar populations.

• Objective response rate (ORR) was 33% and clinical benefit rate (CBR) was 57%, with tumor reduction observed in 73% of patients and robust ctDNA clearance across mutation subtypes.

• In patients with kinase domain mutations, mPFS reached 10.3 months and ORR was 53%.

• 97% of patients showed a decline in PIK3CA ctDNA, with 54% achieving complete clearance by cycle 2 day 1.

• Efficacy and safety were consistent across kinase and non-kinase domain PIK3CA mutations, supporting broad inclusion in future pivotal trials.

Safety and tolerability profile

• Only 25% of patients at the recommended Phase II dose experienced Grade 3 treatment-related adverse events (TRAEs), with no Grade 4/5 events and a single Grade 3 hyperglycemia case, indicating a favorable safety profile.

• Most common TRAEs included hyperglycemia (47% all grades, 1.6% grade 3), nausea, and fatigue, with limited impact on glucose homeostasis.

• Only two patients discontinued due to TRAEs; 95% median dose intensity was maintained at RP2D.

• Dose intensity was maintained at 95%, with low rates of discontinuation and dose modification compared to other PI3K inhibitors.

• Tolerability profile compares favorably to approved PI3Ka inhibitors, with lower rates of severe hyperglycemia and discontinuations.

Study design and patient population

• The REDISCOVER trial enrolled over 200 patients across multiple arms, focusing on a heavily pretreated population, with half having received two or more prior therapies and over half previously treated with fulvestrant or a novel SERD.

• Dose escalation and expansion included 118 patients for safety and 52 patients at 600mg BID for efficacy, excluding PTEN/AKT co-mutations.

• Median patient age was 59, with 59% having visceral metastases and 45% receiving two or more prior lines of therapy.

• Nearly two-thirds had visceral metastases, and over a third had high BMI and/or elevated baseline HbA1c, reflecting a real-world Western patient population.

• No prior PI3K pathway inhibitor treatment was allowed for inclusion in the REDISCOVER trial.