Relay Therapeutics, in collaboration with Pfizer, is set to evaluate a novel triplet therapy combining RLY-2608, atirmociclib, and fulvestrant for patients with PI3Kα-mutated, HR+/HER2- metastatic breast cancer. The clinical trial, expected to commence by the end of 2024, aims to improve treatment outcomes by selectively targeting mutant PI3Kα while minimizing off-target toxicities.
Rationale for the Triplet Combination
The combination therapy leverages the selectivity of RLY-2608, Relay Therapeutics' mutant selective PI3Kα inhibitor, and atirmociclib, Pfizer’s selective-CDK4 inhibitor. This approach is designed to avoid the toxicities associated with non-selective agents that inhibit CDK6 and wild-type PI3Kα. According to Don Bergstrom, M.D., Ph.D., President of R&D at Relay Therapeutics, this strategic combination aims to create a next-generation therapy with an improved safety profile.
About RLY-2608
RLY-2608 is designed as an allosteric, pan-mutant, and isoform-selective PI3Kα inhibitor. PI3Kα is frequently mutated in various cancers, with oncogenic mutations detected in approximately 14% of patients with solid tumors. Relay Therapeutics utilized its Dynamo™ platform to discover RLY-2608, overcoming limitations of traditional orthosteric inhibitors that lack clinically meaningful selectivity between mutant and wild-type PI3Kα.
Trial Collaboration Details
Under the agreement, Pfizer will supply atirmociclib for the study, while Relay Therapeutics will oversee the trial's execution. RLY-2608 is currently being evaluated in a first-in-human trial for patients with advanced solid tumors harboring PIK3CA (PI3Kα) mutations.
