Relay Therapeutics, Inc. (NASDAQ: RLAY) has just announced positive interim data for RLY-2608, the first known investigational allosteric, pan-mutant, and isoform-selective inhibitor of PI3Kα. The data showed that patients with PI3Kα-mutated, HR+, HER2* locally advanced or metastatic breast cancer who received RLY-2608 600mg bid + fulvestrant demonstrated clinically meaningful progression-free survival (PFS).
In the interim data, the 9.2-month median PFS was observed in heavily pre-treated patients with PI3Kα-mutated, HR+/HER2* metastatic breast cancer at the recommended phase 2 dose (RP2D) of RLY-2608. Moreover, a 33% objective response rate (ORR) was recorded across all patients, with 53% ORR in patients with kinase mutations at RP2D.
The study also revealed that patients across all doses had received significant prior therapy in the advanced setting, including at least one prior endocrine therapy and at least one prior CDK4/6 inhibitor. Among the patients who received the RP2D, 45% had received two or more prior lines of therapy, and 52% had received a prior selective estrogen-receptor degrader (SERD), such as fulvestrant or a novel SERD.
The efficacy data in the proposed pivotal population are promising, with a median PFS of 9.2 months across all mutations and 10.3 months among patients with kinase mutations. The clinical benefit rate (CBR) was 57% across all patients, and among the 30 patients with measurable disease, one third achieved a partial response (PR).
The data also showed that RLY-2608 + fulvestrant was generally well tolerated, with mostly low-grade treatment-related adverse events that were manageable and reversible. Only two patients discontinued treatment due to treatment-related adverse events, and only one patient experienced grade 3 hyperglycemia.
In terms of future steps, Relay Therapeutics plans to report initial safety data for RLY-2608 + ribociclib + fulvestrant in the fourth quarter of 2024 and initiate RLY-2608 + ribociclib + fulvestrant triplet dose expansion cohort(s) in the first half of 2025. They also intend to initiate RLY-2608 + atirmociclib (CDK4) + fulvestrant triplet by the end of 2024.
As of the end of the second quarter of 2024, Relay Therapeutics had approximately $688 million in cash, cash equivalents, and investments, which they expect to be sufficient to fund their current operating plan into the second half of 2026, assuming all current programs remain wholly owned and are fully prosecuted. The market has reacted to these announcements by moving the company's shares 52.3% to a price of $9.51. For more information, read the company's full 8-K submission here.
