Relay Therapeutics reports updated interim clinical data for RLY-2608

Relay Therapeutics (RLAY) announced updated interim clinical data for RLY-2608, the first known investigational allosteric, pan-mutant and isoform-selective inhibitor of PI3Kalpha. The updated data show a median progression free survival, or PFS, of 11.4 months in second line, or 2L, patients with PI3Kalpha-mutated, HR+, HER2- locally advanced or metastatic breast cancer who received RLY-2608 600mg twice daily, or BID, + fulvestrant. These data are being presented at the San Antonio Breast Cancer Symposium 2024. RLY-2608 is currently being evaluated in ReDiscover, an ongoing first-in-human study, which was designed to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics and preliminary antitumor activity of RLY-2608 in combination with fulvestrant, and in combination with fulvestrant and ribociclib or atirmociclib, Pfizer’s (PFE) selective CDK4 inhibitor. The RLY-2608 + fulvestrant arm of the study, as of the November 4 interim data cut-off for this arm, had enrolled 118 patients with PI3Kalpha-mutated, HR+, HER2- locally advanced or metastatic breast cancer across all doses in both the dose escalation and dose expansion portions of the study, including 64 patients at the company’s recommended Phase 2 dose (RP2D) of 600mg BID. Among these 64 patients, 31 had a kinase mutation and 33 had a non-kinase mutation. Twelve patients also had a PTEN or AKT co-mutation and were therefore excluded from the efficacy analysis, consistent with the planned pivotal population. Among the 52 RLY-2608 + fulvestrant patients who received the RP2D and did not have a PTEN or AKT co-mutation: The median PFS was 9.2 months for all patients and 11.4 months for 2L patients; Median PFS was 11.4 months for patients with kinase mutations; Clinical benefit rate was 67% across all patients; Among the 31 patients with measurable disease, 12 achieved a partial response; Nearly three quarters of patients experienced tumor reductions; Among the 15 patients with measurable disease who had a kinase mutation, two thirds achieved a PR. RLY-2608 + fulvestrant was generally well tolerated in the 118 patients treated across all doses as of the data cut-off date. Cash balance will be operationalized to preserve ability to complete 2L pivotal study. As of the end of the Q3, cash, cash equivalents and investments were approximately $840M.