Jun. 2 at 11:37 AM
$RLAY Relay Therapeutics announces updated data for RLY-2608 with Fulvestrant
Relay Therapeutics announced updated interim clinical data for RLY-2608, the first known investigational allosteric, pan-mutant and isoform-selective inhibitor of PI3Kalpha. The updated data have a median duration of follow-up of 12.5 months and remain consistent with data shared in December 2024. They show a median progression free survival of 11.0 months in second line patients with PI3Kalpha-mutated, HR+, HER2- locally advanced or metastatic breast cancer who received RLY-2608 600mg twice daily + fulvestrant.
These data are being presented today at the American Society of Clinical Oncology 2025 Annual Meeting. 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.
The RLY-2608 + fulvestrant arm of the study, as of the March 26, 2025 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 3 dose of 600mg BID administered in the fasted state. 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. All RLY-2608 + fulvestrant patients across doses had received a significant level of prior therapy in the advanced setting, including at least one prior endocrine therapy and at least one prior CDK4/6 inhibitor. Among the 64 patients who received the RP3D, 44% of patients had received two or more prior lines of therapy.
The RLY-2608 + atirmociclib + fulvestrant arm of the study, initiated in Q4 2024, continues to enroll patients with PI3Kalpha-mutated, HR+, HER2- locally advanced or metastatic breast cancer in dose escalation, as does the RLY-2608 + ribociclib + fulvestrant arm. Among the 52 RLY-2608 + fulvestrant patients who received the RP3D and did not have a PTEN or AKT co-mutation: Median follow-up was 12.5 months. The median PFS was 10.3 months for all patients and 11.0 months for 2L patients. For 2L patients, median PFS was 18.4 months for patients with kinase mutations and 8.5 months for patients with non-kinase mutations.
Clinical benefit rate was 67% across all patients. Among the 31 patients with measurable disease, 12 achieved a partial response. 81% of patients experienced tumor reductions. Among the 15 patients with measurable disease who had a kinase mutation, two thirds achieved a PR. Among the 15 patients who had received prior fulvestrant, 6 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.
The overall tolerability profile consisted of mostly low-grade treatment-related adverse events that were manageable and reversible. Safety outcomes were generally as expected across dose levels based on exposure and consistent with mutant-selective PI3Kalpha inhibition. Among the 64 patients who received the RP3D: The low rate of TRAE-related dose modifications allowed for 92% median dose intensity. Only two patients discontinued treatment due to TRAEs.
The majority of hyperglycemia was Grade 1; only two patients experienced Grade 3 hyperglycemia; no Grade 4-5 hyperglycemia. Only 36% of patients experienced a Grade 3 TRAE; no Grade 4-5 TRAEs. Two front-line triplet regimens are being progressed - one with Pfizer's investigative selective-CDK4 inhibitor atirmociclib and one with the existing CDK4/6 standard-of-care ribociclib. Dose escalation is ongoing for both arms and both are currently at biologically active doses.
