Relay Therapeutics announced interim data from its ReDiscover trial, showcasing the potential of RLY-2608 in treating PI3Kα-mutated, HR+/HER2- metastatic breast cancer. The data, presented on September 9, 2024, highlights a clinically meaningful progression-free survival (PFS) in heavily pre-treated patients.
The ReDiscover trial is a first-in-human study evaluating the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary antitumor activity of RLY-2608. The trial includes RLY-2608 alone, in combination with fulvestrant, and in combination with fulvestrant plus ribociclib or atirmociclib.
Efficacy and Tolerability
As of the August 12, 2024, data cut-off, the RLY-2608 + fulvestrant arm enrolled 118 patients. Among the 64 patients who received the recommended Phase 2 dose (RP2D) of 600mg BID, the median PFS was 9.2 months across all mutations. In patients with kinase mutations, the median PFS was 10.3 months. The clinical benefit rate (CBR) was 57% across all patients.
"These interim data suggest that by selectively targeting mutant PI3Kα, RLY-2608 has the potential to offer a level of benefit to patients that has not previously been possible with existing non-selective medicines, while also having significantly less toxicity," said Don Bergstrom, M.D., Ph.D., President of R&D at Relay Therapeutics.
The combination of RLY-2608 and fulvestrant was generally well-tolerated. The overall tolerability profile consisted of mostly low-grade treatment-related adverse events (TRAEs) that were manageable and reversible. Only two patients discontinued treatment due to TRAEs, and the majority of hyperglycemia was Grade 1, with only one patient experiencing Grade 3 hyperglycemia.
Next Steps for RLY-2608
Relay Therapeutics plans to initiate a pivotal Phase 2 study of RLY-2608 + fulvestrant in 2025, pending regulatory discussions. The company is also progressing two front-line triplet regimens: RLY-2608 + ribociclib + fulvestrant and RLY-2608 + atirmociclib + fulvestrant. Initial safety data for the ribociclib triplet is expected in Q4 2024, with dose expansion cohorts planned for the first half of 2025. The atirmociclib triplet is on track for initiation by the end of 2024.
Lirafugratinib Update
Relay Therapeutics will present updated FGFR2 fusion tumor-agnostic data at the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics in October 2024. The company met with the FDA regarding the regulatory path for lirafugratinib, with the FDA suggesting a new drug application (NDA) in cholangiocarcinoma, followed by a tumor-agnostic supplemental NDA for FGFR2 fusions.
Relay Therapeutics plans to seek a global commercialization partner for lirafugratinib to focus on the remainder of its portfolio.
