RLY-2608 + fulvestrant

RLY-2608 + fulvestrant is a combination therapy being investigated for the treatment of PI3Kα-mutated, hormone receptor-positive (HR+), HER2-negative locally advanced or metastatic breast cancer. RLY-2608 is a first-in-class, mutant-selective PI3Kα inhibitor designed to target a different site than existing PI3Kα inhibitors, potentially reducing toxicity while maintaining efficacy. This combination has demonstrated promising clinical activity with a median progression-free survival (PFS) of 9.2-11.0 months across all patients and 11.4 months in second-line patients. The therapy has shown a high clinical benefit rate of 67% and a confirmed objective response rate of 39% in patients with measurable disease, with particularly impressive efficacy (67% confirmed ORR) in patients with kinase mutations. The combination maintains a favorable safety profile with 92% median dose intensity and mostly low-grade adverse events.