Relay Therapeutics has announced plans to advance its precision medicine program for breast cancer treatment with the initiation of a pivotal Phase 3 trial for RLY-2608 in combination with fulvestrant, scheduled for mid-2025. The announcement follows successful discussions with the FDA and promising interim clinical data from earlier studies.
Phase 3 Trial Design and Patient Population
The ReDiscover-2 trial will be a randomized, open-label, multicenter study comparing RLY-2608 plus fulvestrant against capivasertib plus fulvestrant in patients with PI3Kα-mutated, HR+/HER2- advanced breast cancer. The study aims to enroll 540 patients who have previously received CDK4/6 inhibitor treatment.
Key eligibility criteria include:
- Prior treatment with frontline endocrine therapy for at least 6 months
- Up to one prior chemotherapy in the metastatic setting
- No prior ADC therapy in the metastatic setting
- HbA1c levels below 7% and fasting plasma glucose under 140 mg/dL
The trial's primary endpoint will assess progression-free survival (PFS) according to RECIST 1.1 criteria, with a hierarchical evaluation in patients with PI3Kα mutations in both kinase domain only and across all mutation types.
Promising Phase 1b Results
Recent interim data from the Phase 1b study of RLY-2608 plus fulvestrant demonstrated encouraging efficacy:
- 11.4-month median PFS in second-line treatment
- 39% confirmed overall response rate in patients with measurable disease
- 67% clinical benefit rate across evaluable patients
- Generally well-tolerated safety profile with predominantly low-grade adverse events
Dosing Optimization
The Phase 3 trial will utilize a 400mg twice-daily dosing regimen of RLY-2608 in the fed state, which has shown equivalent exposure to the 600mg twice-daily fasted dose used in expansion cohorts. This optimization follows the observation of enhanced drug exposure when administered with food.
Expanding Development Program
Beyond the planned Phase 3 trial, Relay Therapeutics is advancing several other development initiatives:
- Investigation of front-line triplet combinations including RLY-2608 with fulvestrant plus either atirmociclib or ribociclib
- Development planning for next-generation endocrine therapy combinations
- Expansion into vascular malformations with a clinical trial planned for Q1 2025
Financial Position
Relay Therapeutics maintains a strong financial foundation with $781.3 million in cash, cash equivalents, and investments as of December 31, 2024. This position is expected to support operations into the second half of 2027, with priority given to funding the ReDiscover-2 Phase 3 trial.
"Our RLY-2608 breast cancer program continued to advance and develop rapidly in 2024," said Sanjiv Patel, M.D., President and CEO of Relay Therapeutics. "With a strong capital position that supports the execution of that pivotal trial, and a team with proven development experience, I am confident in our abilities to meaningfully advance these programs towards patients in oncology and genetic disease areas."
