NEW YORK – Relay Therapeutics is ready to advance RLY-2608 into a Phase III trial after the mutant PI3Kα inhibitor plus fulvestrant benefited patients with PI3Kα-altered, hormone receptor-positive, HER2-negative advanced breast cancer in a Phase I trial.
On Monday, Cambridge, Massachusetts-based Relay reported an interim data readout from the ReDiscover clinical study in which it is studying the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary efficacy of RLY-2608 alone, RLY-2608 with fulvestrant, and RLY-2608 with a CDK4/6 inhibitor in patients with locally advanced or metastatic breast cancer. To be eligible for the trial, patients must have declined or be refractory to standard therapy and harbor tumors bearing an oncogenic mutation in PIK3CA, the gene that encodes PI3Kα.
As of Aug. 12, investigators had enrolled 118 patients in the RLY-2608-fulvestrant arm of the trial in both dose-escalation and dose-expansion cohorts, including 64 who are receiving the recommended Phase II dose. Nearly half of the patients had received two or more prior lines of therapy and 52 percent had received a selective estrogen receptor degrader such as fulvestrant.
According to Relay, among 52 patients on the recommended Phase II dose, who also didn't have a PTEN or AKT co-mutation, the median progression-free survival was 9.2 months and the clinical benefit rate was 57 percent. "We will move quickly to share these data with regulators and align on the design of a pivotal study, which we anticipate starting in 2025," Don Bergstrom, president of R&D at Relay, said in a statement.
The RLY-2608-fulvestrant combo was generally well tolerated in the Phase I trial, with only two patients discontinuing treatment due to adverse events. Some patients had hyperglycemia, but the majority of those events were grade 1, with only one patient experiencing grade 3 hyperglycemia and no grade 4 or 5 events.
The risk of hyperglycemia with Novartis' mutant PI3Kα inhibitor Piqray (alpelisib) has hindered its uptake. Relay is hoping to bring to market a competing therapy that by inhibiting only the mutant form of PI3Kα and sparing the wild-type form, carries a lower risk of causing hyperglycemia.