Relay Therapeutics Posts 44% ORR, Plans Phase 3 Triplet Trial in 2027
Relay Therapeutics reported a 44% objective response rate in heavily pre-treated, CDK4/6-experienced metastatic breast cancer patients receiving zovegalisib, atirmociclib and fulvestrant, with only 3% discontinuation and zero grade 3 hyperglycemia. A randomized Phase 3 frontline trial is slated to begin in early 2027 under a supply agreement with Pfizer.
1. Clinical Efficacy in Heavily Treated Patients
At the April 13 cut-off, 34 evaluable patients with prior CDK4/6 inhibitor exposure in a median third-line setting achieved a 44% objective response rate, consistent across kinase and non-kinase PIK3CA mutations and approaching rates seen with frontline doublets.
2. Safety and Tolerability Profile
In 62 patients at or below the potential Phase 3 dose, only two (3%) discontinued zovegalisib and six (10%) underwent dose reductions for treatment-related adverse events; no grade 3 hyperglycemia occurred, while overall grade 3+ events reached 40%, predominantly neutropenia without any febrile episodes.
3. Phase 3 Frontline Trial Plans
Relay plans a randomized Phase 3 trial in early 2027 for PI3Kα-mutated, HR+/HER2- advanced or metastatic breast cancer, comparing zovegalisib plus atirmociclib and an aromatase inhibitor against a CDK4/6 inhibitor plus AI control, and has secured a supply agreement with Pfizer for study drugs.
4. Pharmacokinetics and Dose Selection
Pharmacokinetic analysis showed atirmociclib increased zovegalisib exposure by approximately 2.5-fold without reciprocal effect, supporting a zovegalisib dose of 150 mg twice daily to maintain concentrations just below IC90 for the Phase 3 trial.