Relay Therapeutics, Inc.
This is an open-label, FIH study designed to evaluate the maximum tolerated dose, recommended Phase 2 dose, safety, tolerability, PK, pharmacodynamics, and preliminary antineoplastic activity of RLY-2608, in advanced solid tumor patients with a Phosphatidylinositol-4,5-bisphosphate-3 kinase, catalytic subunit alpha (PIK3CA) mutation in blood and/or tumor per local assessment. The study will evaluate RLY-2608 as a single agent for patients with unresectable or metastatic solid tumors. It will also evaluate RLY-2608 in combination RLY-2608 + fulvestrant and in triple combination RLY-2608 + fulvestrant + CDK4/6 inhibitor (palbociclib or ribociclib) or CDK4 inhibitor (PF-07220060) for patients with HR+ HER2- locally advanced or metastatic breast cancer. The RLY-2608 single agent arm, RLY-2608 + fulvestrant combination arm, and triple combination arms will have 2 parts: a dose escalation (Part 1) and a dose expansion (Part 2).
Key Inclusion Criteria Patient has ECOG performance status of 0-1 One or more documented primary oncogenic PIK3CA mutation(s) in blood and/or tumor per local assessment Other potentially oncogenic PIK3CA mutations may be considered but must be approved by the Sponsor prior to enrollment. Part 1 \[Escalation\] - Ability to provide archived tumor tissue or be willing to undergo pretreatment tumor biopsy to assess PIK3CA status retrospectively Part 2 \[Expansion\] - Submit tumor tissue prior to study drug initiation for determination of PIK3CA mutation retrospectively. Key Inclusion for RLY-…
RLY-2608 is a mutant-selective, oral PI3Kα inhibitor.
500 mg fulvestrant is administered intramuscularly on Cycle 1 Day 1, Day 15, and Day 1 of each subsequent cycle (where a cycle is 28 days).
125mg palbociclib is taken orally once daily for 28-day cycles that include 21 days of treatment followed by 7 days off treatment.
400mg ribociclib is taken orally once daily for 28-day cycles that include 21 days of treatment followed by 7 days off treatment.
600mg ribociclib is taken orally once daily for 28-day cycles that include 21 days of treatment followed by 7 days off treatment.
PF-07220060 100 mg is taken orally twice daily at the same time with RLY-2608 during each 28-day cycle.
PF-07220060 300 mg is taken orally twice daily at the same time with RLY-2608 during each 28-day cycle.