NCT05216432

First-in-Human Study of Mutant-selective PI3Kα Inhibitor, RLY-2608, as a Single Agent in Patients With Advanced Solid Tumors and in Combination With Endocrine Therapy +/- a CDK4/6 or CDK4 Inhibitor in Patients With Advanced Solid Tumors or Advanced Breast Cancer

• Status: Recruiting
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 930 (estimated)
• Sponsor: Relay Therapeutics, Inc. · Industry
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

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).

Conditions

• PIK3CA Mutation
• Solid Tumor, Adult
• HER2-negative Breast Cancer
• Breast Cancer
• Metastatic Breast Cancer
• Advanced Breast Cancer
• Unresectable Solid Tumor

Interventions

Type	Name	Description
DRUG	RLY-2608	RLY-2608 is a mutant-selective, oral PI3Kα inhibitor.
DRUG	Fulvestrant	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).
DRUG	Palbociclib 125mg	125mg palbociclib is taken orally once daily for 28-day cycles that include 21 days of treatment followed by 7 days off treatment.
DRUG	Ribociclib 400mg	400mg ribociclib is taken orally once daily for 28-day cycles that include 21 days of treatment followed by 7 days off treatment.
DRUG	Ribociclib 600mg	600mg ribociclib is taken orally once daily for 28-day cycles that include 21 days of treatment followed by 7 days off treatment.
DRUG	PF-07220060 100mg	PF-07220060 100 mg is taken orally twice daily at the same time with RLY-2608 during each 28-day cycle.
DRUG	PF-07220060 300 mg	PF-07220060 300 mg is taken orally twice daily at the same time with RLY-2608 during each 28-day cycle.

Timeline

• Start date: 2021-12-08
• Primary completion: 2027-04-30
• Completion: 2027-04-30
• First posted: 2022-01-31
• Last updated: 2025-09-22

Locations

37 sites across 5 countries: United States, Australia, France, Italy, Spain

Regulatory

• FDA-regulated drug study