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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 | Clinical Trials | Clareo Health

RECRUITINGPHASE1

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

NCT05216432•Relay Therapeutics, Inc.

View on ClinicalTrials.gov

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).

Eligibility

Age

18 - No limit years

Sex

ALL

Healthy Volunteers

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-2608 Single Agent Arm
•\[For Part 1: Escalation\]: Evaluable disease per RECIST v1.1
•\[For Part 2: Expansion\]: Measurable disease per RECIST v1.1
•Disease that is refractory to standard therapy, intolerant to standard therapy, or has declined standard therapy.
•Part 1- histologically or cytologically confirmed diagnosis of unresectable or metastatic solid tumor
•Part 2 - Unresectable or metastatic solid tumor with PIK3CA mutation(s) and one of the following tumor types:
+17 more criteria

Exclusion Criteria

•Prior treatment with:
•1. PI3Kα, AKT, or mTOR inhibitors (all arms except for doublet RLY-2608 + fulvestrant arm, Part 2, Group 2; and triplet combinations, Part 1 dose escalation).
•2. Immune checkpoint inhibitors.
•3. Triplet combinations RLY-2608 + CDK4 or CDK4/6 inhibitor + fulvestrant, Part 2 expansion, Group 2 only:
•i. Prior systemic chemotherapy or antibody drug conjugate for locally advanced or metastatic disease. ii. Prior CDK2, CDK4, or CDK4/6 inhibitor as treatment for locally advanced or metastatic disease.
•iii. Prior treatment with fulvestrant or any selective ER degrader, with the exception of patients who have received fulvestrant or any selective ER degrader as part of neoadjuvant therapy only and with treatment duration ≤6 months.
•Type 1 or Type 2 diabetes requiring antihyperglycemic medication, or fasting plasma glucose ≥140 mg/dL and glycosylated hemoglobin (HbA1c) ≥7.0%.
•History of allergy or hypersensitivity to any components or excipients of PI3K inhibitors. For combination arms only: allergy or hypersensitivity to any components or excipients of fulvestrant, palbociclib, ribociclib, and/or PF-07220060 as appropriate for the combination.
•Past medical history of or ongoing ILD, or pneumonitis requiring intervention. Participants with past history of resolved Grade 1 pneumonitis may be considered, except in triple combination arms.
•The following cardiac criteria:
+3 more criteria

Locations (37)

The University of Arizona Cancer Center

Tucson, Arizona, United States

University of California-San Diego

San Diego, California, United States

HealthONE

Denver, Colorado, United States

Yale University

New Haven, Connecticut, United States

Florida Cancer Specialists

Orlando, Florida, United States

Boca Raton Clinical Research (BRCR) Global

Plantation, Florida, United States

University of Chicago Medical Center

Chicago, Illinois, United States

Community Health Network

Indianapolis, Indiana, United States

Massachusetts General Hospital

Boston, Massachusetts, United States

Dana-Farber Cancer Institute

Boston, Massachusetts, United States

Key Dates

Start Date

December 8, 2021

Primary Completion Date

April 30, 2027

Completion Date

April 30, 2027

Last Updated

September 22, 2025

Enrollment

930

ESTIMATED participants

Conditions

PIK3CA MutationSolid Tumor, AdultHER2-negative Breast CancerBreast CancerMetastatic Breast CancerAdvanced Breast CancerUnresectable Solid Tumor

Interventions

RLY-2608

DRUG

Fulvestrant

DRUG

Palbociclib 125mg

DRUG

Ribociclib 400mg

DRUG

Ribociclib 600mg

DRUG

PF-07220060 100mg

DRUG

PF-07220060 300 mg

DRUG

Contacts

Relay Therapeutics Inc

CONTACT

617-322-0731 ClinicalTrials@relaytx.com

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Data Source & Attribution

This clinical trial information is sourced from ClinicalTrials.gov, a service of the U.S. National Institutes of Health.

ClinicalTrials.gov last update: September 22, 2025Data synced to Clareo: March 29, 2026

Modifications: This data has been reformatted for display purposes. Eligibility criteria have been parsed into inclusion/exclusion sections. Location data has been geocoded to enable distance-based search. For the authoritative and most current information, please visit ClinicalTrials.gov.

Neither the United States Government nor Clareo Health make any warranties regarding the data. Check ClinicalTrials.gov frequently for updates.

View ClinicalTrials.gov Terms and Conditions

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

Inclusion Criteria

Exclusion Criteria

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