RecruitingPhase 1NCT05216432

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


Sponsor

Relay Therapeutics, Inc.

Enrollment

930 participants

Start Date

Dec 8, 2021

Study Type

INTERVENTIONAL

Conditions

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

Min Age: 18 Years

Plain Language Summary

Simplified for easier understanding

This study is testing RLY-2608, a new targeted drug that specifically targets a common cancer mutation called PIK3CA, either alone or combined with hormone therapies and CDK inhibitors. It is being tested primarily in people with advanced solid tumors or hormone receptor-positive, HER2-negative breast cancer. **You may be eligible if...** - Your tumor has been tested and found to have a PIK3CA mutation (in blood or tumor tissue) - You are in good physical condition (ECOG score of 0–1) - For breast cancer arms: you have HR+/HER2- advanced or metastatic breast cancer that has been previously treated with endocrine therapy and CDK4/6 inhibitors **You may NOT be eligible if...** - You have diabetes requiring medication, or fasting blood sugar is elevated (glucose of 140 mg/dL or more and HbA1c of 7.0% or more) - You have a history of lung inflammation (ILD or pneumonitis) requiring treatment - You have brain metastases with progressive neurological symptoms - You have had prior treatment with PI3K, AKT, or mTOR inhibitors (with some exceptions) - You have a known allergy to PI3K inhibitors Talk to your doctor to see if this trial is right for you.

This summary was AI-generated to explain the trial in plain language. It is not medical advice. Always discuss eligibility with your doctor before enrolling in a clinical trial.

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Interventions

DRUGRLY-2608

RLY-2608 is a mutant-selective, oral PI3Kα inhibitor.

DRUGFulvestrant

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).

DRUGPalbociclib 125mg

125mg palbociclib is taken orally once daily for 28-day cycles that include 21 days of treatment followed by 7 days off treatment.

DRUGRibociclib 400mg

400mg ribociclib is taken orally once daily for 28-day cycles that include 21 days of treatment followed by 7 days off treatment.

DRUGRibociclib 600mg

600mg ribociclib is taken orally once daily for 28-day cycles that include 21 days of treatment followed by 7 days off treatment.

DRUGPF-07220060 100mg

PF-07220060 100 mg is taken orally twice daily at the same time with RLY-2608 during each 28-day cycle.

DRUGPF-07220060 300 mg

PF-07220060 300 mg is taken orally twice daily at the same time with RLY-2608 during each 28-day cycle.


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

University of Michigan

Ann Arbor, Michigan, United States

Washington University School of Medicine St. Louis

St Louis, Missouri, United States

Renown Regional Medical Center

Reno, Nevada, United States

Rutgers University

New Brunswick, New Jersey, United States

NYU Langone

New York, New York, United States

Columbia University Herbert Irving Comprehensive Cancer Center

New York, New York, United States

Memorial Sloan Kettering

New York, New York, United States

Tennessee Oncology

Nashville, Tennessee, United States

University of Texas Southwestern Medical Center

Dallas, Texas, United States

The University of Texas M.D. Anderson Cancer Center

Houston, Texas, United States

University of Utah- Huntsman Cancer Center

Salt Lake City, Utah, United States

Inova Schar Cancer Center

Fairfax, Virginia, United States

NEXT Virginia

Fairfax, Virginia, United States

UW Carbone Cancer Center

Madison, Wisconsin, United States

St Vincents Hospital

Sydney, New South Wales, Australia

Peter MacCallum Cancer Center

Melbourne, Victoria, Australia

The Alfred Hospital

Melbourne, Victoria, Australia

Centre Léon Bérard

Lyon, Auvergne-Rhône-Alpes, France

Institute Bergonié

Bordeaux, France

Gustave Roussy

Villejuif, France

Istituto Europeo di Oncologia IRCCS

Milan, Italy

Vall d'Hebron Instituto de Oncologia

Barcelona, Barcelona, Spain

START Barcelona

Barcelona, Catalonia, Spain

Instituto Valenciano de Oncologia

Valencia, Valencia, Spain

Institut Catala D'Oncologia - Badalona (ICO Badalona)

Barcelona, Spain

START Madrid - Hospital Fundacion Jimenez Diaz

Madrid, Spain

Hospital Universitario 12 de Octubre

Madrid, Spain

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NCT05216432


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