RecruitingPhase 1Phase 2NCT07100106

A Study to Evaluate the Effect of GDC-4198 Alone and in Combination With Giredestrant Versus Abemaciclib and Giredestrant in Participants With Locally Advanced or Metastatic Estrogen Receptor-Positive (ER+), Human Epidermal Growth Factor Receptor-Negative (HER2-) Breast Cancer

A Phase Ib/II Multicenter, Open-Label, Randomized Study Evaluating the Safety, Pharmacokinetics, and Activity of GDC-4198 Alone and in Combination With Giredestrant in Comparison With Abemaciclib and Giredestrant in Participants With Locally Advanced or Metastatic Estrogen Receptor-Positive, HER2-Negative Breast Cancer Who Have Previously Progressed During or After a CDK4/6 Inhibitor

Sponsor

Genentech, Inc.

Enrollment

285 participants

Start Date

Oct 7, 2025

Study Type

INTERVENTIONAL

Conditions

Breast Cancer

Summary

The purpose of this study is to assess the safety of GDC-4198 alone and in combination with giredestrant and also the efficacy of GDC-4198 + giredestrant versus abemaciclib + giredestrant in participants with locally advanced or metastatic ER+, HER2- breast cancer. The study consists of 2 phases: Phase Ib and Phase II. Phase Ib will evaluate the safety and pharmacokinetics (PK) of GDC-4198 alone and in combination with giredestrant. Phase II stage will compare the activity and safety of GDC-4198 and giredestrant with abemaciclib and giredestrant.

Eligibility

Min Age: 18 Years

Plain Language Summary

Simplified for easier understanding

This study is testing two investigational drugs — GDC-4198 (a new targeted therapy) and giredestrant (a next-generation hormone blocker) — alone and in combination with abemaciclib (an existing CDK4/6 inhibitor) for women and men with hormone receptor-positive, HER2-negative advanced breast cancer that has progressed after prior CDK4/6 inhibitor treatment. **You may be eligible if...** - You have locally advanced or metastatic breast cancer that is ER-positive and HER2-negative - Your cancer got worse during or after treatment with a CDK4/6 inhibitor and hormone therapy - You have not received more than one prior line of treatment for advanced disease - You have not had prior chemotherapy for metastatic disease - Your daily functioning is good (ECOG 0–1) - You have a life expectancy of at least 6 months **You may NOT be eligible if...** - Your cancer is spreading rapidly to vital organs and needs immediate chemotherapy - You have had more than one prior treatment line for metastatic disease - You have a history of another cancer in the past 3 years (with some exceptions) - You have significant difficulty absorbing medications by mouth - You have poor venous access 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

DRUGGDC-4198

GDC-4198 will be administered orally.

DRUGGiredestrant

Giredestrant will be administered orally.

DRUGAbemaciclib

Abemaciclib will be administered orally.

Locations(35)

City of Hope

Duarte, California, United States

City of Hope - Orange County Lennar Foundation Cancer Center

Irvine, California, United States

UCSF Helen Diller Family CCC

San Francisco, California, United States

Moffitt Cancer Center

Tampa, Florida, United States

Winship Cancer Institute of Emory University

Atlanta, Georgia, United States

City of Hope® Cancer Center Chicago

Zion, Illinois, United States

Barbara Ann Karmanos Cancer Institute

Detroit, Maine, United States

Washington University Siteman Cancer Center

St Louis, Missouri, United States

Rutgers Cancer Institute of New Jersey

New Brunswick, New Jersey, United States

New York Cancer & Blood Specialists

East Patchogue, New York, United States

University of Pennsylvania - Abramson Cancer Center

Philadelphia, Pennsylvania, United States

UPMC - Hillman Cancer Center

Pittsburgh, Pennsylvania, United States

Vanderbilt Breast Center at One Hundred Oaks

Nashville, Tennessee, United States

Texas Oncology (Worth) - USOR

Dallas, Texas, United States

St Vincent's Hospital Sydney

Darlinghurst, New South Wales, Australia

Cancer Research SA

Adelaide, South Australia, Australia

Hospital do Cancer de Pernambuco - HCP

Recife, Pernambuco, Brazil

Irmandade Da Santa Casa de Misericordia de Porto Alegre

Porto Alegre, Rio Grande do Sul, Brazil

Princess Margaret Hospital

Toronto, Ontario, Canada

Institut Jean Godinot

Reims, Champagne-Ardenne, France

Gustave Roussy

Villejuif, Val-de-Marne, France

Centre Francois Baclesse

Caen, France

Centre Oscar Lambret

Lille, France

Centre Eugene Marquis

Rennes, France

KEM - Evang. Huyssens-Stiftung Essen-Huttrop

Essen, North Rhine-Westphalia, Germany

Gangnam Severance Hospital, Yonsei University Health System

Seoul, Seoul Teugbyeolsi, South Korea

Seoul National University Bundang Hospital

Seongnam-si, South Korea

Asan Medical Center.

Seoul, South Korea

The Catholic University of Korea, Seoul St. Mary's Hospital

Seoul, South Korea

Severance Hospital, Yonsei University Health System

Seoul, South Korea

Instituto de Investigacion Oncologica Vall dHebron (VHIO) - EPON

Barcelona, Spain

Hospital Beata Maria Ana

Madrid, Spain

Hospital General Universitario Gregorio Maranon

Madrid, Spain

Hospital Universitario 12 de Octubre

Madrid, Spain

Hospital Clinico Universitario de Valencia

Valencia, Spain

View Full Details on ClinicalTrials.gov

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NCT07100106

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