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NCT07100106PHASE1, PHASE2Recruiting

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

Genentech, Inc.

Start Date

10/7/2025

Completion Date

8/31/2028

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 Criteria

Age Range: 18 years to No maximum

Inclusion Criteria: * Histologically and/or cytologically confirmed adenocarcinoma of the breast that is locally advanced or metastatic. * Previously documented ER+ and HER2- tumor according to American Society of Clinical Oncology (ASCO)/ College of American Pathologists (CAP) or European Society of Medical Oncology (ESMO) guidelines or any national guidelines with criteria conforming to ASCO/CAP or ESMO guidelines. * Disease progression during or after treatment with an approved cyclin-dependent kinase 4/6 (CDK4/6) inhibitor and approved endocrine therapy (ET) in the locally advanced or metastatic setting. * Measurable or non-measurable evaluable, disease per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1). * Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1. * Life expectancy \>= 6 months. Exclusion Criteria: * Advanced, symptomatic, visceral spread that is at risk of life-threatening complications in the short term appropriate for treatment with cytotoxic chemotherapy at time of entry into the study, as per national or local treatment guidelines. * Have received more than one-line of therapy for locally advanced or metastatic disease. * Have received prior chemotherapy for metastatic breast cancer. * Treatment with an approved oral ET within 7 days prior to initiation of study drug; treatment with fulvestrant or an approved CDK4/6 inhibitor within 21 days prior to initiation of study drug. * Malabsorption condition or other gastrointestinal (GI) conditions/surgeries that the investigator assesses may significantly interfere with enteral absorption * History of malignancy within 3 years prior to screening, except for cancer under investigation in this study and malignancies with a negligible risk of metastasis or death. * Known allergy or hypersensitivity to any component of the study treatments.

Interventions

DRUG

GDC-4198

DRUG

Giredestrant

DRUG

Abemaciclib

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Conditions

Breast Cancer

Locations

City of Hope

Duarte, California 91010

United States

City of Hope - Orange County Lennar Foundation Cancer Center

Irvine, California 92618

United States

UC San Diego Moores Cancer Center

La Jolla, California 92093-1503

United States

UCSF Helen Diller Family CCC

San Francisco, California 94158

United States

Sylvester Comprehensive Cancer Center

Miami, Florida 33136-1002

United States

Moffitt Cancer Center

Tampa, Florida 33612

United States

Winship Cancer Institute of Emory University

Atlanta, Georgia 30322-1013

United States

City of Hope® Cancer Center Chicago

Zion, Illinois 60099

United States

Barbara Ann Karmanos Cancer Institute

Detroit, Maine 48201-2013

United States

Washington University Siteman Cancer Center

St Louis, Missouri 63110-1010

United States

Rutgers Cancer Institute of New Jersey

New Brunswick, New Jersey 08901-1914

United States

New York Cancer & Blood Specialists

East Patchogue, New York 11772

United States

Levine Cancer Institute

Charlotte, North Carolina 28204

United States

Novant Health Cancer Institute

Charlotte, North Carolina 28204

United States

University of Pennsylvania - Abramson Cancer Center

Philadelphia, Pennsylvania 19104

United States

UPMC - Hillman Cancer Center

Pittsburgh, Pennsylvania 15213-3108

United States

Vanderbilt Breast Center at One Hundred Oaks

Nashville, Tennessee 37204-3609

United States

Texas Oncology (Worth) - USOR

Dallas, Texas 75246-2003

United States

University of Utah Huntsman Cancer Institute

Salt Lake City, Utah 84013

United States

Virginia Oncology Associates (Norfolk) - USOR

Norfolk, Virginia 23502-2800

United States

St Vincent's Hospital Sydney

Darlinghurst, New South Wales 2010

Australia

Cancer Research SA

Adelaide, South Australia 5000

Australia

Hospital do Cancer de Pernambuco - HCP

Recife, Pernambuco 50040-000

Brazil

ONCOSITE Centro de Pesquisa Clínica Em Oncologia

Ijuí, Rio Grande do Sul 98700-000

Brazil

Irmandade Da Santa Casa de Misericordia de Porto Alegre

Porto Alegre, Rio Grande do Sul 90035-074

Brazil

Hospital de Clinicas de Porto Alegre (HCPA) - PPDS

Porto Alegre, Rio Grande do Sul 90560-030

Brazil

Instituto Do Câncer Do Estado de São Paulo Octávio Frias de Oliveira - ICESP

São Paulo, 01246-000

Brazil

Princess Margaret Hospital

Toronto, Ontario M5G 2M9

Canada

Shandong Cancer Hospital

Jinan, SD 250117

China

Fudan University Shanghai Cancer Center - Pudong Campus

Shanghai, Shanghai Municipality 201321

China

Institut Jean Godinot

Reims, Champagne-Ardenne 51100

France

Gustave Roussy

Villejuif, Val-de-Marne 94805

France

Centre Francois Baclesse

Caen, 14076

France

Centre Oscar Lambret

Lille, 59020

France

Centre Eugene Marquis

Rennes, 35042

France

KEM - Evang. Huyssens-Stiftung Essen-Huttrop

Essen, North Rhine-Westphalia 45136

Germany

Universitatsklinikum Hamburg-Eppendorf

Hamburg, 20251

Germany

IRCCS Azienda Ospedaliero Universitaria di Bologna

Bologna, Emilia-Romagna 40138

Italy

Istituto Romagnolo per lo Studio dei Tumori Dino Amadori - IRST S.r.l - PPDS

Meldola, Emilia-Romagna 47014

Italy

ASST degli Spedali Civili di Brescia - Spedali Civili di Brescia

Brescia, Lombardy 25123

Italy

Ospedale San Raffaele S.r.l. - PPDS

Milan, Lombardy 20132

Italy

Gangnam Severance Hospital, Yonsei University Health System

Seoul, Seoul Teugbyeolsi 6273

South Korea

Seoul National University Bundang Hospital

Seongnam-si, 13620

South Korea

Seoul National University Hospital

Seoul, 03080

South Korea

Asan Medical Center.

Seoul, 05505

South Korea

Severance Hospital, Yonsei University Health System

Seoul, 3722

South Korea

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

Seoul, 6591

South Korea

Instituto de Investigacion Oncologica Vall dHebron (VHIO) - EPON

Barcelona, 08035

Spain

Hospital Beata Maria Ana

Madrid, 28007

Spain

Hospital General Universitario Gregorio Maranon

Madrid, 28007

Spain

Hospital Universitario 12 de Octubre

Madrid, 28041

Spain

Hospital Clinico Universitario de Valencia

Valencia, 46010

Spain