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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 | Clinical Trials | Clareo Health

RECRUITINGPHASE1/PHASE2

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

NCT07100106•Genentech, Inc.

View on ClinicalTrials.gov

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

Age

18 - No limit years

Sex

ALL

Healthy Volunteers

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 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 anti-cancer therapies, including investigational therapies, within 28 days or 5 drug elimination half -lives, whichever is shorter, prior to initiation of study drug. Treatment with an approved oral endocrine therapy (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.
•Poor peripheral venous access
•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.

Locations (21)

City of Hope

Duarte, California, United States

City of Hope - Orange County Lennar Foundation Cancer Center

Irvine, 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

UPMC - Hillman Cancer Center

Pittsburgh, Pennsylvania, United States

Key Dates

Start Date

October 7, 2025

Primary Completion Date

August 31, 2028

Completion Date

August 31, 2028

Last Updated

March 12, 2026

Enrollment

285

ESTIMATED participants

Conditions

Breast Cancer

Interventions

GDC-4198

DRUG

Giredestrant

DRUG

Abemaciclib

DRUG

Contacts

Reference Study ID Number: GO46021 https://forpatients.roche.com/

CONTACT

888-662-6728 (U.S. Only)global-roche-genentech-trials@gene.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: March 12, 2026Data 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.

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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

Inclusion Criteria

Exclusion Criteria

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