Recruiting

GDC-4198 and Giredestrant for Advanced ER+, HER2- Breast Cancer

What is being tested

GDC-4198

+ Giredestrant

+ Abemaciclib

Drug

Who is being recruted

Breast Diseases+3

+ Breast Neoplasms

+ Neoplasms

Over 18 Years

+8 Eligibility Criteria

See all eligibility criteria

How is the trial designed

Treatment Study

Phase 1 & 2

Interventional

Study Start: October 2025

See protocol details

Summary

Principal SponsorGenentech, Inc.

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

Last updated: March 13, 2026

Sourced from a government-validated database.Claim as a partner

Study start date: October 7, 2025

Actual date on which the first participant was enrolled.

This clinical trial is focused on testing new treatments for patients with a specific type of breast cancer called estrogen receptor-positive, HER2-negative, which has spread locally or to other parts of the body. The study is important because it aims to find safer and more effective treatment options for those who have already been treated with, but did not respond well to, CDK4/6 inhibitors, a common therapy for this cancer type. The trial will explore the effects of a drug called GDC-4198, both on its own and in combination with another drug called giredestrant, and compare these results with a combination of abemaciclib and giredestrant to determine which is more beneficial for patients. Participants in the study will be divided into two phases. In the first phase (Phase Ib), the safety and how the body processes (pharmacokinetics) GDC-4198, both alone and with giredestrant, will be closely monitored. In the second phase (Phase II), the focus will shift to comparing the effectiveness and safety of the two drug combinations: GDC-4198 with giredestrant, and abemaciclib with giredestrant. Throughout the trial, researchers will carefully assess how patients respond to these treatments and monitor for any side effects, aiming to identify the most effective and safest treatment option.

Official TitleA 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

Principal SponsorGenentech, Inc.

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

Last updated: March 13, 2026

Sourced from a government-validated database.Claim as a partner

Protocol

This section provides details of the study plan, including how the study is designed and what the study is measuring.

Design Details

285 patients to be enrolled

Total number of participants that the clinical trial aims to recruit.

Treatment Study

These studies test new ways to treat a disease, condition, or health issue. The goal is to see if a new drug, therapy, or approach works better or has fewer side effects than existing options.

Eligibility

Researchers look for people who fit a certain description, called eligibility criteria: person's general health condition or prior treatments.

Conditions

Criteria

Any sex

Biological sex of participants that are eligible to enroll.

Over 18 Years

Range of ages for which participants are eligible to join.

Healthy volunteers not allowed

If individuals who are healthy and do not have the condition being studied can participate.

Conditions

Pathology

Breast DiseasesBreast NeoplasmsNeoplasmsNeoplasms by SiteSkin DiseasesSkin and Connective Tissue Diseases

Criteria

4 inclusion criteria required to participate

Life expectancy >= 6 months

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

4 exclusion criteria prevent from participating

Have received more than one-line of therapy for locally advanced or metastatic disease

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

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

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

Study Plan

Find out more about all the medication administered in this study, their detailed description and what they involve.

Treatment Groups

Study Objectives

4 intervention groups are designated in this study

This study does not include a placebo group

Treatment Groups

Group I

Experimental

Participants will receive GDC-4198, higher dose, in combination with giredestrant, 30 mg, orally, daily, as per a pre-defined dosing regimen during each cycle until unacceptable toxicity or disease progression and/or loss of clinical benefit. (1 cycle=28 days).

Group II

Experimental

Participants will receive GDC-4198, lower dose, in combination with giredestrant, 30 mg, orally, daily, as per a pre-defined dosing regimen during each cycle until unacceptable toxicity or disease progression and/or loss of clinical benefit. (1 cycle=28 days).

Group III

Experimental

Participants will receive GDC-4198 as monotherapy and in combination with giredestrant, 30 milligrams (mg), orally, daily, as per a pre-defined dosing regimen during each cycle until unacceptable toxicity or disease progression and/or loss of clinical benefit. (1 cycle=28 days).

Group IV

Experimental

Participants will receive abemaciclib, 150 mg twice daily, in combination with giredestrant, 30 mg, orally, daily, as per a pre-defined dosing regimen during each cycle until unacceptable toxicity or disease progression and/or loss of clinical benefit. (1 cycle=28 days).

Study Objectives

Primary Objectives

Secondary Objectives

Study Centers

These are the hospitals, clinics, or research facilities where the trial is being conducted. You can find the location closest to you and its status.

This study has 21 locations

Recruiting

City of Hope

Duarte, United StatesOpen City of Hope in Google Maps

Recruiting

City of Hope - Orange County Lennar Foundation Cancer Center

Irvine, United States

Recruiting

Moffitt Cancer Center

Tampa, United States

Recruiting

Winship Cancer Institute of Emory University

Atlanta, United States

Recruiting

21 Study Centers