Recruiting
Phase 1
Phase 2

GDC-4198, Giredestrant, Abemaciclib

Sponsor:

Genentech, Inc.

Code:

NCT07100106

Conditions

Breast Cancer

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

GDC-4198

Giredestrant

Abemaciclib

Study Details

Brief 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.

Conditions

Breast Cancer

Study ID

NCT07100106

Start date

Oct 7, 2025

Status verified date

Aug, 2026

Completion date

Aug 31, 2028

Anticipated

Primary completion date

Aug 31, 2028

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

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.

Study Design

Enrollment

285 participants

Anticipated

Allocation

Randomized

Intervention Model

Sequential

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Phase Ib: Dose-Finding Stage

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).

experimental: Phase II: Arm A

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).

experimental: Phase II: Arm B

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).

experimental: Phase II: Arm C

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).

Interventions

GDC-4198

GDC-4198 will be administered orally.

Giredestrant

Giredestrant will be administered orally.

Abemaciclib

Abemaciclib will be administered orally.

Primary outcome measure

  • Phase Ib: Incidence and Severity of Adverse Events (AEs) [ Time Frame: Up to 36 months ]
  • Phase Ib: Number of Participants With Dose-Limiting Toxicity (DLTs) [ Time Frame: From Day 1 to Day 28 of Cycle 1 (1 cycle=28 days) ]
  • Phase II: Progression-free Survival (PFS) [ Time Frame: Up to 36 months ]

Central Contacts and Locations

Central contacts

Reference Study ID Number: GO46021 https://forpatients.roche.com/ No attachments to email below.

888-662-6728 (U.S. Only)global-roche-genentech-trials@gene.com

Locations

University of Arizona Cancer Center

Recruiting

Tucson, Arizona, United States, 85724-0001

City of Hope

Recruiting

Duarte, California, United States, 91010

City of Hope - Orange County Lennar Foundation Cancer Center

Recruiting

Irvine, California, United States, 92618

UC San Diego Moores Cancer Center

Recruiting

La Jolla, California, United States, 92093-1503

University of California San Diego Medical Center

Recruiting

San Diego, California, United States, 92103-1911

UCSF Helen Diller Family CCC

Recruiting

San Francisco, California, United States, 94158

Sylvester Comprehensive Cancer Center

Recruiting

Miami, Florida, United States, 33136-1002

Moffitt Cancer Center

Recruiting

Tampa, Florida, United States, 33612

Winship Cancer Institute of Emory University

Recruiting

Atlanta, Georgia, United States, 30322-1013

City of Hope® Cancer Center Chicago

Recruiting

Zion, Illinois, United States, 60099

Barbara Ann Karmanos Cancer Institute

Recruiting

Detroit, Maine, United States, 48201-2013

Maryland Oncology Hematology - Annapolis

Recruiting

Annapolis, Maryland, United States, 21401

Washington University Siteman Cancer Center

Recruiting

St Louis, Missouri, United States, 63110-1010

Rutgers Cancer Institute of New Jersey

Recruiting

New Brunswick, New Jersey, United States, 08901-1914

New York Cancer & Blood Specialists

Recruiting

East Patchogue, New York, United States, 11772

Montefiore Einstein Cancer Center

Recruiting

The Bronx, New York, United States, 10461

Levine Cancer Institute

Recruiting

Charlotte, North Carolina, United States, 28204

Novant Health Cancer Institute

Recruiting

Charlotte, North Carolina, United States, 28204

Oncology Associates of Oregon, P.C

Recruiting

Eugene, Oregon, United States, 97401

Penn State Health Milton S. Hershey Medical Center

Recruiting

Hershey, Pennsylvania, United States, 17033-2360

University of Pennsylvania - Abramson Cancer Center

Recruiting

Philadelphia, Pennsylvania, United States, 19104

UPMC - Hillman Cancer Center

Recruiting

Pittsburgh, Pennsylvania, United States, 15213-3108

Vanderbilt Breast Center at One Hundred Oaks

Recruiting

Nashville, Tennessee, United States, 37204-3609

Texas Oncology (Worth) - USOR

Recruiting

Dallas, Texas, United States, 75246-2003

University of Utah Huntsman Cancer Institute

Recruiting

Salt Lake City, Utah, United States, 84013

Virginia Oncology Associates (Norfolk) - USOR

Recruiting

Norfolk, Virginia, United States, 23502-2800

Princess Margaret Hospital

Recruiting

Toronto, Ontario, Canada, M5G 2M9

More Information

Sponsor

Genentech, Inc.

Last update posted

Aug 10, 2026

Last verified

Aug, 2026

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-04. This information was provided to ClinicalTrials.gov by Genentech, Inc. on 2026-08-10.