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Purpose

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.

Condition

Eligibility

Eligible Ages
Over 18 Years
Eligible Sex
All
Accepts Healthy Volunteers
No

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

Phase
Phase 1/Phase 2
Study Type
Interventional
Allocation
Randomized
Intervention Model
Sequential Assignment
Primary Purpose
Treatment
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
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).
  • Drug: GDC-4198
    GDC-4198 will be administered orally.
    Other names:
    • RGT-419B
    • RO7840734
  • Drug: Giredestrant
    Giredestrant will be administered orally.
    Other names:
    • GDC-9545
    • RO7197597
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).
  • Drug: GDC-4198
    GDC-4198 will be administered orally.
    Other names:
    • RGT-419B
    • RO7840734
  • Drug: Giredestrant
    Giredestrant will be administered orally.
    Other names:
    • GDC-9545
    • RO7197597
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).
  • Drug: GDC-4198
    GDC-4198 will be administered orally.
    Other names:
    • RGT-419B
    • RO7840734
  • Drug: Giredestrant
    Giredestrant will be administered orally.
    Other names:
    • GDC-9545
    • RO7197597
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).
  • Drug: Giredestrant
    Giredestrant will be administered orally.
    Other names:
    • GDC-9545
    • RO7197597
  • Drug: Abemaciclib
    Abemaciclib will be administered orally.

Recruiting Locations

City of Hope
Duarte, California 91010

City of Hope - Orange County Lennar Foundation Cancer Center
Irvine, California 92618

UC San Diego Moores Cancer Center
La Jolla, California 92093-1503

UCSF Helen Diller Family CCC
San Francisco, California 94158

Sylvester Comprehensive Cancer Center
Miami, Florida 33136-1002

Moffitt Cancer Center
Tampa, Florida 33612

Winship Cancer Institute of Emory University
Atlanta, Georgia 30322-1013

City of Hope® Cancer Center Chicago
Zion, Illinois 60099

Barbara Ann Karmanos Cancer Institute
Detroit, Maine 48201-2013

Washington University Siteman Cancer Center
St Louis, Missouri 63110-1010

Rutgers Cancer Institute of New Jersey
New Brunswick, New Jersey 08901-1914

New York Cancer & Blood Specialists
East Patchogue, New York 11772

Levine Cancer Institute
Charlotte, North Carolina 28204

Novant Health Cancer Institute
Charlotte, North Carolina 28204

University of Pennsylvania - Abramson Cancer Center
Philadelphia, Pennsylvania 19104

UPMC - Hillman Cancer Center
Pittsburgh, Pennsylvania 15213-3108

Vanderbilt Breast Center at One Hundred Oaks
Nashville, Tennessee 37204-3609

Texas Oncology (Worth) - USOR
Dallas, Texas 75246-2003

University of Utah Huntsman Cancer Institute
Salt Lake City, Utah 84013

Virginia Oncology Associates (Norfolk) - USOR
Norfolk, Virginia 23502-2800

More Details

Status
Recruiting
Sponsor
Genentech, Inc.

Study Contact

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

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.