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RecruitingInterventionalPhase 1/Phase 2

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

NCT ID: NCT07100106Sponsor: Genentech, Inc.Last updated: 2026-06-16

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.

Arms & interventions

  • DrugGDC-4198

    GDC-4198 will be administered orally.

  • DrugGiredestrant

    Giredestrant will be administered orally.

  • DrugAbemaciclib

    Abemaciclib will be administered orally.

Outcome measures

Primary

  • Phase Ib: Incidence and Severity of Adverse Events (AEs)

    Severity of AEs determined according to the CTCAE v5.0 grading scale

    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

Secondary

  • Phase Ib: Objective Response Rate (ORR)

    Time frame: Up to 36 months

  • Phase Ib: Clinical Benefit Rate (CBR)

    Time frame: Up to 36 months

  • Phase II: ORR

    Time frame: Up to 36 months

  • Phase II: Duration of Response (DOR)

    Time frame: Up to 36 months

  • Phase II: CBR

    Time frame: Up to 36 months

  • Phase II: Overall Survival (OS)

    Time frame: Up to 36 months

  • Phase II: OS Rate at 6 Months and 12 Months

    Time frame: Month 6, Month 12

  • Phase II: PFS Rate at 6 Months and 12 Months

    Time frame: Month 6, Month 12

  • Phase II: Incidence and Severity of Adverse Events (AEs)

    Time frame: Up to 36 months

  • Phase II: Plasma Concentration of GDC-4198

    Time frame: Up to 36 months

  • Phase II: Recommended Dose of GDC-4198

    Time frame: Up to 36 months

Eligibility criteria

Sex: AllAge: 18 Years and olderHealthy 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 locations (17)

City of Hope

Duarte, California, 91010

Recruiting

City of Hope - Orange County Lennar Foundation Cancer Center

Irvine, California, 92618

Recruiting

UC San Diego Moores Cancer Center

La Jolla, California, 92093-1503

Recruiting

UCSF Helen Diller Family CCC

San Francisco, California, 94158

Recruiting

Moffitt Cancer Center

Tampa, Florida, 33612

Recruiting

Winship Cancer Institute of Emory University

Atlanta, Georgia, 30322-1013

Recruiting

City of Hope® Cancer Center Chicago

Zion, Illinois, 60099

Recruiting

Barbara Ann Karmanos Cancer Institute

Detroit, Maine, 48201-2013

Recruiting

Washington University Siteman Cancer Center

St Louis, Missouri, 63110-1010

Recruiting

Rutgers Cancer Institute of New Jersey

New Brunswick, New Jersey, 08901-1914

Recruiting

New York Cancer & Blood Specialists

East Patchogue, New York, 11772

Recruiting

Levine Cancer Institute

Charlotte, North Carolina, 28204

Recruiting

University of Pennsylvania - Abramson Cancer Center

Philadelphia, Pennsylvania, 19104

Recruiting

UPMC - Hillman Cancer Center

Pittsburgh, Pennsylvania, 15213-3108

Recruiting

Vanderbilt Breast Center at One Hundred Oaks

Nashville, Tennessee, 37204-3609

Recruiting

Texas Oncology (Worth) - USOR

Dallas, Texas, 75246-2003

Recruiting

Virginia Oncology Associates (Norfolk) - USOR

Norfolk, Virginia, 23502-2800

Recruiting