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
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
Study locations (17)
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
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
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
Virginia Oncology Associates (Norfolk) - USOR
Norfolk, Virginia, 23502-2800