Detroit

Researchers are evaluating the safety and effectiveness of GDC-4198 alone and in combination with giredestrant compared to abemaciclib combined with giredestrant in participants with locally advanced or metastatic estrogen receptor-positive (ER+), HER2-negative breast cancer. The study includes two phases: Phase Ib focuses on assessing the safety and how the body processes GDC-4198 alone and with giredestrant, while Phase II compares the activity and safety of the combination of GDC-4198 plus giredestrant against abemaciclib plus giredestrant. Participants must have breast cancer that has progressed during or after treatment with a CDK4/6 inhibitor and approved endocrine therapy. During the study, participants will receive oral doses of GDC-4198, giredestrant, or abemaciclib depending on their assigned group. Phase Ib evaluates GDC-4198 alone and combined with giredestrant, while Phase II randomizes participants to receive either GDC-4198 plus giredestrant or abemaciclib plus giredestrant. Treatment cycles and dosing details are monitored throughout the study to assess safety and drug behavior. Participants will be monitored for adverse events and dose-limiting toxicities during the first 28 days of treatment in Phase Ib, with safety tracked up to 36 months. Phase II will measure progression-free survival over up to 36 months. Assessments include medical evaluations, safety monitoring, and tracking of disease progression. The overall participation time may last up to three years, with regular visits and evaluations to ensure participant safety and collect study data.