Study of GDC-4198 Alone and With Giredestrant Versus Abemaciclib Plus Giredestrant in Adults With Advanced or Metastatic ER, HER2- Breast Cancer Who Progressed After CDK46 Inhibitor

What this Trial Is About

Researchers are evaluating the safety and effectiveness of GDC-4198 alone and combined with giredestrant compared to abemaciclib combined with giredestrant in participants who have locally advanced or metastatic estrogen receptor-positive ER, HER2-negative breast cancer. This Phase IbII study focuses on participants who have previously experienced progression during or after treatment with a CDK46 inhibitor. The study aims to assess the safety, pharmacokinetics, and activity of these treatments in this population. Participants receive GDC-4198 orally, either alone or in combination with giredestrant at 30 mg daily, following a pre-defined dosing schedule during 28-day cycles until unacceptable side effects, disease progression, or loss of clinical benefit occurs. The study includes a Phase Ib dose-finding stage assessing safety and pharmacokinetics, followed by a Phase II stage that compares the activity and safety of GDC-4198 plus giredestrant against abemaciclib plus giredestrant, which is given orally at 150 mg twice daily with giredestrant 30 mg daily. During the study, participants undergo regular monitoring for adverse events, dose-limiting toxicities, and progression-free survival, with assessments lasting up to 36 months. Researchers measure response rates, clinical benefits, duration of response, overall survival, and plasma concentration of GDC-4198. Safety and activity data are collected throughout treatment cycles, with ongoing evaluations for up to three years to understand the long-term effects and recommended dosing.

A Study to Evaluate the Effect of GDC-4198 Alone and in Combination With Giredestrant Versus Abemaciclib and Giredestrant in Participants With Locally Advanced or Metastatic Estrogen Receptor-Positive (ER+), Human Epidermal Growth Factor Receptor-Negative (HER2-) Breast Cancer