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

Status: Recruiting

Location: See location...

Intervention Type: Drug

Study Type: Interventional

Study Phase: Phase 1/Phase 2

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.

Eligibility

Participation Requirements

Sex: All

Minimum Age: 18

Healthy Volunteers: f

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• 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 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

Locations

United States

New York

New York Cancer & Blood Specialists

RECRUITING

East Patchogue

Contact Information

Primary

Reference Study ID Number: GO46021 https://forpatients.roche.com/

global-roche-genentech-trials@gene.com

888-662-6728 (U.S. Only)

Time Frame

Start Date: 2025-09-30

Estimated Completion Date: 2030-07-31

Participants

Target number of participants: 285

Treatments

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).

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).

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).

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).

Related Therapeutic Areas

Breast Cancer

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