Vanderbilt Clinical Trials

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

Purpose

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.

Condition

Breast Cancer

Eligibility

Eligible Ages: Over 18 Years
Eligible Sex: All
Accepts Healthy 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 Design

Phase: Phase 1/Phase 2
Study Type: Interventional
Allocation: Randomized
Intervention Model: Sequential Assignment
Primary Purpose: Treatment
Masking: None (Open Label)

Arm Groups

Arm	Description	Assigned Intervention
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).	Drug: GDC-4198 GDC-4198 will be administered orally. Other names: RGT-419B RO7840734 Drug: Giredestrant Giredestrant will be administered orally. Other names: GDC-9545 RO7197597
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).	Drug: GDC-4198 GDC-4198 will be administered orally. Other names: RGT-419B RO7840734 Drug: Giredestrant Giredestrant will be administered orally. Other names: GDC-9545 RO7197597
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).	Drug: GDC-4198 GDC-4198 will be administered orally. Other names: RGT-419B RO7840734 Drug: Giredestrant Giredestrant will be administered orally. Other names: GDC-9545 RO7197597
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).	Drug: Giredestrant Giredestrant will be administered orally. Other names: GDC-9545 RO7197597 Drug: Abemaciclib Abemaciclib will be administered orally.

Recruiting Locations

Vanderbilt Breast Center at One Hundred Oaks
Nashville, Tennessee 37204-3609

More Details

Status: Recruiting
Sponsor: Genentech, Inc.

Study Contact

Reference Study ID Number: GO46021 https://forpatients.roche.com/
888-662-6728 (U.S. Only)
global-roche-genentech-trials@gene.com

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.