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

Cancer Categories

Karmanos Trial ID

NCT ID

Age Group

Scope

Phase

Principal Investigator

Phase Ib Stage

Primary Objective:

Secondary Objectives:

To make a preliminary assessment of the activity of GDC-4198 alone or in combination with giredestrant
To evaluate food-effect on the pharmacokinetics of GDC-4198 and its metabolites

Phase II Stage

Primary Objective:

To compare the efficacy of two dose levels of GDC-4198 in combination with giredestrant to the efficacy of abemaciclib in combination with giredestrant

Secondary Objectives:

To compare the efficacy of two dose levels of GDC-4198 in combination with giredestrant to the efficacy of abemaciclib in combination with giredestrant
To compare the safety of two doses of GDC-4198 in combination with giredestrant to the safety of abemaciclib in combination with giredestrant
To characterize the pharmacokinetics of GDC-4198 and its metabolites in combination with giredestrant
To identify a recommended dose of GDC-4198 for subsequent studies

Eligibility

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 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 anti-cancer therapies, including investigational therapies, within 28 days or 5 drug elimination half -lives, whichever is shorter, prior to initiation of study drug. Treatment with an approved oral endocrine therapy (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.
Poor peripheral venous access
Malabsorption condition or other gastrointestinal (GI) conditions/surgeries that the investigator assesses may significantly interfere with enteral absorption

Locations

4100 John R
Detroit, MI 48201
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Phone: 1-800-527-6266

31995 Northwestern Hwy
Farmington Hills, MI 48334
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Phone: 1-800-527-6266

Applicable Disease Site

Therapies, Drugs, Devices