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A Study to Evaluate the Safety, Pharmacokinetics, and Activity of GDC-0587 as a Monotherapy and in Combination With Giredestrant in Participants With Locally Advanced or Metastatic Estrogen Receptor-Positive and Human Epidermal Growth Factor Receptor 2-Negative (ER+/HER2-) Breast Cancer

Purpose

This is a first-in-human, Phase Ia/Ib, dose-escalation and expansion study evaluating the safety, pharmacokinetics, and activity of GDC-0587 (cyclin-dependent kinase-4 [CDK4] inhibitor) as a monotherapy and in combination with giredestrant in participants with locally advanced or metastatic estrogen receptor-positive and human epidermal growth factor receptor 2-negative (ER+/HER2-) breast cancer who have previously progressed during or after CDK 4/6 inhibitor therapy.

Condition

Breast Cancer

Eligibility

Eligible Ages: Over 18 Years
Eligible Sex: All
Accepts Healthy Volunteers: No

Inclusion Criteria

Agreement to adhere to the contraception requirements - For females of childbearing potential ≤60 years of age and males: treatment with luteinizing hormone-releasing hormone (LHRH) agonist therapy beginning at least 2 weeks prior to Cycle 1, Day 1 and agreement to continue LHRH agonist therapy for the duration of the study - Histologically 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 following treatment with an approved CDK 4/6 inhibitor, with or without endocrine therapy, in the locally advanced or metastatic setting - Measurable, or non-measurable but evaluable, disease per RECIST v1.1 - Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1 - Life expectancy ≥6 months - Creatinine clearance ≥60 milliliter per minute (mL/min) (calculated through use of the Cockcroft-Gault formula)

Exclusion Criteria

Pregnant or breastfeeding, or intention of becoming pregnant during the study - 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 - Five or more prior lines of systemic therapy in the locally advanced or metastatic setting - 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 within 7 days prior to initiation of study drug or treatment with fulvestrant or an approved/investigational CDK inhibitor within 21 days prior to initiation of study drug - History of Grade ≥3 adverse event attributed to prior CDK inhibitor therapy that resulted in permanent discontinuation of prior CDK inhibitor therapy - Poor peripheral venous access - Malabsorption condition or other gastrointestinal (GI) conditions/surgeries that the investigator assesses may significantly interfere with enteral absorption - Major surgical procedure within 28 days prior to initiation of study drug - Untreated, active CNS metastases - Infection requiring systemic (i.e., oral, IV, or intramuscular) antibiotics, chronic infection requiring treatment within 1 year prior to screening, or any evidence of current infection - History of malignancy within 3 years prior to screening, except for cancer under investigation in this study - Known history of a clinically significant abnormal ECG

Study Design

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

Arm Groups

Arm	Description	Assigned Intervention
Experimental Phase Ia: GDC-0587 Monotherapy	Participants will receive GDC-0587 orally.	Drug: GDC-0587 Participants will receive GDC-0587 orally as per the schedule in the protocol. Other names: RO7840736 RGT-587
Experimental Phase Ib: GDC-0587 + Giredestrant Cohort	Participants will receive GDC-0587 and Giredestrant orally.	Drug: GDC-0587 Participants will receive GDC-0587 orally as per the schedule in the protocol. Other names: RO7840736 RGT-587 Drug: Giredestrant Participants will receive Giredestrant orally as per the schedule in the protocol. Other names: GDC-9545 RO7197597 RG6171
Experimental Phase Ib: GDC-0587 + Giredestrant Food-Effect and PPI-Effect Cohort	Participants will receive GDC-0587 and Giredestrant orally and also receive omeprazole for evaluating the effects of a proton pump inhibitor (PPI) and food on GDC-0587.	Drug: GDC-0587 Participants will receive GDC-0587 orally as per the schedule in the protocol. Other names: RO7840736 RGT-587 Drug: Giredestrant Participants will receive Giredestrant orally as per the schedule in the protocol. Other names: GDC-9545 RO7197597 RG6171 Drug: Omeprazole Participants will receive Omeprazole orally as per the schedule in the protocol.

Recruiting Locations

START - Midwest - EDOS
Grand Rapids 4994358, Michigan 5001836 49546-7062

START - San Antonio - EDOS
San Antonio 4726206, Texas 4736286 78229-3307

More Details

NCT ID: NCT07214662
Status: Recruiting
Sponsor: Genentech, Inc.

Study Contact

Reference Study ID Number: GO46057 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.