Trials Today

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