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

NCT07214662 | Recruiting Phase 1 FDA Drug

• 1 other identifier: GO46057
• Study Type: interventional
• Target: 136
• Locations: 2 countries
• Sites: 4

Brief Summary

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.

Conditions

Breast Cancer

Outcome Measures

Primary Outcomes (2)

• Percentage of Participants with Adverse Events

  Measured by reporting the incidence and severity using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v5.0 grading scale.

  From Baseline to 30 days after final dose of study treatment (Up to approximately to 18 months)

• Percentage of Participants with Dose-limiting Toxicity (DLTs)

  Phase 1a: Days 1-28 of Cycle 1; Phase 1b: Days 1-28 of Cycle 1 (Each cycle is 28 days)

Secondary Outcomes (6)

• Percentage of Participants With Objective Response Rate (ORR) of Complete Response (CR) or Partial Response (PR) According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1)

  Up to approximately to 18 months

• Plasma Concentration of GDC-0587 as a Monotherapy and in Combination With Giredestrant

  Phase 1a: Cycle 1 (Day 1, 2 15, 16), Cycle 2, 3, 5, 7, 9, 11 (Day 1); Phase 1b: Cycle 1 (Day 1, 2 15, 16), Cycle 2, 3, 5, 7, 9, 11 (Day 1) (Each cycle is 28 days)

• Plasma Concentration of GDC-0587 with Giredestrant Under Fasted and Fed Conditions

  Part 1b: Cycle 1 (Day 1, 2, 4), Cycle 2, 3, 5, 7, 9 and 11 (Day 1) (Each cycle is 28 days)

• Plasma Concentration of GDC-0587 with Giredestrant Following Multiple-dose Administration, Either Alone or in Combination With Omeprazole

  Part 1b: Cycle 1 (Day 11, 12, 20 and 21) (Each cycle is 28 days)

• Recommended Phase II Dose (RP2D) of GDC-0587

  Up to approximately to 18 months

Study Arms (3)

Phase Ia: GDC-0587 Monotherapy

EXPERIMENTAL

Participants will receive GDC-0587 orally.

Drug: GDC-0587

Phase Ib: GDC-0587 + Giredestrant Cohort

EXPERIMENTAL

Participants will receive GDC-0587 and Giredestrant orally.

Drug: GDC-0587; Drug: Giredestrant

Phase Ib: GDC-0587 + Giredestrant Food-Effect and PPI-Effect Cohort

EXPERIMENTAL

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; Drug: Giredestrant; Drug: Omeprazole

Interventions

Giredestrant DRUG

Participants will receive Giredestrant orally as per the schedule in the protocol.

Also known as: GDC-9545, RO7197597, RG6171

Phase Ib: GDC-0587 + Giredestrant Cohort; Phase Ib: GDC-0587 + Giredestrant Food-Effect and PPI-Effect Cohort

GDC-0587 DRUG

Participants will receive GDC-0587 orally as per the schedule in the protocol.

Also known as: RO7840736, RGT-587

Phase Ia: GDC-0587 Monotherapy; Phase Ib: GDC-0587 + Giredestrant Cohort; Phase Ib: GDC-0587 + Giredestrant Food-Effect and PPI-Effect Cohort

Omeprazole DRUG

Participants will receive Omeprazole orally as per the schedule in the protocol.

Phase Ib: GDC-0587 + Giredestrant Food-Effect and PPI-Effect Cohort

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• Genentech, Inc.: lead

Study Sites (4)

START - Midwest - EDOS

Grand Rapids, Michigan, 49546-7062, United States

RECRUITING

START - San Antonio - EDOS

San Antonio, Texas, 78229-3307, United States

RECRUITING

National Taiwan University Hospital

Taipei, Taipei City, 10002, Taiwan

RECRUITING

National Cheng Kung University Hospital

Tainan, 70403, Taiwan

RECRUITING

MeSH Terms

Conditions

Breast Neoplasms

Interventions

giredestrant; Omeprazole

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

2-Pyridinylmethylsulfinylbenzimidazoles; Sulfoxides; Sulfur Compounds; Organic Chemicals; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Benzimidazoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Clinical Trials

  Genentech, Inc.

  STUDY DIRECTOR

Central Study Contacts

Reference Study ID Number: GO46057 https://forpatients.roche.com/

CONTACT

888-662-6728 (U.S. only); global-roche-genentech-trials@gene.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 3, 2025
• First Posted: October 9, 2025
• Study Start: January 13, 2026
• Primary Completion (Estimated): June 1, 2030
• Study Completion (Estimated): June 1, 2030
• Last Updated: May 4, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (2); TW (2)