GDC-0587 alone or with giredestrant for advanced ER+/HER2- breast cancer.

A Phase Ia/Ib Dose-Escalation and Expansion Study Evaluating the Safety, Pharmacokinetics, and Activity of GDC-0587 as a Monotherapy and in Combination With Giredestrant in Patients With Locally Advanced Or Metastatic ER-Positive, HER2-Negative Breast Cancer Who Have Previously Progressed During or After CDK4/6 Inhibitor Therapy

This trial tests whether the new CDK4 inhibitor GDC-0587, given alone or with the hormone drug giredestrant, is safe and active in people with advanced ER+/HER2- breast cancer who progressed after CDK4/6 inhibitor treatment.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 136 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Genentech, Inc. (Industry-sponsored)
• Drugs / interventions: chemotherapy
• Locations: 4 sites (Grand Rapids, Michigan and 3 other locations)
• Trial ID: NCT07214662 on ClinicalTrials.gov

What this trial studies

This first-in-human Phase Ia/Ib dose-escalation and expansion trial gives GDC-0587 as monotherapy and in combination with giredestrant to participants with locally advanced or metastatic ER+/HER2- breast cancer who progressed on prior CDK4/6 inhibitors. The study will escalate doses to define safety and pharmacokinetics and then open expansion cohorts to look for anti-tumor activity using RECIST v1.1 criteria. Interventions listed include GDC-0587, the oral selective estrogen receptor degrader giredestrant, and omeprazole (included for concomitant-medication management or interaction assessment). Eligible participants must meet contraception and LHRH agonist requirements and have measurable or evaluable disease.

Who should consider this trial

Good fit: Adults with locally advanced or metastatic ER+/HER2- breast cancer who have progressed during or after CDK4/6 inhibitor therapy, have measurable or evaluable disease, and can meet contraception and LHRH requirements are the intended candidates.

Not a fit: Patients with HER2-positive disease, those who have not received or not progressed on prior CDK4/6 inhibitors, pregnant people, or those with major uncontrolled medical conditions are unlikely to benefit from this experimental regimen.

Why it matters

Potential benefit: If effective, this approach could offer a new treatment option to control tumors in patients whose cancer progressed after prior CDK4/6 inhibitor therapy.

How similar studies have performed: While approved CDK4/6 inhibitors combined with endocrine therapy have proven benefit earlier in ER+ disease, using a novel selective CDK4 inhibitor like GDC-0587, especially after CDK4/6 progression and paired with giredestrant, is largely untested in humans.

Eligibility criteria

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

Where this trial is running

Grand Rapids, Michigan and 3 other locations

• START - Midwest - EDOS — Grand Rapids, Michigan, United States (Recruiting)
• START - San Antonio - EDOS — San Antonio, Texas, United States (Recruiting)
• National Taiwan University Hospital — Taipei, Taipei City, Taiwan (Recruiting)
• National Cheng Kung University Hospital — Tainan, Taiwan (Recruiting)

Study contacts

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

Conditions Breast Cancer