About this trial
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.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
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
Disqualifiers
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
Trial design
Sequential
Treatments tested in this trial
GDC-0587
DrugParticipants will receive GDC-0587 orally as per the schedule in the protocol.
Giredestrant
DrugParticipants will receive Giredestrant orally as per the schedule in the protocol.
Omeprazole
DrugParticipants will receive Omeprazole orally as per the schedule in the protocol.
Treatment groups
Trial outcomes
Primary outcomes
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.
Percentage of Participants with Dose-limiting Toxicity (DLTs)
Secondary outcomes
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)
Plasma Concentration of GDC-0587 as a Monotherapy and in Combination With Giredestrant
Plasma Concentration of GDC-0587 with Giredestrant Under Fasted and Fed Conditions
Plasma Concentration of GDC-0587 with Giredestrant Following Multiple-dose Administration, Either Alone or in Combination With Omeprazole
Sponsors and contacts
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