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
Not Applicable
Not yet recruiting
- Conditions
- Breast Cancer
- Interventions
- Registration Number
- NCT07214662
- Lead Sponsor
- Genentech, Inc.
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- NOT_YET_RECRUITING
- Sex
- All
- Target Recruitment
- 136
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
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Phase Ib: GDC-0587 + Giredestrant Food-Effect and PPI-Effect Cohort Giredestrant 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. Phase Ib: GDC-0587 + Giredestrant Food-Effect and PPI-Effect Cohort Omeprazole 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. Phase Ia: GDC-0587 Monotherapy GDC-0587 Participants will receive GDC-0587 orally. Phase Ib: GDC-0587 + Giredestrant Cohort GDC-0587 Participants will receive GDC-0587 and Giredestrant orally. Phase Ib: GDC-0587 + Giredestrant Cohort Giredestrant Participants will receive GDC-0587 and Giredestrant orally. Phase Ib: GDC-0587 + Giredestrant Food-Effect and PPI-Effect Cohort GDC-0587 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.
- Primary Outcome Measures
Name Time Method Percentage of Participants with Adverse Events From Baseline to 30 days after final dose of study treatment (Up to approximately to 18 months) 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) Phase 1a: Days 1-28 of Cycle 1; Phase 1b: Days 1-28 of Cycle 1 (Each cycle is 28 days)
- Secondary Outcome Measures
Name Time Method 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 Recommended Phase II Dose (RP2D) of GDC-0587 in Combination with Giredestrant Up to approximately to 18 months