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

Official title

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

Overview

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.

Interventions

• Drug GDC-0587
  Participants will receive GDC-0587 orally as per the schedule in the protocol.
• Drug Giredestrant
  Participants will receive Giredestrant orally as per the schedule in the protocol.
• Drug Omeprazole
  Participants will receive Omeprazole orally as per the schedule in the protocol.

Primary outcome measures

• Percentage of Participants with Adverse Events [Time frame: 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) [Time frame: Phase 1a: Days 1-28 of Cycle 1; Phase 1b: Days 1-28 of Cycle 1 (Each cycle is 28 days)]

Secondary outcome measures (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) [Time frame: Up to approximately to 18 months]
• Plasma Concentration of GDC-0587 as a Monotherapy and in Combination With Giredestrant [Time frame: 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 [Time frame: 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 [Time frame: Part 1b: Cycle 1 (Day 11, 12, 20 and 21) (Each cycle is 28 days)]
• Recommended Phase II Dose (RP2D) of GDC-0587 [Time frame: Up to approximately to 18 months]
• Recommended Phase II Dose (RP2D) of GDC-0587 in Combination with Giredestrant [Time frame: Up to approximately to 18 months]

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Non-randomized

Model

Sequential

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 2 centers

• START - Midwest - EDOS — Grand Rapids
• START - San Antonio - EDOS — San Antonio

Taiwan · 2 centers

• National Taiwan University Hospital — Taipei
• National Cheng Kung University Hospital — Tainan

Identifiers

NCT: NCT07214662 · GO46057

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗