A Study to Evaluate the Efficacy and Safety of Giredestrant Plus Everolimus Compared with the Physician’s Choice of Endocrine Therapy Plus Everolimus in Patients with Estrogen Receptor-Positive, HER2-Negative, Locally Advanced or Metastatic Breast Cancer

Phase 1

• Conditions: Estrogen Receptor (ER)-Positive, HER2-Negative, Locally Advanced or Metastatic Breast Cancer previously treated with a CDK4/6 inhibitor and endocrine therapy; MedDRA version: 23.0Level: PTClassification code: 10083232Term: HER2 negative breast cancer Class: 100000004864; MedDRA version: 23.0Level: LLTClassification code: 10070575Term: Estrogen receptor positive breast cancer Class: 10029104; MedDRA version: 21.1Level: LLTClassification code: 10072740Term: Locally advanced breast cancer Class: 10029104; MedDRA version: 20.0Level: LLTClassification code: 10027475Term: Metastatic breast cancer Class: 10029104; Therapeutic area: Diseases [C] - Neoplasms [C04]

• Registration Number: CTIS2023-506821-12-00
• Lead Sponsor: Genentech Inc.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2024-04-24
• Last Update Posted: 21 August 2024

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 367

Inclusion Criteria

Locally advanced unresectable or metastatic adenocarcinoma of the breast, not amenable to treatment with curative intent, Documented estrogen receptor-positive (ER+) tumor according to American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) or European Society for Medical Oncology (ESMO) guidelines, assessed locally and defined as >= 1% of tumor cells stained positive based on the most recent tumor biopsy (or archived tumor sample), Documented human epidermal growth factor receptor 2 (HER2)-negative tumor assessed locally, Ability to provide a blood sample for circulating-tumor deoxyribonucleic acid (ctDNA) ESR1 mutation status determination by central testing prior to study treatment randomization, Measurable disease as defined per RECIST v.1.1 or evaluable bone metastases which must have at least one predominantly lytic bone lesion confirmed by CT or MRI which can be followed, Resolution of all acute toxic effects of prior anti-cancer therapy or surgical procedures to NCI CTCAE v5.0 Grade = 1

Exclusion Criteria

Prior treatment with another oral selective estrogen receptor degrader (SERD), proteolysis targeting chimera (PROTAC), complete estrogen receptor antagonist (CERAN), novel oral selective estrogen receptor modulator (SERM) or everolimus in any setting. Prior fulvestrant is allowed if treatment was terminated at least 28 days prior to randomization. Prior treatment with tamoxifen is allowed., Progression on more than 2 prior lines of systemic endocrine therapy in the locally advanced unresectable or metastatic breast cancer setting, Treatment with strong Cytochrome P450 3A4 (CYP3A4) inhibitors or inducers within 14 days or 5 drug elimination half-lives prior to randomization, History of any other malignancy other than breast cancer within 5 years prior to screening except for appropriately treated carcinoma in situ of the cervix, nonmelanoma skin carcinoma, papillary thyroid cancer treated with surgery, Stage I endometrial cancer or other non-breast cancers at very low risk of recurrence, Patients known to be positive for human immunodeficiency viruses (HIV) are excluded if they meet any of the following criteria: - CD4+ T-cell count of < 350 cells/µL - Detectable HIV viral load - History of an opportunistic infection within the past 12 months - On stable antiretroviral therapy for < 4 weeks, Active inflammatory bowel disease, chronic diarrhea, short bowel syndrome, or major upper gastrointestinal (GI) surgery including gastric resection, potentially affecting enteral absorption, or a preexisting chronic condition resulting in baseline Grade 2 or higher diarrhea

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified