This Phase III, randomized, two-arm, open-label, multicenter study will evaluate the efficacy and safety of giredestrant plus Phesgo compared with Phesgo after induction therapy with Phesgo plus taxane in participants with human epidermal growth factor receptor 2 (HER2)-positive, estrogen receptor (ER)-positive advanced breast cancer (metastatic or locally advanced disease not amenable to curative treatment) who have not previously received a systemic non-hormonal anti-cancer therapy in the advanced setting.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
922
Phesgo will be administered subcutaneously (SC) at a fixed non-weight-based dose. In the induction therapy phase, a loading dose (1200 milligram (mg) pertuzumab, 600 mg trastuzumab, and 30,000 units of recombinant human PH20 hyaluronidase \[rHuPH20\]) will be administered in the first cycle (1 cycle is 21 days). In subsequent cycles, maintenance doses (600 mg pertuzumab, 600 mg trastuzumab, and 20,000 units rHuPH20) will be administered once every 3 weeks (Q3W).
A 30 milligram (mg) capsule of giredestrant will be taken orally once a day on Days 1 to 21 of each 21-day cycle.
During the induction therapy phase, the investigator's choice of taxane-based chemotherapy (i.e., docetaxel or paclitaxel) will be administered after Phesgo. Docetaxel will be administered at 75 milligrams per metre squared of body surface area (mg/m2) intravenously over 60 (±10) minutes on Day 1 of each cycle for 4 to 8 cycles (a cycle is 21 days); this dose may be escalated to 100 mg/m2 if the initial dose was well tolerated.
During the induction therapy phase, the investigator's choice of taxane-based chemotherapy (i.e., docetaxel or paclitaxel) will be administered after Phesgo. Paclitaxel will be administered at 80 milligrams per metre squared of body surface area (mg/m2) intravenously over a minimum of 1 hour on Days 1, 8, and 15 of each cycle for 4 to 8 cycles (a cycle is 21 days); this weekly regimen is considered as one complete cycle whenever 3 weekly doses are given.
A luteinizing hormone-releasing hormone (LHRH) agonist will be administered every 28 days to pre- and peri-menopausal women and all male participants while receiving giredestrant in Arm B. An LHRH agonist may be administered to male participants and pre- and peri-menopausal female participants receiving tamoxifen in Arm A, and should be administered to those receiving an aromatase inhibitor in Arm A. The investigator will determine and supply the appropriate LHRH agonist locally approved for use in breast cancer. The LHRH agonist will be administered according to local prescribing information.
For participants in Arm A, optional endocrine therapy of investigator's choice is allowed based on the standard of care, and it can include an aromatase inhibitor or tamoxifen with or without an LHRH agonist, or gonadal ablation. The decision to include or exclude this option must be made prior to randomization.
Arizona Clinical Research Center, Inc
Tucson, Arizona, United States
Los Angeles Hematology Oncology Medical Group
Los Angeles, California, United States
Cancer Specialists of North Florida
Jacksonville, Florida, United States
Maryland Oncology Hematology - Annapolis
Annapolis, Maryland, United States
St. Joseph Mercy Hospital
Ann Arbor, Michigan, United States
Progression-Free Survival, as Determined by the Investigator According to RECIST v1.1
Time frame: From randomization for maintenance therapy to the first occurrence of disease progression or death from any cause, whichever occurs first (up to 53 months)
Overall Survival
Time frame: From randomization for maintenance therapy to death from any cause (up to 98 months)
Objective Response Rate, as Determined by the Investigator According to RECIST v1.1
The objective response rate is defined as the percentage of participants with a complete response (CR) or partial response (PR) on two consecutive occasions at least 4 weeks apart.
Time frame: From randomization for maintenance therapy to disease progression or death (up to 53 months)
Duration of Response, as Determined by the Investigator According to RECIST v1.1
Time frame: From first occurrence of documented objective response after randomization for maintenance therapy to disease progression or death from any cause, whichever occurs first (up to 53 months)
Clinical Benefit Rate, as Determined by the Investigator According to RECIST v1.1
The clinical benefit rate is defined as the percentage of participants with stable disease for ≥24 weeks or a complete response (CR) or partial response (PR).
Time frame: From randomization for maintenance therapy to disease progression or death (up to 53 months)
Mean Role Functioning Score Over Time, as Assessed Using the European Organisation for Research and Treatment of Cancer Quality of Life-Core 30 (EORTC QLQ-C30) Questionnaire
Time frame: Maintenance Cycles 1 (Baseline), 3, 6, 9, 12, 15, 18, once every 6 cycles from Cycles 24 to 90 (1 cycle is 21 days), treatment discontinuation, every 6 months and every year for Follow-up Years 1-2 and 3-5, respectively (up to 8 years)
Mean Change from Baseline in the Role Functioning Score Over Time, as Assessed Using the European Organisation for Research and Treatment of Cancer Quality of Life-Core 30 (EORTC QLQ-C30) Questionnaire
Time frame: Maintenance Cycles 1 (Baseline), 3, 6, 9, 12, 15, 18, once every 6 cycles from Cycles 24 to 90 (1 cycle is 21 days), treatment discontinuation, every 6 months and every year for Follow-up Years 1-2 and 3-5, respectively (up to 8 years)
Mean Physical Functioning Score Over Time, as Assessed Using the European Organisation for Research and Treatment of Cancer Quality of Life-Core 30 (EORTC QLQ-C30) Questionnaire
Time frame: Maintenance Cycles 1 (Baseline), 3, 6, 9, 12, 15, 18, once every 6 cycles from Cycles 24 to 90 (1 cycle is 21 days), treatment discontinuation, every 6 months and every year for Follow-up Years 1-2 and 3-5, respectively (up to 8 years)
Mean Change from Baseline in the Physical Functioning Score Over Time, as Assessed Using the European Organisation for Research and Treatment of Cancer Quality of Life-Core 30 (EORTC QLQ-C30) Questionnaire
Time frame: Maintenance Cycles 1 (Baseline), 3, 6, 9, 12, 15, 18, once every 6 cycles from Cycles 24 to 90 (1 cycle is 21 days), treatment discontinuation, every 6 months and every year for Follow-up Years 1-2 and 3-5, respectively (up to 8 years)
Mean Global Health Status/Quality of Life Score Over Time, as Assessed Using the European Organisation for Research and Treatment of Cancer Quality of Life-Core 30 (EORTC QLQ-C30) Questionnaire
Time frame: Maintenance Cycles 1 (Baseline), 3, 6, 9, 12, 15, 18, once every 6 cycles from Cycles 24 to 90 (1 cycle is 21 days), treatment discontinuation, every 6 months and every year for Follow-up Years 1-2 and 3-5, respectively (up to 8 years)
Mean Change from Baseline in the Global Health Status/Quality of Life Score Over Time, as Assessed Using the European Organisation for Research and Treatment of Cancer Quality of Life-Core 30 (EORTC QLQ-C30) Questionnaire
Time frame: Maintenance Cycles 1 (Baseline), 3, 6, 9, 12, 15, 18, once every 6 cycles from Cycles 24 to 90 (1 cycle is 21 days), treatment discontinuation, every 6 months and every year for Follow-up Years 1-2 and 3-5, respectively (up to 8 years)
Number of Participants with at Least One Adverse Event, with Severity Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events, version 5 (NCI CTCAE v5.0)
Time frame: From Baseline until 28 days after the final dose of study treatment (up to 8 years, 5 months)
Number of Participants with Abnormalities in Clinical Laboratory Test Results
Time frame: From Baseline until 28 days after the final dose of study treatment (up to 8 years, 5 months)
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