A Study Evaluating the Efficacy and Safety of Giredestrant Combined With Palbociclib Compared With Letrozole Combined With Palbociclib in Participants With Estrogen Receptor-Positive, HER2-Negative Locally Advanced or Metastatic Breast Cancer (persevERA Breast Cancer)

• ClinicalTrials.gov Identifier: NCT04546009
• Recruitment Status: Active, not recruiting
• First Posted: September 11, 2020
• Last Update Posted: May 8, 2024
• Sponsor: Hoffmann-La Roche
• Information provided by (Responsible Party): Hoffmann-La Roche

Tracking Information

• First Submitted Date: September 8, 2020
• First Posted Date: September 11, 2020
• Last Update Posted Date: May 8, 2024
• Actual Study Start Date: October 9, 2020
• Estimated Primary Completion Date: March 31, 2025 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: September 8, 2020): Progression-Free Survival (PFS), as Determined by the Investigator According to RECIST v1.1 [ Time Frame: From randomization to the first occurrence of disease progression or death from any cause, whichever occurs first (up to 78 months) ]
• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: April 13, 2023)

• Overall Survival [ Time Frame: From randomization to death from any cause (up to 78 months) ]
• Objective Response Rate, as Determined by the Investigator According to RECIST v1.1 [ Time Frame: From randomization until disease progression or death (up to 78 months) ]
  The objective response rate is defined as the percentage of participants with a complete response or partial response on two consecutive occasions at least (≥)4 weeks apart.
• Duration of Response, as Determined by the Investigator According to RECIST v1.1 [ Time Frame: From first occurrence of documented objective response to disease progression or death from any cause, whichever occurs first (up to 78 months) ]
• Clinical Benefit Rate, as Determined by the Investigator According to RECIST v1.1 [ Time Frame: From randomization until disease progression or death (up to 78 months) ]
  The clinical benefit rate is defined as the percentage of participants with stable disease for ≥24 weeks or a complete response or partial response.
• Time to Confirmed Deterioration in Pain Level, Defined as the Time to First Documented ≥2-Point Increase from Baseline in the 'Worst Pain' Item from the Brief Pain Inventory-Short Form (BPI-SF) Questionnaire [ Time Frame: From Baseline until treatment discontinuation (up to 78 months) ]
• Time to Confirmed Deterioration in Pain Presence and Interference, Defined as the Time to First Documented ≥10-Point Increase from Baseline in the EORTC QLQ-C30 Linearly Transformed Pain Scale Score [ Time Frame: From Baseline until treatment discontinuation (up to 78 months) ]
  EORTC QLQ-C30 = European Organization for Research and Treatment of Cancer Quality-of-Life Questionnaire
• Time to Confirmed Deterioration in Physical Functioning, Defined as the Time to First Documented ≥10-Point Decrease from Baseline in the EORTC QLQ-C30 Linearly Transformed Physical Functioning Scale Score [ Time Frame: From Baseline until treatment discontinuation (up to 78 months) ]
• Time to Confirmed Deterioration in Role Functioning, Defined as the Time to First Documented ≥10-Point Decrease from Baseline in the EORTC QLQ-C30 Linearly Transformed Role Functioning Scale Score [ Time Frame: From Baseline until treatment discontinuation (up to 78 months) ]
• Time to Confirmed Deterioration in Global Health Status and Quality of Life (GHS/QoL), Defined as the Time to First Documented ≥10-Point Decrease from Baseline in the EORTC QLQ-C30 Linearly Transformed GHS/QoL Scale Score [ Time Frame: From Baseline until treatment discontinuation (up to 78 months) ]
• Number of Participants with Adverse Events, Severity Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 (NCI-CTCAE v5.0) [ Time Frame: From treatment initiation until 30 days after the final dose of study treatment (up to 78 months) ]
• Number of Participants with Vital Sign Abnormalities Over the Course of the Study [ Time Frame: Baseline, Days 1 and 15 of Cycles 1 and 2, and Day 1 of each cycle thereafter until treatment discontinuation (1 cycle is 28 days) ]
  Vital signs include respiratory rate, pulse rate, and systolic and diastolic blood pressure while the participant is in a seated position, and temperature.
• Plasma Concentration of Giredestrant at Specified Timepoints [ Time Frame: Days 1 and 15 of Cycle 1; Day 1 of Cycles 2, 4, 8, and 16 (1 cycle is 28 days) ]
• Plasma Concentration of Palbociclib at Specified Timepoints [ Time Frame: Days 1 and 15 of Cycle 1 (1 cycle is 28 days) ]

Original Secondary Outcome Measures (submitted: September 8, 2020)

• Overall Survival [ Time Frame: From randomization to death from any cause (up to 78 months) ]
• Objective Response Rate, as Determined by the Investigator According to RECIST v1.1 [ Time Frame: From randomization until disease progression or death (up to 78 months) ]
  The objective response rate is defined as the percentage of participants with a complete response or partial response on two consecutive occasions at least (≥)4 weeks apart.
• Duration of Response, as Determined by the Investigator According to RECIST v1.1 [ Time Frame: From first occurrence of documented objective response to disease progression or death from any cause, whichever occurs first (up to 78 months) ]
• Clinical Benefit Rate, as Determined by the Investigator According to RECIST v1.1 [ Time Frame: From randomization until disease progression or death (up to 78 months) ]
  The clinical benefit rate is defined as the percentage of participants with stable disease for ≥24 weeks or a complete response or partial response.
• Time to Deterioration in Pain Level, Defined as the Time to First Documented ≥2-Point Increase from Baseline in the 'Worst Pain' Item from the Brief Pain Inventory-Short Form (BPI-SF) Questionnaire [ Time Frame: From Baseline until treatment discontinuation (up to 78 months) ]
• Time to Deterioration in Pain Presence and Interference, Defined as the Time to First Documented ≥10-Point Increase from Baseline in the EORTC QLQ-C30 Linearly Transformed Pain Scale Score [ Time Frame: From Baseline until treatment discontinuation (up to 78 months) ]
  EORTC QLQ-C30 = European Organization for Research and Treatment of Cancer Quality-of-Life Questionnaire
• Time to Deterioration in Physical Functioning, Defined as the Time to First Documented ≥10-Point Decrease from Baseline in the EORTC QLQ-C30 Linearly Transformed Physical Functioning Scale Score [ Time Frame: From Baseline until treatment discontinuation (up to 78 months) ]
• Time to Deterioration in Role Functioning, Defined as the Time to First Documented ≥10-Point Decrease from Baseline in the EORTC QLQ-C30 Linearly Transformed Role Functioning Scale Score [ Time Frame: From Baseline until treatment discontinuation (up to 78 months) ]
• Time to Deterioration in Global Health Status and Quality of Life (GHS/QoL), Defined as the Time to First Documented ≥10-Point Decrease from Baseline in the EORTC QLQ-C30 Linearly Transformed GHS/QoL Scale Score [ Time Frame: From Baseline until treatment discontinuation (up to 78 months) ]
• Number of Participants with Adverse Events, Severity Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 (NCI-CTCAE v5.0) [ Time Frame: From treatment initiation until 30 days after the final dose of study treatment (up to 78 months) ]
• Number of Participants with Vital Sign Abnormalities Over the Course of the Study [ Time Frame: Baseline, Days 1 and 15 of Cycles 1 and 2, and Day 1 of each cycle thereafter until treatment discontinuation (1 cycle is 28 days) ]
  Vital signs include respiratory rate, pulse rate, and systolic and diastolic blood pressure while the participant is in a seated position, and temperature.
• Plasma Concentration of GDC-9545 at Specified Timepoints [ Time Frame: Days 1 and 15 of Cycle 1; Day 1 of Cycles 2, 4, 8, and 16 (1 cycle is 28 days) ]
• Plasma Concentration of Palbociclib at Specified Timepoints [ Time Frame: Days 1 and 15 of Cycle 1 (1 cycle is 28 days) ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Study Evaluating the Efficacy and Safety of Giredestrant Combined With Palbociclib Compared With Letrozole Combined With Palbociclib in Participants With Estrogen Receptor-Positive, HER2-Negative Locally Advanced or Metastatic Breast Cancer (persevERA Breast Cancer)
• Official Title: A Phase III Randomized, Double-Blind, Placebo-Controlled, Multicenter Study Evaluating the Efficacy and Safety of GDC-9545 Combined With Palbociclib Compared With Letrozole Combined With Palbociclib in Patients With Estrogen Receptor-Positive, HER2-Negative Locally Advanced or Metastatic Breast Cancer
• Brief Summary: This Phase III, randomized, double-blind, placebo-controlled, multicenter study will evaluate the efficacy and safety of giredestrant combined with palbociclib compared with letrozole combined with palbociclib in patients with estrogen receptor (ER)-positive, human epidermal growth factor receptor-2 (HER2)-negative locally advanced (recurrent or progressed) or metastatic breast cancer.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Treatment
• Condition: Estrogen Receptor-Positive, HER2-Negative Locally Advanced or Metastatic Breast Cancer

Intervention

• Drug: Giredestrant
  Giredestrant is taken orally once per day on Days 1-28 of each 28-day treatment cycle.
  Other Names:

  • GDC-9545
  • RO7197597
  • RG6171
• Drug: Giredestrant-matched Placebo
  Giredestrant-matched placebo is taken orally once per day on Days 1-28 of each 28-day treatment cycle.
• Drug: Letrozole
  Letrozole 2.5 milligrams (mg) is taken orally once per day on Days 1-28 of each 28-day treatment cycle.
• Drug: Letrozole-matched Placebo
  Letrozole-matched placebo is taken orally once per day on Days 1-28 of each 28-day treatment cycle.
• Drug: Palbociclib
  Palbociclib 125 mg is taken orally once per day on Days 1-21 of each 28-day treatment cycle.
• Drug: LHRH Agonist
  Only premenopausal/perimenopausal and male participants will receive a luteinizing hormone-releasing hormone (LHRH) agonist on Day 1 of each 28-day treatment cycle. The investigator will determine and supply the appropriate LHRH agonist locally approved for use in breast cancer.

Study Arms

• Experimental: Giredestrant + Letrozole-matched Placebo + Palbociclib
  Interventions:

  • Drug: Giredestrant
  • Drug: Letrozole-matched Placebo
  • Drug: Palbociclib
  • Drug: LHRH Agonist
• Active Comparator: Letrozole + Giredestrant-matched Placebo + Palbociclib
  Interventions:

  • Drug: Giredestrant-matched Placebo
  • Drug: Letrozole
  • Drug: Palbociclib
  • Drug: LHRH Agonist

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: April 13, 2023): 992
• Original Estimated Enrollment (submitted: September 8, 2020): 978
• Estimated Study Completion Date: March 18, 2027
• Estimated Primary Completion Date: March 31, 2025 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• For women who are premenopausal or perimenopausal and for men: treatment with approved LHRH agonist therapy for the duration of study treatment
• Locally advanced (recurrent or progressed) or metastatic adenocarcinoma of the breast, not amenable to treatment with curative intent
• Documented ER-positive tumor and HER2-negative tumor, assessed locally
• Patients who have bilateral breast cancers which are both ER-positive and HER2-negative can be included in the study because the metastases are suitably targeted by the study treatments. If patients have bilateral tumors which are of different biomarker status, then proof of the ER and HER2 status of the metastases is required for study entry
• No history of systemic anti-cancer therapy for locally advanced (recurrent or progressed) or metastatic disease
• Disease recurrence from early-stage breast cancer after standard adjuvant endocrine therapy meeting the protocol-defined criteria of having received at least 24 months of treatment without disease progression during treatment and a disease-free interval since the completion of treatment that was greater than 12 months
• Measurable disease as defined per RECIST v.1.1 or bone only disease which must have at least one predominantly lytic bone lesion confirmed by CT or MRI which can be followed
• Eastern Cooperative Oncology Group Performance Status 0-1
• Adequate organ function

Exclusion Criteria:

• Disease recurrence during or within 12 months of completing prior neoadjuvant or adjuvant treatment with any CDK4/6 inhibitor
• Prior treatment with a selective estrogen receptor degrader (SERD)
• Treatment with any investigational therapy within 28 days prior to study treatment
• Treatment with strong CYP3A inhibitors or inducers within 14 days or 5 drug elimination half-lives (whichever is longer) prior to randomization
• Advanced, symptomatic, visceral spread that is at risk of life-threatening complications in the short term
• Known active uncontrolled or symptomatic CNS metastases, carcinomatous meningitis, or leptomeningeal disease
• Active cardiac disease or history of cardiac dysfunction, as defined in the protocol
• Pregnant or breastfeeding

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Argentina, Australia, Austria, Belgium, Brazil, Canada, China, Denmark, France, Germany, Greece, Hong Kong, Hungary, Israel, Italy, Japan, Korea, Republic of, Mexico, New Zealand, Peru, Poland, Portugal, Russian Federation, Spain, Taiwan, Thailand, Turkey, Ukraine, United Kingdom, United States

Administrative Information

• NCT Number: NCT04546009
• Other Study ID Numbers: BO41843; 2020-000119-66 ( EudraCT Number )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Yes

Plan Description

Qualified researchers may request access to individual patient level data through the request platform (www.vivli.org). Further details on Roche's criteria for eligible studies are available here (https://vivli.org/ourmember/roche/).

For further details on Roche's Global Policy on the Sharing of Clinical Information and how to request access to related clinical study documents, see here (https://www.roche.com/innovation/process/clinical-trials/data-sharing/).

• Current Responsible Party: Hoffmann-La Roche
• Original Responsible Party: Same as current
• Current Study Sponsor: Hoffmann-La Roche
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Clinical Trials; Hoffmann-La Roche

• PRS Account: Hoffmann-La Roche
• Verification Date: May 2024