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)

Phase 3Active Not RecruitingNCT04546009

Hoffmann-La Roche992 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Enrollment

992

Conditions

Estrogen Receptor-Positive, HER2-Negative Locally Advanced or Metastatic Breast Cancer

Interventions

LHRH AgonistDRUG

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.

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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

Locations (255)

Orange Coast Memorial Medical Center

Fountain Valley, California, United States

Long Beach Memorial Medical Center

Long Beach, California, United States

Kaiser Permanente - San Leandro Medical Center

San Leandro, California, United States

Stanford Univ Medical Center

Stanford, California, United States

Kaiser Permanente - Walnut Creek

Walnut Creek, California, United States

Outcomes

Primary Outcomes

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)

Secondary Outcomes

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

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.

Time frame: From randomization until disease progression or death (up to 78 months)

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

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 frame: From randomization until disease progression or death (up to 78 months)

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