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)

Roche

Status and phase: Active, not recruiting; Phase 3

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

Treatments: Drug: Palbociclib; Drug: Giredestrant; Drug: Letrozole; Drug: Giredestrant-matched Placebo; Drug: Letrozole-matched Placebo; Drug: LHRH Agonist

Study type: Interventional

Funder types: Industry

Identifiers

NCT04546009

2020-000119-66 (EudraCT Number)

BO41843

Details and patient eligibility

About

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.

Enrollment: 992 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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992 participants in 2 patient groups

Giredestrant + Letrozole-matched Placebo + Palbociclib

Experimental group

Treatment:

Drug: LHRH Agonist

Drug: Letrozole-matched Placebo

Drug: Palbociclib

Drug: Giredestrant

Letrozole + Giredestrant-matched Placebo + Palbociclib

Active Comparator group

Treatment:

Drug: LHRH Agonist

Drug: Giredestrant-matched Placebo

Drug: Letrozole

Drug: Palbociclib