A Study to Evaluate Efficacy and Safety of Giredestrant Compared With Fulvestrant (Plus a CDK4/6 Inhibitor), in Participants With ER-Positive, HER2-Negative Advanced Breast Cancer Resistant to Adjuvant Endocrine Therapy (pionERA Breast Cancer)

Roche

Status and phase: Enrolling; Phase 3

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

Treatments: Diagnostic Test: FoundationOne Liquid CDx Assay (F1LCDx); Drug: Giredestrant; Drug: Ribociclib; Drug: Abemaciclib; Drug: Fulvestrant; Drug: LHRH Agonist; Drug: Palbociclib

Study type: Interventional

Funder types: Industry

Identifiers

NCT06065748

CO44657

2022-502980-39-00 (Registry Identifier)

Details and patient eligibility

About

This is a Phase III, randomized, open-label multicenter study that will evaluate the efficacy and safety of giredestrant compared with fulvestrant, both in combination with the investigator's choice of a CDK4/6 inhibitor (palbociclib, ribociclib or abemaciclib), in participants with estrogen receptor-positive (ER+), human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer who have developed resistance to adjuvant endocrine therapy.

Enrollment: 1,050 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Locally advanced or metastatic adenocarcinoma of the breast, not amenable to treatment with curative intent
• Documented estrogen receptor-positive (ER+), HER2-negative (HER2-) tumor assessed locally on the most recent tumor biopsy (or an archived tumor sample if a recent tumor sample is not available for testing)
• Confirmed ESR1 mutation status (ESR1m versus ESR1nmd) in baseline circulating tumor DNA (ctDNA) through central laboratory testing
• Resistance to prior adjuvant endocrine therapy (ET), which is defined as having relapsed with prior standard adjuvant ET, on-treatment after >/=12 months or off-treatment within 12 months of completion. Prior use of neo/adjuvant CDK4/6i is allowed.
• No prior systemic anti-cancer therapy for advanced disease
• Measurable disease as defined per RECIST v.1.1 or non-measurable (including bone-only) disease
• Eastern Cooperative Oncology Group Performance Status (ECOG PS) 0-1
• For pre/perimenopausal women and for men: willing to undergo and maintain treatment with approved LHRH agonist therapy (as per local guidelines) for the duration of study treatment

Exclusion criteria

• Prior systemic therapy (e.g., prior chemotherapy, immunotherapy, or biologic therapy) for locally advanced unresectable or metastatic breast cancer
• Prior treatment with another SERD (e.g., fulvestrant, oral SERDs) or novel ER-targeting agents
• Advanced, symptomatic, visceral spread that is at risk of life-threatening complications in the short term
• Active cardiac disease or history of cardiac dysfunction
• Clinically significant history of liver disease

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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1,050 participants in 2 patient groups

Giredestrant + Investigator's Choice of CDK4/6i

Experimental group

Description:

Participants in the experimental arm will receive giredestrant plus the investigator's choice of CDK4/6 inhibitor (CDK4/6i): palbociclib, ribociclib, or abemaciclib.

Treatment:

Drug: LHRH Agonist

Drug: Palbociclib

Drug: Abemaciclib

Drug: Ribociclib

Drug: Giredestrant

Diagnostic Test: FoundationOne Liquid CDx Assay (F1LCDx)

Fulvestrant + Investigator's Choice of CDK4/6i

Active Comparator group

Description:

Participants in the control arm will receive fulvestrant plus the investigator's choice of CDK4/6 inhibitor (CDK4/6i): palbociclib, ribociclib, or abemaciclib.

Treatment:

Drug: LHRH Agonist

Drug: Palbociclib

Drug: Fulvestrant

Drug: Abemaciclib

Drug: Ribociclib

Diagnostic Test: FoundationOne Liquid CDx Assay (F1LCDx)