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)

• Status: Recruiting
• Trial end date: 2028-12-30
• Target enrollment: 0
• Participant gender: All

Summary

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.

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Hoffmann-La Roche
• Treatments: Fulvestrant; Palbociclib

Criteria

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 archived tumor sample)

• Confirmed ESR1 mutation status (ESR1m vs. ESR1nmd) in baseline circulating tumor DNA (ctDNA) through central laboratory testing

• Resistance to prior adjuvant endocrine therapy (ET). 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 bone-only disease

• Eastern Cooperative Oncology Group Performance Status (ECOG PS) 0-1

• For pre/perimenopausal women and for men: treatment with LHRH agonist therapy (as per local guidelines) for the duration of study treatment is required

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