A Phase III Randomized, Open-Label Study Evaluating Efficacy and Safety of Giredestrant Compared With Fulvestrant, Both Combined With a CDK4/6 Inhibitor, in Patients With Estrogen Receptor-Positive, HER2-Negative Advanced Breast Cancer With Resistance to Prior Adjuvant Endocrine Therapy

Trial 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.

Receptor status / problem studied:

ER+/HER2 - advanced breast cancer

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

View more trial information

Open for recruitment

Trial Title

pionERA

Diagnosis

Breast cancer

Type of trial

Pharmaceutical

Type of treatement

Medical Oncology

Phase

III

Investigators

Principal Investigator
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