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RecruitingLast updated: 15 May 2026

pionERA: This study is comparing two types of hormone therapy when given in combination with targeted therapy in people with ER+ HER- advanced breast cancerA 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 purpose

Medical clipboardCancer treatment

Tumor type

Breast Cancers Breast

Age

People18+

Trial acronym

pionERA

Clinical summary

Summary

Eligible participants will be randomly assigned to one of two treatment arms. Treatment cycles are 28-days.

In the Experimental Arm, participants will receive Giredestrant hormone therapy + the Investigator's Choice of CDK4/6 inhibitor targeted therapy (either Palbociclib, Ribociclib or Abemaciclib).

Giredestrant (30mg) will be given orally once a day on Days 1-28 of each cycle. If chosen, Abemaciclib (150mg) will be given orally twice daily on Days 1-28, Palbociclib (125mg) will be given orally once daily on Days 1-21, and Ribociclib (600mg) will be given orally once daily on Days 1-21.

In the Active Comparator Arm, participants will receive Fulvestrant hormone therapy + Investigator's Choice of CDK4/6 inhibitor targeted therapy (either Palbociclib, Ribociclib, or Abemaciclib).

Fulvestrant (500mg) will be given intramuscularly on Days 1 and 15 of Cycle 1, and on Day 1 of each subsequent treatment cycle. If chosen, Abemaciclib (150mg) will be given orally twice daily on Days 1-28, Palbociclib (125mg) will be given orally once daily on Days 1-21, and Ribociclib (600mg) will be given orally once daily on Days 1-21.

In both arms, pre/perimenopausal female participants and male participants will receive a luteinizing hormone-releasing hormone (LHRH) agonist locally approved for use in breast cancer on Day 1 of each cycle.

Conditions

This trial is treating people with ER+ HER2- advanced breast cancer who have developed resistance to adjuvant hormone therapy (also called endocrine therapy)

Eligibility

Inclusion

  • 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

  • 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

Inclusion

  • Your cancer has spread to other parts of the body (metastatic) or has grown into nearby parts of the body (locally advanced).
  • Your cancer has not spread to other parts of the body (localised).
  • You have had treatment but your cancer has gotten worse or has not responded to the treatment you have been given.
  • You are able to swallow medication by mouth.
  • You have had a certain type of treatment or surgical procedure.

Exclusion

  • You have certain types of non-cancer medical conditions.
  • You have had certain treatments, surgical procedures or drugs.
Message

Clinical trials have complex eligibility criteria, and other criteria may apply for this trial. Ask your doctor about whether this trial could be right for you.

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More information

Trial Identifiers

Information on this page is partially produced from ClinicalTrials.gov *. View further details about this trial on the registry via the links below:

Trial sponsor

Hoffmann-La Roche

Scientific Title

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

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