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)

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

Status

Recruiting

Phases

Phase 3

Study type

Interventional

Source

PACTR

Registry ID

PACTR202312893558608

Enrollment

Registered

2023-12-22

Start date

2024-01-15

Completion date

Unknown

Last updated

2026-01-27

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Cancer

Interventions

Giredestrant

Fulvestrant

Eligibility

Sex/Gender

All

Inclusion 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

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

Design outcomes

Primary

Measure	Time frame
Progression-Free Survival (PFS) in the ESR1 mutation (ESR1m) Subgroup [ Time Frame: From randomization to first occurrence of progressive disease (PD) or death (up to 5 years) ] PFS is defined as the time from randomization to the first occurrence of PD, as determined by the investigator according to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1), or death from any cause during the study. PFS in the Full Analysis Set (FAS) Population [ Time Frame: From randomization to first occurrence of PD or death (up to 5 years)	—

Measure

Time frame

Progression-Free Survival (PFS) in the ESR1 mutation (ESR1m) Subgroup [ Time Frame: From randomization to first occurrence of progressive disease (PD) or death (up to 5 years) ] PFS is defined as the time from randomization to the first occurrence of PD, as determined by the investigator according to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1), or death from any cause during the study. PFS in the Full Analysis Set (FAS) Population [ Time Frame: From randomization to first occurrence of PD or death (up to 5 years)

—

Secondary

Measure	Time frame
PFS in the ESR1 no-mutation-detected (ESR1nmd) Subgroup [ Time Frame: From randomization to first occurrence of PD or death (up to 5 years) ] Overall Survival (OS) [ Time Frame: From randomization until death from any cause (up to 5 years) ] OS is defined as the time from randomization to death from any cause. It will be analyzed in the FAS and in the ESR1m and ESR1nmd subgroups. Confirmed Objective Response Rate (cORR) [ Time Frame: From randomization until treatment discontinuation (up to 5 years) ] The cORR is defined as the percentage of participants with a complete response (CR) or partial response (PR) on two consecutive occasions at least 4 weeks apart, as determined by the investigator according to RECIST v1.1. It will be analyzed in the FAS and in the ESR1m and ESR1nmd subgroups. Duration of Response (DOR) [ Time Frame: From the first occurrence of a documented objective response to PD or death (up to 5 years) ] DOR is defined as the time from the first occurrence of a documented objective response to PD, as determined by the investigator according to RECIST v1.1, or death from any cause (whichever occurs first). It will be analyzed in the FAS and in the ESR1m and ESR1nmd subgroups. Clinical Benefit Rate (CBR) [ Time Frame: From randomization until treatment discontinuation (up to 5 years) ] The CBR is defined as the percentage of participants with stable disease for at least (=)24 weeks or a CR or PR, as determined by the investigator according to RECIST v1.1. It will be analyzed in the FAS and in the ESR1m and ESR1nmd subgroups. Time to Chemotherapy [ Time Frame: From randomization until the start of chemotherapy or death (up to 5 years) ] Time to chemotherapy is defined as the time from randomization until the start date of the first chemotherapy or death from any cause (whichever occurs first). It will be analyzed in the FAS and in the ESR1m and ESR1nmd subgroups. ;Time to Confirmed Deterioration (TTCD) in Pain Severity [ Time Frame: Fro	—

Measure

Time frame

PFS in the ESR1 no-mutation-detected (ESR1nmd) Subgroup [ Time Frame: From randomization to first occurrence of PD or death (up to 5 years) ] Overall Survival (OS) [ Time Frame: From randomization until death from any cause (up to 5 years) ] OS is defined as the time from randomization to death from any cause. It will be analyzed in the FAS and in the ESR1m and ESR1nmd subgroups. Confirmed Objective Response Rate (cORR) [ Time Frame: From randomization until treatment discontinuation (up to 5 years) ] The cORR is defined as the percentage of participants with a complete response (CR) or partial response (PR) on two consecutive occasions at least 4 weeks apart, as determined by the investigator according to RECIST v1.1. It will be analyzed in the FAS and in the ESR1m and ESR1nmd subgroups. Duration of Response (DOR) [ Time Frame: From the first occurrence of a documented objective response to PD or death (up to 5 years) ] DOR is defined as the time from the first occurrence of a documented objective response to PD, as determined by the investigator according to RECIST v1.1, or death from any cause (whichever occurs first). It will be analyzed in the FAS and in the ESR1m and ESR1nmd subgroups. Clinical Benefit Rate (CBR) [ Time Frame: From randomization until treatment discontinuation (up to 5 years) ] The CBR is defined as the percentage of participants with stable disease for at least (=)24 weeks or a CR or PR, as determined by the investigator according to RECIST v1.1. It will be analyzed in the FAS and in the ESR1m and ESR1nmd subgroups. Time to Chemotherapy [ Time Frame: From randomization until the start of chemotherapy or death (up to 5 years) ] Time to chemotherapy is defined as the time from randomization until the start date of the first chemotherapy or death from any cause (whichever occurs first). It will be analyzed in the FAS and in the ESR1m and ESR1nmd subgroups. ;Time to Confirmed Deterioration (TTCD) in Pain Severity [ Time Frame: Fro

—

Countries

Kenya

Contacts

Public ContactKatrina Budesha

Clinical Operations Lead

katrina.budesha@roche.com+447721051097

Outcome results

None listed

Source: PACTR (via WHO ICTRP) · Data processed: Feb 4, 2026