GIREDESTRANT for Estrogen receptor-positive, HER2-negative advanced breast cancer

Inclusion criteria

• {"criterion_text":"- Confirmed ESR1 mutation status in baseline ctDNA\n- Resistance to prior standard adjuvant ET, defined as relapse on-treatment after ≥ 12 months or off-treatment within 12 months of completion. If adjuvant ET included a CDK4/6i, capecitabine, or S-1 relapse should have occurred ≥ 12 months since completion of CDK4/6i such treatment\n- Measurable disease as defined per RECIST v.1.1 or non-measurable (including bone-only) disease\n- Eastern Cooperative Oncology Group (ECOG) Performance Status 0 - 1\n- Locally advanced or metastatic adenocarcinoma of the breast not amenable to treatment with curative intent, with documented ER+ HER2- status assessed locally based on the most recent tumor biopsy (or archived tumor sample if a recent tumor sample is not available for testing)"}

Exclusion criteria

• {"criterion_text":"- Prior treatment with a SERD (e.g., fulvestrant, investigational)\n- Advanced, symptomatic, visceral spread that is at risk of life-threatening complications\n- Active cardiac disease or history of cardiac dysfunction\n- Clinically significant history of liver disease\n- Prior systemic therapy (e.g., prior chemotherapy, immunotherapy, or biologic therapy) for locally advanced unresectable or metastatic breast cancer. Prior therapy for contralateral, local, and/or regional BC treated with curative surgery is allowed"}

Primary endpoints

• {"endpoint_text":"- 1. Progression-Free Survival (PFS), defined as time from randomization to first occurrence of disease progression (PD), as determined by the investigator according to RECIST v1.1, or death from any cause during the study (whichever occurs first), in the ESR1m subgroup and in the FAS","definition_or_measurement_approach":"Defined as time from randomization to first occurrence of disease progression (PD) per investigator assessment according to RECIST v1.1, or death from any cause during the study (whichever occurs first); assessed in the ESR1m subgroup and in the full analysis set (FAS)."}

Secondary endpoints

• {"endpoint_text":"- 1. PFS in the ESR1nmd subgroup","definition_or_measurement_approach":"Progression-free survival in the ESR1 no mutation detected (ESR1nmd) subgroup"}
• {"endpoint_text":"- 2. OS, defined as the time from randomization to death from any cause","definition_or_measurement_approach":"Overall survival: time from randomization to death from any cause"}
• {"endpoint_text":"- 3. cORR, defined as the proportion of participants with a complete response (CR) or partial response (PR) on two consecutive occasions ≥ 4 weeks apart, as determined by the investigator according to RECIST v1.1","definition_or_measurement_approach":"Confirmed objective response rate (cORR): proportion with CR or PR on two consecutive occasions ≥4 weeks apart per RECIST v1.1 by investigator"}
• {"endpoint_text":"- 4. DOR, 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)","definition_or_measurement_approach":"Duration of response (DOR): time from first documented objective response to PD per RECIST v1.1 by investigator, or death"}
• {"endpoint_text":"- 5. CBR, defined as the proportion of participants with stable disease for ≥ 24 weeks or a CR or PR, as determined by the investigator according to RECIST v1.1","definition_or_measurement_approach":"Clinical benefit rate (CBR): proportion with stable disease ≥24 weeks or CR or PR per RECIST v1.1 by investigator"}
• {"endpoint_text":"- 6. TTCtx, defined as the time from randomization until the start date of chemotherapy or death from any cause (whichever occurs first)","definition_or_measurement_approach":"Time to chemotherapy (TTCtx): time from randomization to start date of chemotherapy or death"}
• {"endpoint_text":"- 7. TTCD in pain severity, defined as the time from randomization to the first documentation of a ≥ 2-point increase from baseline on the “worst pain” item score from the BPI-SF","definition_or_measurement_approach":"Time to confirmed deterioration (TTCD) in pain severity: time from randomization to first documentation of ≥2-point increase from baseline on BPI-SF 'worst pain' item"}
• {"endpoint_text":"- 8. TTCD in pain presence and interference, defined as the time from randomization to the first documentation of a ≥ 10-point increase from baseline in the EORTC QLQ-C30 linearly transformed pain scale score","definition_or_measurement_approach":"TTCD in pain presence/interference: time to first documentation of ≥10-point increase from baseline in EORTC QLQ-C30 pain scale (linearly transformed)"}
• {"endpoint_text":"- 9. TTCD in PF, RF and GHS/QoL, defined as the time from randomization to the first documentation of a ≥ 10-point decrease from baseline in the EORTC QLQ-C30 linearly transformed respective scale scores","definition_or_measurement_approach":"TTCD in physical functioning (PF), role functioning (RF) and global health status/quality of life (GHS/QoL): time to first documentation of ≥10-point decrease from baseline in respective EORTC QLQ-C30 scales"}
• {"endpoint_text":"- 10. Incidence and severity of adverse events, with severity determined according to NCI CTCAE v5.0","definition_or_measurement_approach":"Safety: incidence and severity of AEs graded per NCI CTCAE v5.0"}
• {"endpoint_text":"- 11. Change from baseline in selected vital signs","definition_or_measurement_approach":"Change from baseline in selected vital signs"}
• {"endpoint_text":"- 12. Change from baseline in selected clinical laboratory test results","definition_or_measurement_approach":"Change from baseline in selected clinical laboratory test results"}

Methods

• Physician referral and communication to doctors (materials include physician referral templates and referral letters).
• Digital and social media campaigns (materials labelled 'FB_Instagram_Campaign', 'Social Media Posts').
• Printed recruitment materials: posters, clinical trial leaflets, recruitment brochures (country-specific K1/K2 recruitment documents).
• Patient recruitment vendor support (Swm Partners Limited listed with duty 'Patient Recruitment').
• Site-level outreach (study introduction brochures and visit guides provided to sites).

Austria

Earliest CTIS Part Ii Submission Date

07-12-2023

Latest Decision Or Authorization Date

20-10-2025

Processing Time Days

683

Number Of Sites

5

Number Of Participants

18

Greece

Earliest CTIS Part Ii Submission Date

26-09-2023

Latest Decision Or Authorization Date

20-10-2025

Processing Time Days

755

Number Of Sites

5

Number Of Participants

16

Hungary

Earliest CTIS Part Ii Submission Date

31-10-2023

Latest Decision Or Authorization Date

16-10-2025

Processing Time Days

716

Number Of Sites

4

Number Of Participants

7

Slovenia

Earliest CTIS Part Ii Submission Date

26-09-2023

Latest Decision Or Authorization Date

14-10-2025

Processing Time Days

749

Number Of Sites

1

Number Of Participants

5

Poland

Earliest CTIS Part Ii Submission Date

01-12-2023

Latest Decision Or Authorization Date

17-10-2025

Processing Time Days

686

Number Of Sites

12

Number Of Participants

27

Portugal

Earliest CTIS Part Ii Submission Date

07-12-2023

Latest Decision Or Authorization Date

16-10-2025

Processing Time Days

679

Number Of Sites

5

Number Of Participants

15

Belgium

Earliest CTIS Part Ii Submission Date

01-12-2023

Latest Decision Or Authorization Date

14-10-2025

Processing Time Days

683

Number Of Sites

8

Number Of Participants

17

Finland

Earliest CTIS Part Ii Submission Date

01-12-2023

Latest Decision Or Authorization Date

14-10-2025

Processing Time Days

683

Number Of Sites

2

Number Of Participants

7

Romania

Earliest CTIS Part Ii Submission Date

26-09-2023

Latest Decision Or Authorization Date

20-10-2025

Processing Time Days

755

Number Of Sites

8

Number Of Participants

16

Italy

Earliest CTIS Part Ii Submission Date

26-09-2023

Latest Decision Or Authorization Date

05-12-2025

Processing Time Days

801

Number Of Sites

23

Number Of Participants

65

Germany

Earliest CTIS Part Ii Submission Date

20-12-2023

Latest Decision Or Authorization Date

13-01-2026

Processing Time Days

755

Number Of Sites

10

Number Of Participants

25

France

Earliest CTIS Part Ii Submission Date

01-12-2023

Latest Decision Or Authorization Date

28-01-2026

Processing Time Days

789

Number Of Sites

13

Number Of Participants

38

Spain

Earliest CTIS Part Ii Submission Date

16-11-2023

Latest Decision Or Authorization Date

10-03-2026

Processing Time Days

845

Number Of Sites

15

Number Of Participants

40

Primary sponsor

Full Name

F. Hoffmann-La Roche AG

Organisation Type

Pharmaceutical company

Country Of Registered Address

Switzerland

Contract research organisations

Name

IQVIA RDS Hellas Single Member S.A.

Responsibilities

code:1

Name

IQVIA Limited

Responsibilities

code:1

Name

Almac Clinical Technologies LLC

Responsibilities

code:3

Third parties

• {"country":"Switzerland","full_name":"Labcorp Central Laboratory Services S.a.r.l.","duties_or_roles":"code:4","organisation_type":"Pharmaceutical company"}
• {"country":"Belgium","full_name":"CellCarta","duties_or_roles":"Speciality Laboratory","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"United Kingdom","full_name":"Swm Partners Limited","duties_or_roles":"Patient Recruitment","organisation_type":"Non-Pharmaceutical company"}
• {"country":"Greece","full_name":"IQVIA RDS Hellas Single Member S.A.","duties_or_roles":"code:1","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Foundation Medicine Inc.","duties_or_roles":"code:4","organisation_type":"Pharmaceutical company"}
• {"country":"France","full_name":"Kayentis","duties_or_roles":"Patient Reported Outcome","organisation_type":"Non-Pharmaceutical company"}
• {"country":"United States","full_name":"Almac Clinical Technologies LLC","duties_or_roles":"code:3","organisation_type":"Pharmaceutical company"}
• {"country":"France","full_name":"Median Technologies","duties_or_roles":"Speciality Laboratory","organisation_type":"Pharmaceutical company"}
• {"country":"United Kingdom","full_name":"IQVIA Limited","duties_or_roles":"code:1","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Labcorp Central Laboratory Services LP","duties_or_roles":"code:4","organisation_type":"Pharmaceutical company"}
• {"country":"Germany","full_name":"Foundation Medicine GmbH","duties_or_roles":"Speciality Laboratory","organisation_type":"Pharmaceutical company"}