Clinical Trial Results:
An Open-label, Randomized, Non-comparative Phase 2 Study of ARV-471 or Anastrozole in Post-menopausal Women With ER+/HER2- Breast Cancer in the Neoadjuvant Setting
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Summary
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EudraCT number |
2021-005081-17 |
Trial protocol |
DE ES |
Global end of trial date |
25 Jul 2024
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Results information
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Results version number |
v1(current) |
This version publication date |
23 Jul 2025
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First version publication date |
23 Jul 2025
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Other versions |
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Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
ARV-471-BC-201
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT05549505 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
Arvinas Estrogen Receptor, Inc (Arvinas)
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Sponsor organisation address |
5 Science Park 395 Winchester Avenue New Haven, Connecticut, United States, 06511
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Public contact |
Clinical Trials Information Desk, Arvinas Estrogen Receptor, Inc., clinicaltrialinformationdesk@arvinas.com
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Scientific contact |
Clinical Trials Information Desk, Arvinas Estrogen Receptor, Inc., clinicaltrialinformationdesk@arvinas.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
25 Jul 2024
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Is this the analysis of the primary completion data? |
No
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Global end of trial reached? |
Yes
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Global end of trial date |
25 Jul 2024
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
The main goal of this study was to evaluate the biological and clinical activity of vepdegestrant and anastrozole, respectively, in participants with ER+/HER2– breast cancer amenable to definitive surgical resection.
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Protection of trial subjects |
This study was conducted in accordance with the protocol and consensus ethical principles derived from international guidelines including the Declaration of Helsinki, CIOMS International Ethical Guidelines, applicable ICH GCP Guidelines and other applicable laws and regulations.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
15 Feb 2023
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Spain: 100
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Country: Number of subjects enrolled |
Germany: 19
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Country: Number of subjects enrolled |
Georgia: 18
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Country: Number of subjects enrolled |
United States: 15
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Worldwide total number of subjects |
152
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EEA total number of subjects |
119
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
67
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From 65 to 84 years |
83
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85 years and over |
2
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Recruitment
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Recruitment details |
- | ||||||||||||||||||||||||
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Pre-assignment
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Screening details |
A total of 152 participants were enrolled. | ||||||||||||||||||||||||
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Period 1
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Period 1 title |
Overall (overall period)
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Is this the baseline period? |
Yes | ||||||||||||||||||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Not blinded | ||||||||||||||||||||||||
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Arm A: ARV-471 (Experimental) | ||||||||||||||||||||||||
Arm description |
Participants received 200 mg ARV-471 (2*100 mg tablets) once daily for approximately 5.5 months prior to undergoing surgical resection (no later than C6D18 + 14 days). | ||||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||||
Investigational medicinal product name |
ARV-471
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Investigational medicinal product code |
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Other name |
Vepdegestrant, PF-07850327
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
200 mg ARV-471 (2*100 mg tablets) once daily for approximately 5.5 months prior to undergoing surgical resection (no later than C6D18 + 14 days).
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Arm title
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Arm B: Anastrozole | ||||||||||||||||||||||||
Arm description |
Participants received 1 mg Anastrozole tablet orally once daily for approximately 5.5 months prior to undergoing surgical resection (no later than C6D18 + 14 days). | ||||||||||||||||||||||||
Arm type |
Active comparator | ||||||||||||||||||||||||
Investigational medicinal product name |
Anastrozole
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
1 mg Anastrozole tablet once daily for approximately 5.5 months prior to undergoing surgical resection (no later than C6D18 + 14 days).
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Baseline characteristics reporting groups
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Reporting group title |
Arm A: ARV-471 (Experimental)
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Reporting group description |
Participants received 200 mg ARV-471 (2*100 mg tablets) once daily for approximately 5.5 months prior to undergoing surgical resection (no later than C6D18 + 14 days). | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Arm B: Anastrozole
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Reporting group description |
Participants received 1 mg Anastrozole tablet orally once daily for approximately 5.5 months prior to undergoing surgical resection (no later than C6D18 + 14 days). | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Arm A: ARV-471 (Experimental)
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Reporting group description |
Participants received 200 mg ARV-471 (2*100 mg tablets) once daily for approximately 5.5 months prior to undergoing surgical resection (no later than C6D18 + 14 days). | ||
Reporting group title |
Arm B: Anastrozole
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Reporting group description |
Participants received 1 mg Anastrozole tablet orally once daily for approximately 5.5 months prior to undergoing surgical resection (no later than C6D18 + 14 days). | ||
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End point title |
Percent Reduction in Ki-67 Expression From Baseline to Day 15 in Tumor Biopsies [1] | ||||||||||||
End point description |
Tumor biopsy Ki-67 expression (% of tumor cells positive for Ki-67) at baseline and Cycle 1 Day 15 (C1D15) collected. Ki-67 expression assessed by immunohistochemical staining in a central laboratory. Log-transformed Ki-67 after 2 weeks of treatment as percentage of baseline value, ie, ratio between Ki-67 measurements from C1D15 visit and baseline was modelled by a generalized linear model (GLM) with baseline Ki-67 score and tumor size and treatment as co-variates. Treatment effects back transformed into geometric means and Confidence Intervals. Percent change/relative reduction, of Ki-67, 2 weeks post treatment were reported as complement of ratio between Ki-67 measurement from C1D15 and baseline, i.e. 100% × (1-Ki-67 from C1D15/Ki-67 from baseline). Ki-67 Evaluable Set = all enrolled/randomised participants receiving at least one dose of study treatment with evaluable central Ki-67 measurements other than ‘0’ or ‘< 1’ from baseline and evaluable Ki-67 measurements from C1D15 visits.
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End point type |
Primary
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End point timeframe |
Baseline (during screening, prior to Day 1) and Day 15
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| Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Per protocol, no formal comparisons between vepdegestrant and anastrozole or hypotheses testing were planned for this study. |
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs and TEAEs Leading to Study Drug Discontinuation | ||||||||||||||||||
End point description |
An AE is any untoward medical occurrence in a participant, temporally associated with use of study intervention, whether or not considered related to the it. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of study intervention. A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. A TEAE is an AE that emerges or worsens on/after the first dose of ARV-471/Anastrozole to 30 days after the last administration of the study intervention (ie, study drug treatment or surgical resection, whichever occurs last). Safety Analysis Set consisting of all enrolled participants who received at least 1 dose of study intervention.
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End point type |
Secondary
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End point timeframe |
From signing of consent to minimum of 30 days after last administration of study drug (up to approximately 6.5 months)
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| No statistical analyses for this end point | |||||||||||||||||||
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End point title |
Pathologic Stage at the Time of Surgical Resection | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
Local pathological assessment of the tissue from surgical resection (performed after approximately 5.5 months of treatment), at minimum, included pathologic stage (ypT and ypN stage) as described in the Statistical Analysis Plan (SAP). The number of participants with the following disease staging at post-surgery are summarized:
Pathologic Tumor - ypT (ypTx, ypT0, ypTis, ypT1mi, ypT1a, ypT1b, ypT1c, ypT2, ypT3, ypT4a, ypT4b, ypT4c) Pathologocal Lymph Nodes - ypN (ypNX, ypN0, ypN0[i+], ypN0[mol+], ypN1, ypN1mi, ypN1a, ypN1b, ypN1c, ypN2, ypN2a, ypN2b, ypN3, ypN3a, ypN3b, ypN3c).
Full Analysis Set included all the enrolled participants who were randomized.
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End point type |
Secondary
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End point timeframe |
At Cycle 6 Day 18 (approximately 5.5 months), each cycle is 28 days
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| No statistical analyses for this end point | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End point title |
Pathological Complete Response (pCR) Rate at the Time of Surgical Resection | |||||||||
End point description |
pCR is defined as no invasive cancer in the breast and sampled axillary lymph nodes following completion of neoadjuvant systemic therapy (ie, Pathologic Tumor - ypT = ypT0 or ypTis, and Pathologic Lymph Nodes – ypN = ypN0 in the current AJCC staging system). pCR rate is the percentage of participants with pCR. Full Analysis set included all the enrolled participants who were randomized.
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End point type |
Secondary
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End point timeframe |
At Cycle 6 Day 18 (approximately 5.5 months), each cycle is 28 days
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| No statistical analyses for this end point | ||||||||||
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End point title |
Number of Participants With Modified Preoperative Endocrine Prognostic Index (mPEPI) Score of 0 at the Time of Surgical Resection | |||||||||
End point description |
mPEPI score was derived from factors assigned a numerical score following Neoadjuvant endocrine treatment (NET). Total mPEPI score assigned to each patient was the sum of the risk points derived from the pathological (pT) stage, lymph node (pN) stage and Ki67 level. Number of participants with score 0 was reported. Participants with mPEPI score of 0 have pathological stage pT1 or pT2, negative lymph nodes pN0 and proliferation index [Ki-67] of less than or equal to 2.7%. Full Analysis Set included all the enrolled participants who were randomized.
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End point type |
Secondary
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End point timeframe |
At Cycle 6 Day 18 (approximately 5.5 months), each cycle is 28 days
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| No statistical analyses for this end point | ||||||||||
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End point title |
Breast Conserving Surgery (BCS) Rate | ||||||||||||
End point description |
Breast conserving surgery (BCS) Rate is the percentage of participants received breast conserving surgery. Full Analysis Set included all the enrolled participants who were randomized.
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End point type |
Secondary
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End point timeframe |
At Cycle 6 (from Day 141 to Day 168), each cycle is 28 days
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Radiographic Response Per Modified Response Evaluation Criteria in Solid Tumors (mRECIST) in Primary Tumor During Cycle 6 | ||||||||||||||||||||||||
End point description |
The number of participants with Complete Response (CR), Partial Response (PR), Stable Disease (SD), Progressive Disease (PD), Not Evaluable (NE) per mRECIST calculated. CR = disappearance of all target lesions, PR is =>30% decrease in sum of diameters of target lesions, progressive disease (PD) is =>20% increase in sum of diameters of target lesions, stable disease (SD) is <30% decrease or <20% increase in sum of diameters of target lesions. Full Analysis Set included all the enrolled participants who were randomized.
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End point type |
Secondary
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End point timeframe |
At Cycle 6 (from Day 141 to Day 168), each cycle is 28 days
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| No statistical analyses for this end point | |||||||||||||||||||||||||
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End point title |
Percentage Change From Baseline at Cycle 6 Day 1 in Caliper Measurement of the Primary Tumor | ||||||||||||
End point description |
The percentage change from the baseline of the primary breast tumor size in physical exam calculated in caliper measurement. Caliper-based response is the maximum percentage decrease or minimum percentage increase if there is no decrease per participant. Here 'Number of subjects analyzed' signifies those participants who were evaluable for this outcome measure.
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End point type |
Secondary
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End point timeframe |
Baseline (Day 1) and Cycle 6 Day 1 (At Day 141), each cycle is 28 days
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| No statistical analyses for this end point | |||||||||||||
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Adverse events information
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Timeframe for reporting adverse events |
From first study drug administration up to approximately 6.5 months
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Adverse event reporting additional description |
Safety Analysis Set consisting of all enrolled participants who received at least 1 dose of study intervention.
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Assessment type |
Systematic | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
27.1
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Reporting groups
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Reporting group title |
Arm A: ARV-471 (Experimental)
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Reporting group description |
Participants received 200 mg ARV-471 (2*100 mg tablets) once daily for approximately 5.5 months prior to undergoing surgical resection (no later than C6D18 + 14 days). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Arm B: Anastrozole
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Reporting group description |
Participants received 1 mg Anastrozole tablet orally once daily for approximately 5.5 months prior to undergoing surgical resection (no later than C6D18 + 14 days). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 5% | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
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09 Jan 2023 |
- Surgical resection accepted C6D18 ± 14 days instead of C6D18 ± 10 days
- If screening ECG is used for C1D1, it must be done in triplicate and on a vendor machine
- Study drug may be continued beyond C6D18 + 14 days if surgical resection is delayed for non-study related reasons and after discussion with medical monitor.
- Added MRI as preferred imaging modality in Radiographic Imaging Assessment
- Addition of definition of last administration of study intervention as study drug treatment or surgical resection, whichever comes last.
- Clarification that radiographic response will be evaluated per mRECIST.
- Inclusion criteria clarified to participants for whom neoadjuvant endocrine monotherapy is deemed appropriate.
- Exclusion criteria now to exclude patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption. |
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Interruptions (globally) |
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| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| None reported | |||
