Clinical trial NCT05549505
Conditions: Breast Cancer
Keywords: Early breast cancer Localized breast cancer Untreated breast cancer Pre-operative breast cancer Treatment-naïve breast cancer Neoadjuvant Estrogen receptor Estrogen receptor positive ER+ Hormone positive Hormone receptor positive HR+ human epidermal growth factor receptor 2 negative HER2- ARV-471 Anastrozole Arimidex Aromatase inhibitor Vepdegestrant PF-07850327
Sponsor: Arvinas Inc.
Start date: 2023-02-15; Completion date: 2024-07-25
Enrollment: 152 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
This trial is a Phase 2 neoadjuvant study evaluating ARV-471 or anastrozole in post-menopausal women with estrogen receptor positive/ human epidermal growth factor receptor 2 (ER+/HER2)- localized breast cancer.

Detailed description:
This is a Phase 2, open-label, randomized, non-comparative proof of concept study of ARV-471 or anastrozole in participants with ER+/HER2- breast cancer amenable to definitive surgical resection. The main goal of this study is to evaluate the biological activity of ARV-471 and anastrozole, respectively.

Arms: arm 1: 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 Cycle 6 Day 18 \[C6D18\] + 14 days). arm 2: 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).
Interventions: intervention 1: ARV-471 intervention 2: Anastrozole intervention 3: Surgical resection of breast tumor
Intervention descriptions: intervention 1: 100 mg tablet intervention 2: 1 mg tablet intervention 3: Surgical resection approximately 5.5 months after starting treatment (C6D18 ± 14 days)

Protocol documents:
Prot_000.pdf: 
ARV-471 (PF-07850327) 
 
Study ARV-471-BC-201 
Global Amendment #1 
 
CONFIDENTIAL 
 
 
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 
Protocol Number: 
ARV-471-BC-201 
Study Intervention Number: 
ARV-471 (PF-07850327) 
Study Intervention Name: 
NA 
Phase: 
2 
US IND Number: 
140264 
EudraCT Number: 
2021-005081-17  
Brief Title: A Phase 2 neoadjuvant study of ARV-471 and anastrozole 
Sponsor Name:  
Arvinas Estrogen Receptor, Inc 
(Arvinas) 
Legal Registered Address:  
5 Science Park, 395 Winchester Ave, 
New Haven, CT 06510 
Date of Original Protocol:  
27 May 2022 
Date of Global Amendment #1: 
09 Jan 2023 
 
This document is the confidential and proprietary information of Arvinas Estrogen Receptor, Inc. (Arvinas). 
By reviewing this document, you agree to keep it confidential and to use and disclose it solely for the 
purpose of assessing whether your organization will participate in and/or the performance of the proposed 
sponsored study. Any permitted disclosures will be made only on a confidential “need to know” basis within 
your organization or to your independent ethics committee(s). Any other use, copying, disclosure or 
dissemination of this information is strictly prohibited unless expressly authorized in writing by Arvinas. 
Any supplemental information (eg, amendments) that may be added to this document is also confidential and 
proprietary to Arvinas and must be kept in confidence in the same manner as the contents of this document. 
Any person who receives this document without due authorization from Arvinas is requested to return it to 
Arvinas or promptly destroy it. All other rights reserved. References to Arvinas in this protocol may apply to 
partners to which Arvinas has transferred obligations, eg, a contract research organization. 
 


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TABLE OF CONTENTS 
LIST OF TABLES .............................................................................................................. 10 
LIST OF FIGURES ............................................................................................................. 10 
DOCUMENT HISTORY .................................................................................................... 11 
1. PROTOCOL SUMMARY ............................................................................................... 14 
1.1. Synopsis .................................................................................................................... 14 
1.2. Schema ..................................................................................................................... 21 
1.3. Schedule of Activities ............................................................................................... 22 
2. INTRODUCTION ........................................................................................................... 27 
2.1. Study Rationale ......................................................................................................... 27 
2.2. Background ............................................................................................................... 28 
2.2.1. Clinical Overview ......................................................................................... 29 
2.2.1.1. ARV-471 ..................................................................................... 29 
2.2.1.2. Anastrozole .................................................................................. 34 
2.3. Benefit/Risk Assessment ........................................................................................... 35 
2.3.1. Risk Assessment ........................................................................................... 35 
3. OBJECTIVES, ENDPOINTS, AND ESTIMANDS ......................................................... 36 
4. STUDY DESIGN ............................................................................................................ 37 
4.1. Overall Design .......................................................................................................... 37 
4.2. Scientific Rationale for Study Design ........................................................................ 37 
4.2.1. Rationale for Selection of Patient Population................................................. 37 
4.2.2. Rationale for Selection of Control Arm ......................................................... 37 
4.2.3. Rationale for Duration of Treatment .............................................................. 38 


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4.2.4. Collection of Retained Research Samples...................................................... 38 
4.3. Justification for Dose ................................................................................................ 38 
4.3.1. ARV-471 ...................................................................................................... 38 
4.3.2. Anastrozole ................................................................................................... 39 
4.4. Safety Review Committee ......................................................................................... 39 
4.5. Start and End of Study Definition .............................................................................. 39 
5. STUDY POPULATION .................................................................................................. 39 
5.1. Inclusion Criteria ...................................................................................................... 40 
5.2. Exclusion Criteria ..................................................................................................... 41 
5.3. Lifestyle Considerations ............................................................................................ 43 
5.4. Screen Failures .......................................................................................................... 43 
5.4.1. Re-testing During Screening ......................................................................... 43 
6. STUDY INTERVENTION(S) AND CONCOMITANT THERAPY ................................ 43 
6.1. Study Intervention(s) Administered ........................................................................... 44 
6.1.1. Administration .............................................................................................. 44 
6.1.1.1. Arm A .......................................................................................... 44 
6.1.1.2. Arm B .......................................................................................... 45 
6.2. Preparation, Handling, Storage and Accountability.................................................... 45 
6.2.1. Preparation and Dispensing ........................................................................... 46 
6.2.2. Clinical Product Complaints .......................................................................... 46 
6.3. Assignment to Study Intervention ............................................................................. 46 
6.4. Study Intervention Compliance ................................................................................. 46 
6.5. Dose Modification and Treatment Discontinuation .................................................... 47 


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6.5.1. ARV-471 ...................................................................................................... 47 
6.5.2. Anastrozole ................................................................................................... 49 
6.6. Continued Access to Study Intervention After the End of the Study .......................... 49 
6.7. Treatment of Overdose .............................................................................................. 49 
6.8. Prior and Concomitant Therapy ................................................................................. 50 
6.8.1. Prohibited Therapy ........................................................................................ 50 
6.8.1.1. ARV-471 ..................................................................................... 50 
6.8.1.2. Anastrozole .................................................................................. 51 
6.8.1.3. Other Prohibited and/or Limited use of 
Anti-tumor/Anti-Cancer or Experimental Drugs, or Procedures ............ 51 
6.8.2. Other Restrictions and Precautions ................................................................ 51 
6.8.3. Supportive Care ............................................................................................ 51 
6.9. Surgical Resection..................................................................................................... 51 
7. DISCONTINUATION OF STUDY INTERVENTION AND PARTICIPANT 
DISCONTINUATION/WITHDRAWAL ........................................................................ 52 
7.1. Criteria for Stopping the Study .................................................................................. 52 
7.2. Discontinuation of Study Intervention ....................................................................... 52 
7.3. Participant Discontinuation/Withdrawal From the Study ........................................... 53 
7.3.1. Withdrawal of Consent.................................................................................. 54 
7.4. Lost to Follow-Up ..................................................................................................... 54 
8. STUDY ASSESSMENTS AND PROCEDURES ............................................................ 55 
8.1. Efficacy Assessments ................................................................................................ 56 
8.1.1. Disease Response Assessment ....................................................................... 56 
8.1.1.1. Imaging and Clinical Assessment ................................................. 56 


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8.1.1.2. Radiographic Imaging Assessment ............................................... 56 
8.1.1.3. Physical Exam: Caliper-based Measurements ............................... 56 
8.1.1.4. Local Pathological Assessment of Tissue from Surgical 
Resection ............................................................................................. 56 
8.2. Safety Assessments ................................................................................................... 57 
8.2.1. Physical Examinations .................................................................................. 57 
8.2.2. Vital Signs .................................................................................................... 57 
8.2.3. Electrocardiograms ....................................................................................... 58 
8.2.4. Clinical Safety Laboratory Assessments ........................................................ 58 
8.3. Adverse Events, Serious Adverse Events, and Other Safety Reporting ...................... 59 
8.3.1. Time Period and Frequency for Collecting AE and SAE Information ............ 59 
8.3.1.1. Reporting SAEs to Pfizer Safety ................................................... 60 
8.3.1.2. Recording Nonserious AEs and SAEs on the CRF ........................ 60 
8.3.2. Method of Detecting AEs and SAEs.............................................................. 61 
8.3.3. Follow-Up of AEs and SAEs......................................................................... 61 
8.3.4. Regulatory Reporting Requirements for SAEs .............................................. 61 
8.3.5. Environmental Exposure, Exposure During Pregnancy or Breastfeeding, 
and Occupational Exposure ................................................................................ 62 
8.3.5.1. Exposure During Pregnancy ......................................................... 62 
8.3.5.2. Exposure During Breastfeeding .................................................... 63 
8.3.5.3. Occupational Exposure ................................................................. 64 
8.3.6. Lack of Efficacy............................................................................................ 64 
8.3.7. Medication Errors ......................................................................................... 64 
8.4. Pharmacokinetics ...................................................................................................... 65 


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8.4.1. Collection of Samples ................................................................................... 65 
8.4.1.1. Determination of Drug Concentration ........................................... 65 
8.4.1.2. Determination of Pharmacokinetic of Individual Participants ....... 65 
8.5. Genetics .................................................................................................................... 65 
8.5.1. Specified Genetics ........................................................................................ 65 
8.6. Biomarkers................................................................................................................ 66 
8.6.1. Mandatory Tumor Biopsies ........................................................................... 66 
9. STATISTICAL CONSIDERATIONS ............................................................................. 66 
9.1. Statistical Hypotheses ............................................................................................... 66 
9.1.1. Multiplicity Adjustment ................................................................................ 66 
9.1.2. Estimands ..................................................................................................... 67 
9.1.2.1. Primary Estimands ....................................................................... 67 
9.1.2.2. Secondary Estimands ................................................................... 67 
9.2. Analysis Sets ............................................................................................................. 67 
9.3. Statistical Analyses ................................................................................................... 68 
9.3.1. General Considerations ................................................................................. 68 
9.3.2. Primary Safety/Efficacy Analyses ................................................................. 69 
9.3.3. Secondary Endpoint(s)/Estimands Analysis................................................... 69 
9.3.4. Tertiary/Exploratory Endpoint(s) .................................................................. 69 
9.3.5. Subgroup Analyses ....................................................................................... 69 
9.3.6. Other Safety Analyses ................................................................................... 70 
9.4. Sample Size Determination ....................................................................................... 70 
10. SUPPORTING DOCUMENTATION AND OPERATIONAL 
CONSIDERATIONS ...................................................................................................... 73 


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10.1. Appendix 1: Regulatory, Ethical, and Study Oversight Considerations .................... 73 
10.1.1. Regulatory and Ethical Considerations ........................................................ 73 
10.1.1.1. Reporting of Safety Issues and Serious Breaches of the 
Protocol or ICH GCP ........................................................................... 73 
10.1.2. Financial Disclosure .................................................................................... 74 
10.1.3. Informed Consent Process ........................................................................... 74 
10.1.4. Data Protection ........................................................................................... 75 
10.1.5. Committees Structure .................................................................................. 75 
10.1.6. Dissemination of Clinical Study Data .......................................................... 75 
10.1.7. Data Quality Assurance ............................................................................... 76 
10.1.8. Source Documents ...................................................................................... 77 
10.1.9. Study and Site Start and Closure ................................................................. 77 
10.1.10. Publication Policy ..................................................................................... 78 
10.1.11. Sponsor’s Qualified Medical Personnel ..................................................... 78 
10.2. Appendix 2: Clinical Laboratory Assessments ......................................................... 79 
10.3. Appendix 3: Adverse Events: Definitions and Procedures for Recording, 
Evaluating, Follow-Up, and Reporting ........................................................................ 81 
10.3.1. Definition of AE ......................................................................................... 81 
10.3.2. Definition of an SAE ................................................................................... 82 
10.3.3. Recording/Reporting and Follow-Up of AEs and/or SAEs During the 
Active Collection Period .................................................................................... 83 
10.3.4. Reporting of SAEs ...................................................................................... 86 
10.4. Appendix 4: Contraceptive and Barrier Guidance .................................................... 88 
10.5. Appendix 5: Genetics .............................................................................................. 89 
10.6. Appendix 6: Liver Safety: Suggested Actions and Follow-Up Assessments ............. 90 


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10.7. Appendix 7: ECG Findings of Potential Clinical Concern ....................................... 92 
10.8. Appendix 8: Prohibited Concomitant Medications That May Result in DDI ............ 94 
10.9. Appendix 9: Alternative Measures During Public Emergencies ............................... 96 
10.9.1. Eligibility .................................................................................................... 96 
10.9.2. Telehealth Visits ......................................................................................... 96 
10.9.3. Study Intervention ....................................................................................... 96 
10.9.4. Adverse Events and Serious Adverse Events ............................................... 97 
10.9.5. Treatment for COVID While on Study ........................................................ 97 
10.9.6. Guidance for COVID vaccine administration .............................................. 97 
10.9.6.1. For Participants Who Have Not Initiated Study Treatment.......... 97 
10.9.6.2. For Participants Already on Study Treatment and Beyond 
Cycle 1 ................................................................................................. 97 
10.10. Appendix 10: Eastern Cooperative Oncology Group Performance Status .............. 98 
10.11. Appendix 11: Radiological Imaging Assessment: modified RECIST 1.1 ............... 99 
10.11.1. Imaging Requirements .............................................................................. 99 
10.11.2. Modified RECIST 1.1 Disease Assessment ............................................. 100 
10.11.2.1. Measurable Lesions at Baseline .............................................. 100 
10.11.2.2. Nontarget Lesions at Baseline................................................. 100 
10.11.2.3. Normal Sites of Disease.......................................................... 100 
10.11.2.4. Recording Modified RECIST 1.1 Tumor Assessments ........... 101 
10.11.3. Disease Response Status at Each Imaging Assessment ............................ 102 
10.11.3.1. Target Disease Response Status .............................................. 103 
10.11.3.2. Nontarget Disease Response Status ........................................ 103 
10.11.3.3. New Lesions ........................................................................... 104 


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10.11.3.4. Overall Response at Each Imaging Assessment ...................... 104 
10.12. Appendix 12: Abbreviations ................................................................................ 106 
10.13. Appendix 13: Protocol Amendment History ........................................................ 110 
10.14. Appendix 14: Signature Pages ............................................................................. 111 
10.14.1. Sponsor Approval Page ........................................................................... 111 
10.14.2. Investigator Acknowledgment ................................................................. 112 
11. REFERENCES ............................................................................................................ 113 
 
 
 


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LIST OF TABLES 
Table 1 
Screening Activities .............................................................................. 22 
Table 2 
Schedule of On-Treatment Activities ..................................................... 23 
Table 3 
PK Sampling Schedule for Participants Receiving ARV-471 ................. 26 
Table 4 
Study Product Description ..................................................................... 44 
Table 5 
Study Treatment .................................................................................... 44 
Table 6 
Dose Reduction – Guidance for Adverse Events Related to ARV-
471 (Except QTcF Prolongation) ........................................................... 49 
Table 7 
Confidence Intervals for Mean Percentage of Baseline Value in Ki-
67 After Two Weeks ............................................................................. 71 
Table 8 
Confidence Intervals for the Ratio Between the Mean Percentage of 
Baseline Values for Ki-67 Observed from ARV-471 and 
Anastrozole Arms (Ki-67 Evaluable Participants N=120) ...................... 71 
Table 9 
Core Lab Tests ...................................................................................... 79 
Table 10 
RECIST 1.1 Modifications .................................................................... 99 
Table 11 
RECIST 1.1 Overall Response at Each Assessment ............................. 104 
Table 12 
Non-Target Disease Only RECIST 1.1 Overall Response at Each 
Assessment.......................................................................................... 105 
 
LIST OF FIGURES 
Figure 1 
ARV-471 Significantly Inhibits Tumor Growth and Reduces ER 
Levels in the MCF7 Xenograft Model ................................................... 30 
 
 
 


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DOCUMENT HISTORY 
Document 
Date of Issue 
Original protocol 
27 May 2022 
 Amendment to Original Protocol 
14 Dec 2022 
Global Amendment #1 
09 Jan 2023 
 
Protocol Amendment Summary of Key Changes Table 
Global Amendment #1 (09-JAN-2023) 
Overall Rationale for the Amendment: To align the protocol with the most current version 
of the Investigator’s Brochure, 
, add 
mRECIST, and further clarify some operational aspects of the study. 
Substantial Amendment: No 
Section # and Name 
Description of Key Changes 
Brief Rationale 
1.1 Synopsis and 
throughout 
Surgical resection accepted C6D18 
± 14 days instead of C6D18 ± 10 
days 
To allow the sites more flexibility in 
scheduling of surgery. 
1.1 Synopsis  
Inclusion clarified to participants 
for whom neoadjuvant endocrine 
monotherapy is deemed appropriate 
Study population further clarified  
 
 
1.1 Synopsis 
Addition to exclusion criteria #7 to 
exclude patients with rare 
hereditary problems of galactose 
intolerance, the Lapp lactase 
deficiency or glucose-galactose 
malabsorption. 
Included further detail on population 
of patients that should be excluded 
from study 
 
 
1.3 Schedule of 
Activities 
ECG may be performed on site or 
vendor machines 
To allow the sites to use the vendor 
ECG machine in screening if 
available.  
1.3 Schedule of 
Activities 
If screening ECG is used for C1D1, it 
must be done in triplicate and on a 
vendor machine 
Clarification of the process for 
substitution of screening for C1D1 ECGs 
at baseline. 
2.2.1.1.3 Nonclinical 
Pharmacokinetics and 
Drug-Drug 
Interactions 
Removed language that indicated PPIs 
are allowed and added details to 
Section 6.8.1.1 indicating that PPIs are 
not recommended. 
To align section with the most current 
version of the Investigator’s Brochure 
(version 4.0). 
2.2.1.2 Anastrozole 
Addition of suggestion for bone 
mineral density testing 
Added language regarding bone mineral 
density from the anastrozole SmPC  
 
 
4.3.1 ARV-471 
Additional information provided 
regarding suggested ARV-471 dose 
To align section with more current data 
to support dose selection. 


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Section # and Name 
Description of Key Changes 
Brief Rationale 
5.1 Inclusion Criteria 
Inclusion clarified to participants for 
whom neoadjuvant endocrine 
monotherapy is deemed appropriate  
Study population further clarified  
 
 
5.2 Exclusion Criteria  
Addition to exclusion criteria #7 to 
exclude patients with rare hereditary 
problems of galactose intolerance, the 
Lapp lactase deficiency or glucose-
galactose malabsorption.  
Included further detail on population of 
patients that should be excluded from 
study 
 
  
6 Study 
Intervention(s) and 
Concomitant Therapy 
Bulk bottle supply language removed 
from Table 4 
Bulk bottles will no longer be used in 
this study. 
6.1.1 Administration 
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. 
To allow patients to continue dosing 
study drug beyond C6D18 + 14 days 
after discussion with medical monitor. 
6.5.1 ARV-471 
Clarification in footnotes in Table 6 
that only one dose re-escalation is 
permitted. 
Clarification that only one dose re-
escalation of ARV-471 will be allowed. 
6.8 Prior and 
Concomitant Therapy 
Additional detail added regarding 
herbal supplements and concomitant 
medications. Herbal supplements are 
not recommended. Other concomitant 
medications may be considered on a 
case-by-case basis.  
Given potential for interactions with 
herbal supplements, language added 
indicating they are not recommended on 
study. 
6.8.1.1 ARV-471 
Details added regarding co-
administration of PPIs and H2 
blockers. The concomitant use of PPIs 
with ARV-471 is not recommended. 
H2 blockers (eg, cimetidine, 
famotidine) or local antacids (eg, 
aluminum hydroxide, calcium 
carbonate, bismuth subsalicylate) may 
be used.  
To align concomitant medications 
section with the most current version of 
the Investigator’s Brochure (version 4.0). 
6.8.1.3 Other 
Prohibited and/or 
Limited use of Anti-
tumor/Anti-Cancer or 
Experimental Drugs, 
or Procedures 
Clarification added for therapies with 
known anti-cancer effects  
Clarification that the on-study 
prohibition of anti-cancer therapies is 
limited to the time prior to surgical 
resection. 
6.8.2 Other 
Restrictions and 
Precautions 
Clarification added for participation in 
any other interventional or 
non-interventional studies 
To allow for prospective evaluation of 
participation in any other investigational 
study by medical monitor. 
8.1.1.2 Radiographic 
Imaging Assessment 
Added MRI as preferred imaging 
modality 
RECIST 1.1 guidelines specify that MRI 
is the preferred imaging modality to 
follow breast lesions in the neoadjuvant 
setting. 
8.1.1.2 Radiographic 
Imaging Assessment 
Modifications made to include 
modified RECIST 1.1 (see also 
Appendix 11) 
Clarification that mRECIST will be used 
to define response. 


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Section # and Name 
Description of Key Changes 
Brief Rationale 
8.2.3 
Electrocardiograms 
Clarification that if screening ECG is 
obtained on a vendor machine within 
96 hours of C1D1 in triplicates, there is 
no need to repeat the pre-dose ECG 
testing on C1D1. 
 
Details added regarding collection of 
ECGs. All triplicate ECG tracings will 
be sent electronically to a central ECG 
laboratory for manual interval 
measurements. All ECG’s must be 
reviewed by qualified personnel at 
the site. If vendor ECG machine 
readings return an abnormal ECG 
finding, the investigator may use 
their site machine to repeat the 
assessment.  
Clarification on the process for 
collecting ECGs and interactions with 
central ECG vendor. 
8.3.1 Time Period and 
Frequency for 
Collecting AE and 
SAE Information 
Addition of definition of last 
administration of study intervention as 
study drug treatment of surgical 
resection, whichever comes last. 
Clarify meaning of last administration of 
study intervention. 
8.3.1.2 Recording 
Nonserious AEs and 
SAEs on the CRF 
Clarification that the recording of non-
serious AEs and SAEs will continue 
until 30 days after last administration 
of study intervention. 
Clarification as to when recording of 
non-serious AEs and SAEs will stop. 
9.3.1 General 
Considerations 
Clarification that CIs will be two-sided. 
Stats clarification. 
9.3.3 Secondary 
Endpoint(s)/Estimands 
Analysis 
Clarification that radiographic response 
will be evaluated per mRECIST. 
To align evaluation with addition of 
Appendix 11. 
10.11 Appendix 11: 
Radiological Imaging 
Assessment: modified 
Requirements and 
RECIST 1.1 
Addition of Appendix 11 to describe 
modified RECIST 1.1 
Clarification on definition of mRECIST 
for this trial. 
 
 
 
 
 
 
 


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1. PROTOCOL SUMMARY  
1.1. Synopsis  
Name of Sponsor/Company: Arvinas Estrogen Receptor, Inc. (Arvinas) 
Name of Investigational Product(s): ARV-471 and anastrozole 
Title of Study: 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 
Study Centers: Multicenter, global [US, Germany, Georgia, and Spain] 
Phase of Development: Phase 2 
Objectives, Endpoints and Estimands: 
Objective  
Endpoints  
Primary  
Evaluate the effects of ARV-471 and 
anastrozole, respectively, on Ki-67 
expression in tumors after 2 weeks of 
treatment 
Percent change in Ki-67 expression between baseline 
and C1D15 tumor biopsies 
Estimand: See Section 9.1.2.1. 
Secondary  
Evaluate the safety and tolerability of 
ARV-471 and anastrozole, respectively 
Incidence of all adverse events, serious adverse events, 
and adverse events leading to study drug 
discontinuation  
Evaluate the clinical and pathological 
response of ARV-471 and anastrozole, 
respectively 
Pathologic stage, pathologic complete response (pCR) 
rate, and modified Pre-operative Endocrine Prognostic 
Index (mPEPI) score at the time of surgical resection 
(C6D18 ± 14 days); rates of breast conserving surgery 
(BCS); radiographic response of the primary tumor 
based on breast imaging during cycle 6; caliper-based 
response on C6D1  
Exploratory  
Evaluate the effects of ARV-471 and 
anastrozole, respectively, on CCCA after 2 
weeks of treatment  
CCCA (Ki-67 ≤2.7%) rates at C1D15 
Evaluate ER degradation by ARV-471  
Percent change in ER protein levels between baseline 
and C1D15 
Evaluate the effects of ARV-471 and 
anastrozole, respectively, on Ki-67, and 
ER degradation by ARV-471 in tumors at 
the time of surgical resection  
Changes in ER and Ki-67 expression between baseline 
and Cycle 6 surgical tumor samples; Rates of CCCA in 
the Cycle 6 surgical samples 
Explore additional biomarkers that may be 
associated with the effects of ARV-471 in 
tumor tissue  
Additional biomarkers may include, but are not limited 
to, PgR expression, 
 
 
Correlate exposure of ARV-471 with ER 
reduction  
Correlate population PK model-derived PK parameters 
(AUC, Cmin, Cmax) with ER reduction or other response 
parameters 


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Rationale/Overall Study Design: 
Clinical trials evaluating pre-operative endocrine therapy in hormone receptor positive 
(HR+) human epidermal growth factor receptor 2 negative (HER2–) breast cancer allow 
for rapid assessment of novel therapeutic approaches (Guerrero-Zotano 2017; Denduluri 
2018). Several trials evaluating pre-operative endocrine therapy have focused on biologic 
endpoints in tumor samples. In particular, Ki-67 has been used as a biomarker to assess the 
activity of ER-targeting agents, and Ki-67 results in the neoadjuvant setting may correlate 
with outcomes in the adjuvant or metastatic setting (Guerrero-Zotano 2017).  
 
This trial is a Phase 2 neoadjuvant study evaluating ARV-471 or anastrozole in 
post-menopausal women with ER+/HER2– localized breast cancer. ARV-471 is an orally 
bioavailable PROteolysis TArgeting Chimera (PROTAC®) small molecule that induces 
active degradation of the ER via recruitment of the cereblon E3 ligase. Anastrozole is an 
aromatase inhibitor (AI) that is commonly used (and considered SOC) in the neoadjuvant 
treatment of post-menopausal women with HR+ breast cancer.  
 
This trial will provide the first opportunity to evaluate the pharmacodynamic effects, 
safety, and activity of ARV-471 in a treatment-naïve setting. It will also allow evaluation 
of the PD activity (mainly via Ki-67) of ARV-471 or anastrozole in the treatment-naïve 
setting. These results will help inform future definitive studies in early and late-stage 
ER+/HER2– breast cancer.  
 
Overall Design: 
This is a Phase 2, open-label, randomized, non-comparative proof of concept study of 
ARV-471 or anastrozole in participants with ER+/HER2– breast cancer amenable to 
definitive surgical resection. The main goal of this study is to evaluate the biological 
activity of ARV-471 and anastrozole, respectively.  
 
Participants will be randomized in a 2:1 manner to receive treatment on one of two 
treatment arms for approximately 5.5 months:  
• Arm A: ARV-471 200 mg PO, daily and continuously until the day before surgical 
resection (no later than C6D18 + 14 days)  
• Arm B: anastrozole 1 mg PO, daily and continuously until the day before surgical 
resection (no later than C6D18 + 14 days)  
Stratification will occur based on the following features of the participant’s breast cancer: 
• Size of primary breast tumor (T-stage): ≤2 cm, >2 to <5 cm, or ≥5 cm. 
• Ki-67 score (assessed locally): <20% or ≥20% 
Participants will have a screening biopsy, an on-treatment biopsy on C1D15 (+5 days), and 
surgical resection approximately 5.5 months after starting treatment (C6D18 ± 14 days). 
Participants will return for follow up 30 days (+7 days) after definitive surgical resection. 
After surgery, participants will receive standard of care radiation and systemic therapy 
(chemotherapy, endocrine therapy, etc.) in accordance with local practice guidelines per 
the treating physician’s discretion. No participant should take study drug dispensed for the 


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trial after surgical resection, and no study drug should be dispensed after surgical 
resection. 
 
A Safety Review Committee will review all data from participants enrolled in this study. 
Number of Participants (Planned): 
Approximately 150 participants are expected to be enrolled (~100 participants in Arm A 
and 50 participants in Arm B). It is estimated that this sample size will provide 
approximately 120 (80 in Arm A and 40 in Arm B) participants with evaluable paired 
biopsies (screening and C1D15 biopsies). 
Diagnosis and Main Criteria for Eligibility: 
Participants must meet all of the inclusion and exclusion criteria specified in Section 5 of 
the protocol.  
 
Participants for whom neoadjuvant endocrine monotherapy is deemed appropriate are 
eligible for inclusion in this study only if all the following key inclusion criteria are met:  
 
Type of participant and target disease characteristics:  
• Post-menopausal females ≥18 years  
o Post-menopausal status will be defined by at least one of the following: prior 
bilateral oophorectomy, age ≥60, or age <60 and amenorrheic for at least 
12 months (in the absence of chemotherapy, tamoxifen, toremifene, ovarian 
suppression, or any additional medical intervention that may have induced 
amenorrhea) and follicle stimulating hormone/estradiol in the postmenopausal 
range  
• Histologically or cytologically confirmed ER+ and HER2– breast cancer (per local 
assessment). ER and HER2 status must be documented:  
o ER+ disease, with ER staining of ≥10% of tumor cell nuclei by IHC per 
ASCO/CAP Guidelines (Allison 2020).  
o HER2– disease by either IHC or in situ hybridization per ASCO/CAP 
guidelines  
o Ki-67 score ≥5%, analyzed locally 
• Clinical T1c-T4c, N0-N2, M0 breast cancer amenable to definitive surgical 
resection, without bilateral breast ductal carcinoma in situ or invasive breast cancer  
• The primary tumor must be at least 1.5 cm by imaging  
• ECOG performance status of 0 or 1  
• Willingness to undergo a screening biopsy, an on-treatment biopsy and surgical 
resection  
Laboratory Findings:  
• Adequate bone marrow function defined as follows (with no transfusion of blood 
products or use of hematopoietic growth factors in the 28 days prior to enrollment): 
• Absolute neutrophil count of ≥1500/mm3 or ≥1.5 × 109/L  


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• Platelets of ≥100,000/mm3 or ≥100 ×109/L  
• Hemoglobin ≥9 g/dL  
• aPTT ≤1.25 × ULN and INR ≤1.25  
• Unless the participant is receiving anticoagulation, then aPTT and INR should be 
within the therapeutic range of the intended use.  
• Adequate renal function defined as serum creatinine of ≤1.5 × ULN or an estimated 
creatinine clearance of ≥60 mL/min by Cockcroft Gault  
• Adequate liver function defined as:  
• Total serum bilirubin of ≤1.5 × ULN unless the participant has documented Gilbert 
syndrome. Participants with Gilbert syndrome must have total serum bilirubin 
≤3 × ULN.  
• AST and ALT of ≤2.5 × ULN 
Participants will not be eligible for this study if any of the following key exclusion criteria 
are met: 
Medical conditions:  
• Any other active malignancy within 3 years prior to enrollment, except for 
adequately treated basal cell or squamous cell skin cancer, or cervical carcinoma in 
situ  
• Any of the following in the previous 6 months:  
o Myocardial infarction  
o Severe unstable angina  
o Coronary/peripheral artery bypass graft  
o Symptomatic congestive heart failure (New York Heart Association class III or 
IV)  
o Cerebrovascular accident  
o Transient ischemic attack  
o Symptomatic pulmonary embolism or other clinically significant episode of 
thromboembolism 
• Any of the following in the previous 6 months:  
o Congenital long QT syndrome  
o Torsade de Pointes  
o Sustained ventricular tachyarrhythmia and ventricular fibrillation  
o Left anterior hemiblock (bifascicular block)  
o Ongoing cardiac dysrhythmias of NCI CTCAE ≥Grade 2  
o Atrial fibrillation of any grade (≥Grade 2 in the case of asymptomatic lone 
atrial fibrillation)  
• QTcF >470 msec  
• Active, uncontrolled bacterial, fungal or viral infection, including HBV, HCV, and 
HIV or AIDS-related illness 


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• Active inflammatory gastrointestinal disease, chronic diarrhea, known uncontrolled 
diverticular disease, or previous gastric resection or lap band surgery  
• Cirrhosis meeting criteria for Child Pugh B and C  
Prior/concomitant therapy:  
• Prior treatment for breast cancer including systemic therapy (eg, chemotherapy, 
hormonal therapy), radiation, surgery, or any investigational agents  
• Any live vaccines within 14 days of planned start of first dose of study drug.  
• Taking the following agents within 14 days of C1D1 unless otherwise specified:  
o Sensitive P-gp substrates or P-gp substrates with narrow therapeutic indices  
o Strong CYP3A4 inhibitors or inducers  
o Any medications with known QT risk, and/or are associated with a risk of 
Torsades de Pointes, within 7 days of C1D1  
• Major surgery (as defined by the Investigator) within four weeks of first dose of 
study drug  
Allergy and other drug reactions:  
• History of allergy or reaction to any of the drug components for ARV-471 or 
anastrozole, including patients with rare hereditary problems of galactose 
intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption. 
Other criteria:  
• Inability to take oral medication without crushing, dissolving, or chewing tablets  
Study Intervention, Dosage and Mode of Administration: 
ARV-471 will be dosed at 200 mg administered orally once a day, continuously 
throughout each 28-day cycle until the day before surgery (no later than 
C6D18 + 14 days). 
 
Anastrozole will be dosed at 1 mg administered orally once a day, continuously throughout 
each 28-day cycle until the day before surgery (no later than C6D18 + 14 days). 
Duration of Treatment: 
Planned Study Duration: Approximately 18 months (time from first participant enrolled 
until all participants have completed the study).  
Planned Treatment Duration: Participants will continue treatment with ARV-471 or 
anastrozole for approximately 5.5 months prior to undergoing surgical resection (no later 
than C6D18 + 14 days), and in the absence of disease progression that may jeopardize the 
opportunity for definitive surgery, unacceptable toxicity, participant withdrawal or 
Investigator’s decision or other criteria as defined in Section 7 of the protocol.  
Statistical Methods:  
Sample Size Determination  
This is a Phase 2 proof of concept study designed to generate data informing future studies 
about ARV-471. There are no plans for formal comparisons between ARV-471 and 
anastrozole. Descriptive statistics (including point estimates and two-sided confidence 
intervals) will be provided for all parameters of interest. Approximately 150 participants 
will be randomized to the two treatment arms in a 2:1 ratio (100 participants to the 
ARV-471 arm and 50 participants to the anastrozole arm). These numbers were chosen to 
provide meaningful information about the primary endpoint, ie, changes (on-treatment 


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C1D15 vs baseline) in Ki-67 expression levels after approximately 2 weeks of treatment 
with ARV-471 or anastrozole. Assume that 80% of the randomized participants will 
provide valid Ki-67 measurements from both their baseline and C1D15 biopsies. Also 
assume that Ki-67 will reduce to approximately 20 to 40% of their corresponding baseline 
values after 2 weeks of treatment. The width of the 80% CIs of the mean percentage Ki-67 
with ARV-471 will not exceed 14% and the width of the 95% CIs will not exceed 21.6%. 
The planned sample size will provide estimates for the treatment effect in terms of the 
reduction of Ki-67 with reasonable precision. 
  
Primary Safety/Efficacy Analyses  
Statistical analyses for the primary and secondary endpoints are summarized here. 
Additional analyses are described in Section 9 and in the SAP. 
  
Analyses for PD endpoints including the primary endpoint:  
Ki-67 expression will be assessed by immunohistochemical staining in a central 
laboratory.  
  
Analysis of Ki-67 reduction will be based on a Ki-67 evaluable population. The 
log-transformed percentage change in Ki-67 after approximately 2 weeks of treatment, ie, 
the ratio between the Ki-67 measurements obtained from C1D15 visit and baseline, will be 
modelled using a GLM, with both stratification factors (ie, baseline Ki-67 score and the 
tumor size) and treatment as covariates. Treatment effects for each arm will be 
summarized using the LSM and their two-sided confidence intervals on the log scale. In 
addition, for easier interpretation of the data, the treatment effects will be back transformed 
and expressed as the geometric means and their confidence intervals on the original 
percentage scale by treatment arm. Similar modeling will be applied to ER data. 
 
CCCA at week 2 is defined as Ki67 score ≤2.7%. An estimate of the difference in CCCA 
rates and corresponding 80% as well as 95% CIs will be calculated using Cochran 
Mantel-Haenszel methodology. Odds ratios between the treatment will be provided along 
with corresponding CIs. 
 
Analyses for clinical and pathologic response endpoints:  
pCR is defined as no invasive cancer in the breast and sampled axillary lymph nodes 
following completion of neoadjuvant systemic therapy. 
 
mPEPI score is derived from factors assigned a numerical score following neoadjuvant 
endocrine therapy, including Ki67 expression in the surgical specimen, pathologic tumor 
size and lymph node status. The proportion of participants achieving mPEPI score 0 after 
treatment will be evaluated. 
  
To support the secondary objective of evaluating clinical and pathologic response, binary 
or categorical endpoint such as pathologic stage, pCR, and participants with mPEPI score 
0 at the time of surgical resection (C6D18 ± 14 days), rates of breast conserving surgery, 
radiographic response per mRECIST in the primary tumor during cycle 6 will be 
summarized and estimated rate will be computed by treatment arm along with the exact CI 
using Wilson method; for caliper-based response on C6D1, best percentage change from 


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baseline will be graphed by treatment arm. All clinical and pathologic response will be 
listed for randomized participants by treatment arm.  
  
Safety analysis will be performed for all treated participants. Descriptive statistics of safety 
will be presented using NCI CTCAE v5.0. All TEAEs, drug-related AEs, SAEs and drug-
related SAEs will be tabulated using worst grade per NCI CTCAE v5.0 criteria by system 
organ class and MedDRA preferred term. On-study lab parameters including hematology, 
chemistry, liver function, and renal function will be summarized using worst grade per 
NCI CTCAE v5.0 criteria. The extent of exposure including number of doses, duration of 
treatment, and dose modifications will be summarized by treatment arm. A summary of 
deaths with reasons will be provided for all treated participants.  
 
 
 














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2. INTRODUCTION 
2.1. Study Rationale  
This is a Phase 2 neoadjuvant, non-comparative, POC study, evaluating ARV-471 or 
anastrozole in post-menopausal women with ER+/HER2– localized breast cancer. 
Clinical trials evaluating pre-operative endocrine therapy in ER+/HER2– breast cancer allow 
for rapid assessment of novel therapeutic approaches (Guerrero-Zotano 2017; 
Denduluri 2018). Pre-operative therapy can potentially downstage and improve suitability of 
breast conservation. Endocrine therapy is the therapeutic mainstay for ER+ breast cancer and 
targets ER activity and/or estrogen synthesis; however, many patients experience disease 
relapse or treatment resistance. Up to 20% of patients diagnosed with early-stage breast 
cancer relapse in the first 10 years, often with distant metastases (Johnston 2020). 
Several trials evaluating pre-operative endocrine therapy have focused on biologic activity 
endpoints in tumor samples (Ellis 2008; Smith 2005; Ellis 2011). Ki-67 has been used as 
biomarker to assess the activity of agents targeting the ER pathway. Several large trials 
demonstrate results in the neoadjuvant setting correlate to relapse free survival after 
definitive surgical resection (Smith 2020, Ellis 2008) and outcomes in the adjuvant or 
metastatic setting (Guerrero-Zotano 2017). For example, the improved Ki-67 suppression 
with AIs compared with tamoxifen in the neoadjuvant setting in the IMPACT and P024 trial 
(Ellis 2008, Smith 2005) parallels the improved disease-free survival seen with AIs in the 
adjuvant setting (The BIG 1-98 Collaborative Group 2005, Howell 2005). Furthermore, the 
similarity in Ki-67 suppression between nsAIs and sAIs in the neoadjuvant setting (Ellis 
2011) parallels the similar disease-free survival with these agents in the adjuvant setting 
(Goss 2013, Smith 2017). 
ARV-471 is an orally bioavailable PROteolysis TArgeting Chimera (PROTAC®) small 
molecule that induces active degradation of the ER via recruitment of the cereblon E3 ligase. 
In the ongoing FIH study, ARV-471 has demonstrated a tolerable safety profile, robust ER 
degradation, and preliminary evidence of clinical activity in participants with 
advanced/metastatic breast cancer who received prior CDK 4/6 inhibitors (Section 2.2.1.1.5; 
Hamilton 2022). Based on these data in combination with pre-surgical trials demonstrating 
SERDs have biological activity and a tolerable safety profile in early breast cancer 
(Lerebours 2016, Kuter 2012, Ma 2020, Hurvitz 2022a), ARV-471 is expected to be tolerable 
and lead to clinical responses in the neoadjuvant setting. 
This trial will provide the first opportunity to evaluate the biologic activity, clinical activity, 
and safety of ARV-471 in a treatment-naïve setting. 
Anastrozole is an AI that is commonly used in the neoadjuvant treatment of post-menopausal 
women with HR+ HER2– breast cancer both in clinical practice and in clinical trials 
(Ma 2020, Hurvitz 2020, Hurvitz 2022a). Anastrozole has also been approved for the 
treatment of HR+ breast cancer in the adjuvant and advanced/metastatic setting, and these 
results will help inform future definitive studies of ARV-471 in early- and late-stage 
ER+/HER2– breast cancer. 


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2.2. Background  
In 2020, there were 2.3 million women diagnosed with breast cancer and 685,000 deaths 
globally (Sung 2021). According to the World Health Organization, as of the end of 2020, 
there were 7.8 million women alive who were diagnosed with breast cancer in the past 5 
years, making it the world’s most prevalent cancer. HR+, defined as expression of ER and/or 
PgR, is the most common subtype encompassing approximately 80% of all breast cancers 
(Li 2020). 
Surgery is the cornerstone of treatment for early and locally advanced breast cancer and is 
often combined with radiation therapy and/or systemic anti-cancer therapy. In HR+ HER2– 
breast cancer, neoadjuvant chemotherapy is used as part of SOC to increase surgical options 
(eg, breast conservation) in patients with large tumors or lymph node involvement. Although 
the role of NET in this population is less clear, it may be used as part of SOC. NET provides 
a significantly less toxic alternative to chemotherapy that can lead to clinical responses in up 
to approximately 70% of patients (Ellis 2011). A meta-analysis comparing NET and 
neoadjuvant chemotherapy demonstrated no significant differences in the rates of clinical 
response and breast conservation (Spring 2016).  
In post-menopausal women with HR+ HER2– breast cancer, AIs have shown to have 
superior efficacy compared with tamoxifen. In the P024 neoadjuvant trial of postmenopausal 
women with HR+ invasive breast cancer not eligible for BCS, clinical ORR was 55% for 
women receiving letrozole vs 36% for those receiving tamoxifen (p<0.001) (Ellis 2008). The 
proportion of women able to undergo BCS at approximately 4 months was 45% in the 
letrozole group and 35% in the tamoxifen group (p=0.022) (Ellis 2008). In the PROACT trial 
of postmenopausal women with operable or potentially operable locally advanced HR+ 
breast cancer, clinical ORR was 49.7% for women who received anastrozole only and 39.7% 
for those who received tamoxifen only (odds ratio 1.50 [95% CI 0.96-2.34], p=0.08) 
(Cataliotti 2006). Forty three percent of women on anastrozole had improvement in feasible 
surgery at baseline to actual surgery as compared to 30.8% for tamoxifen (odds ratio 1.69 
[95% CI 1.01–2.81], p=0.04) (Cataliotti 2006). In the IMPACT trial of postmenopausal 
women with operable or potentially operable locally advanced ER+ breast cancer, the clinical 
ORR was 37% for women treated with anastrozole only, 36% for tamoxifen, and 39% for 
anastrozole and tamoxifen (Smith 2005). The odds ratio for ORR for anastrozole vs 
tamoxifen was 1.05 (95% CI 0.61-1.81, p=0.87) (Smith 2005). However, in women requiring 
mastectomy at baseline, 46% of women treated with anastrozole were deemed by a surgeon 
to be eligible for BCS as compared to 22% with tamoxifen (odds ratio 2.94; 
95% CI 1.11-7.81; p=0.03) (Smith 2005). Furthermore, a pooled analysis of 6 neoadjuvant 
trials of the 3rd generation AIs (anastrozole, letrozole, and vorozole) showed significant 
benefit of AIs over tamoxifen in clinical response rate (odds ratio 1.69, 95% CI 1.36-2.10; 
p<0.001), and radiographic response (odds ratio 1.49; 95% CI 1.18-1.89; p<0.001) 
(Spring 2016). In a pooled analysis of 4 trials of anastrozole and letrozole, AIs showed 
significant benefit over tamoxifen in radiographic response and BCS (odds ratio 1.62; 95% 
CI 1.24-2.12; p<0.001) (Spring 2016). 
Several trials have evaluated whether SERDs offer additional benefit compared to AIs in 
early breast cancer. Data generated on fulvestrant suggest similar Ki-67 reduction, clinical 


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response, and safety profile compared to AIs in in the pre-surgical setting (Lerebours 2016; 
Ma 2020; Quenel-Tueux 2015; Robertson 2013). Two novel oral SERDs have been 
evaluated in the pre-surgical setting: AZD9496 and giredestrant. In a WOO study, AZD-9496 
(no longer in clinical development) was tolerable but did not show improved Ki-67 reduction 
compared to fulvestrant, which may be attributable to suboptimal exposure 
(Robertson 2020). Giredestrant showed a tolerable safety profile and improved Ki-67 
reduction compared to anastrozole (reduction from baseline to Week 2 geometric 
mean=80%, 95% CI: −85% - −72% vs 67%, 95% CI: −75 - −56%; p=0.0222) 
(Hurvitz 2022a). 
2.2.1. Clinical Overview 
2.2.1.1. ARV-471 
ARV-471 is a potent, selective, orally bioavailable PROteolysis TArgeting Chimera 
(PROTAC®) small molecule that induces active degradation of the ER. ARV-471 is being 
developed for the treatment of patients with ER+/HER2– locally advanced or metastatic 
breast cancer. ARV-471 works by recruiting an E3 ligase to ubiquitinate ER; once 
ubiquitinated, ER is degraded into small peptides by the proteasome. 
The importance of ER degradation in HR+ metastatic breast cancer was established by the 
ER-targeted agent, fulvestrant. Fulvestrant has low oral bioavailability and is administered by 
intramuscular injection. In clinical trials, fulvestrant results in 40-60% degradation of ERs 
(Robertson 2013, Robertson 2001, Kuter 2012).  
ARV-471 is orally administered, and in nonclinical studies demonstrated potent (<1 nM) and 
robust (>90%) ER degradation, even in the presence of clinically relevant ER mutations 
(Y537S and D538G). ARV-471 may have potential advantages over fulvestrant and other 
orally available SERDs. While SERDs destabilize ER and indirectly lead to ER degradation, 
ARV-471 actively induces ER degradation, which may lead to less drug resistance. 
Furthermore, ARV-471 demonstrates superior tumor growth inhibition compared to 
fulvestrant in a Y537S ESR1 mutant patient-derived xenograft (ARV-471 IB). 
2.2.1.1.1. Mechanism of Action 
ARV-471 is a hetero-bifunctional PROTAC® molecule that simultaneously binds ER and the 
cereblon E3 ligase complex, enabling protein-protein interactions between ER and the ligase 
complex. As a result, ER becomes poly-ubiquitinated on accessible lysine residues and, 
subsequently, undergoes targeted degradation by the proteasome for elimination from cells. 
Several nonclinical studies have been conducted to confirm the mechanism of action for 
ARV-471 as described in the ARV-471 IB. A summary of the data is described below. 
In vitro data demonstrated a dose-dependent decrease in ER levels in 6 ER+ cell lines 
(MCF7, T47D, BT474, CAMA-1, ZR751, and 134-VI). Furthermore, data from MCF7 cell 
lines provide evidence that ARV-471 degrades ERs via the proteasome by hijacking an 
intracellular E3 ligase. In MCF7 cells treated with ARV-471, a half-maximal DC50 of 0.9 nM 
was achieved with maximum ER degradation of >90%. When excess cereblon ligand 
(lenalidomide) or proteasome inhibitor (carfilzomib) was added, no ER degradation was 
seen. In vitro data also demonstrated that ARV-471 decreased levels of clinically relevant 


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mutant forms of ER, Y537S and D538G, in a dose-dependent manner, similar to fulvestrant. 
In a T47D cell line background, GI50 values were 50 nM for ER Y537S and 8 nM for ER 
D538G. 
In addition to ARV-471, its epimer, ARV-473, was assessed for ER degradation activity 
(ARV471-00046-00-INVITRO). While both ARV-471 and fulvestrant reduced ER levels, 
ARV-473 did not reduce ER levels, even when tested at  μM. In an ER-dependent gene 
reporter assay (ARV471-00002-00-INVITRO), ARV-471 and ARV-473 had similar 
antagonist activity, indicating that ARV-471 has both antagonist and degradation activities 
against ER, whereas ARV-473 displays only antagonist activity. 
In vivo data for MCF7 xenograft mouse models demonstrated both potent ER degradation 
and tumor growth inhibition after administration of ARV-471 by oral gavage for 28 days 
(Figure 1). At study termination, all doses of ARV-471 (3 mg/kg, 10 mg/kg, and 30 mg/kg 
daily) significantly reduced ER levels by >94% compared to placebo. Dose-dependent TGI 
was also observed: 85% at 3 mg/kg/day, 98% at 10 mg/kg/day, and 125% at 30 mg/kg/day. 
Figure 1 
ARV-471 Significantly Inhibits Tumor Growth and Reduces ER Levels in 
the MCF7 Xenograft Model 
 
(A) Dose-dependent inhibition of tumor growth by ARV-471 in an orthotopic MCF7 mouse 
xenograft model. Female NOD/SCID mice were implanted with MCF7 cells in the mammary 
fat pad and ARV-471 administration (QD×28; PO) was initiated once the tumors reached 
200 mm3. Tumor volumes were evaluated twice per week for 28 days. ARV-471 at 3, 10, or 
30 mg/kg inhibited growth of estradiol-stimulated MCF7 xenografts (85%, 98%, and 124% 
TGI, respectively). (B) At study termination, MCF7 xenografts were harvested and the ER 
levels in the xenografts were measured by immunoblotting and normalized to β-actin levels. 
At all dose levels of ARV-471, >94% loss of ER was seen by immunoblot. 
Lastly, as described in Section 2.2.1.1.5, preliminary data from the FIH clinical trial 
ARV-471-mBC-101, demonstrates robust ER degradation in participants with wild type and 
mutant forms of ER. 


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2.2.1.1.2. Impact of Cereblon Substrates 
Since ARV-471 engages the E3 ligase cereblon at the same binding site as IMiDs such as 
thalidomide, lenalidomide, and pomalidomide, ARV-471 was evaluated for its degradation 
effect on known cereblon neo-morphic substrates. In one study, overnight incubation of 
Ramos cells with increasing concentrations of ARV-471 did not lead to degradation of 
Ikaros, Aiolos, CK1α, and GSPT1, whereas the control IMiDs with known neomorphic 
substrate degradation activity (lenalidomide and CC-885) decreased levels of these 
neo-substrates. In another study with a cell line that expresses Sall4, a recently identified 
cereblon neomorphic substrate (Donovan 2018), partial degradation of Sall4 was seen with 
ARV-471, whereas complete degradation of Sall4 was seen with the IMiD lenalidomide at 
the same concentration (1 µM). No evidence of ARV-471-mediated Sall4 degradation was 
observed in a different cell line. While the teratogenic effects of the thalidomide class have 
been linked to their Sall4-degradation activity, no significant adverse effects due to potential 
partial loss of Sall4 are expected in the patient population included in this trial since most 
adult tissues do not express Sall4 (Tatetsu 2016). 
2.2.1.1.3. Nonclinical Pharmacokinetics and Drug-Drug Interactions 
Nonclinical PK data are provided in the ARV-471 IB. A summary of the key data is 
presented below.  
The PK profile of ARV-471 in mouse, rat, dog, and monkey was characterized by a low to 
moderate clearance (13.8 to 33.8% of hepatic blood flow), extensive tissue distribution (2.1 
to 6.0 L/kg volume of distribution at steady state), short to moderate t1/2 (2.1 to 8.2 hr), and 
moderate to good oral bioavailability (27 to 65%). 
Dose-dependent increases in ARV-471 exposure were observed when ARV-471 was 
administered as an oral solution in the mouse (10, 30, 100 mg/kg), rat (30, 100, 300 mg/kg), 
dog (15, 45, 90 mg/kg), and monkey (1 and 3 mg/kg). 
 
 
 
 
  
Absorption: 
Combined in vitro data suggests that ARV-471 is unlikely to be a substrate of intestinal 
efflux transporters including P-gp and BCRP. A moderate to good extent of oral absorption 
was generally obtained when ARV-471 was dosed as a solution formulation in nonclinical 
species, despite its low solubility and apparently low permeability in these in vitro assays 
(ARV-471 IB). 
Preliminary DDI results from Study ARV-471-CPhm-103 indicated administration of PPI, 
esomeprazole, with ARV-471 did not affect the PK of ARV-471 when given with a moderate 
fat, moderate calories meal.  
Metabolism and Drug-Drug Interactions: 


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Impact of CYP inhibitors/inducers or drug transporters on ARV-471 
Study ARV-471-00063-00-INVITRO, a CYP reaction phenotyping study, was conducted 
consistent with current FDA guidance (FDA Guidance 2020). This study indicated CYP3A4 
as the principal isoform responsible for CYP metabolism of ARV-471 (accounting for 85%). 
Drugs that are inhibitors of CYP3A4 may increase the exposure of ARV-471, whereas drugs 
that are inducers of CYP3A4 may reduce the exposure of ARV-471. 
Available in vitro data suggest that ARV-471 is unlikely to be a substrate of P-gp, BCRP, 
OATP1B1, and OATP1B3. 
Impact of ARV-471 on CYP, BCRP, and P-gp substrates 
In vitro, ARV-471 (PF-07850327) is a reversible inhibitor of CYP2B6 with an IC50 of 
16.0 μM. Initial DDI risk assessment based on the FDA Guidance for Industry (FDA 2020) 
indicated the potential for ARV-471 to inhibit CYP2B6 at clinically relevant concentrations 
associated with the 500 mg QD dose. However, subsequent mechanistic static modeling, 
using bupropion as the probe CYP2B6 substrate drug, indicated a low potential for DDI due 
to ARV-471-mediated reversible inhibition of CYP2B6 at human exposures associated with 
the 500 mg QD dose. Consequently, patients enrolled in clinical trials will be allowed to 
receive sensitive CYP2B6 substrates or CYP2B6 substrates with narrow therapeutic indices. 
 
 
ARV-471 does not induce CYP1A2, 2B6, and 3A4 in vitro. 
Nonclinical data indicate the potential of ARV-471 to inhibit human BCRP. However, based 
on preliminary PK and clinical data (n=8 participants receiving rosuvastatin concomitantly 
with ARV-471 as described in the ARV-471 IB), participants enrolled in this study will be 
allowed to receive sensitive BCRP substrates or BCRP substrates with narrow therapeutic 
indices.  
Nonclinical data indicate the potential of ARV-471 to inhibit P-gp. A summary of restrictions 
on concomitant medications is provided in Section 6.8.1. 
Refer to the most current ARV-471 IB version for additional information on ARV-471 
metabolism and potential DDIs. 


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2.2.1.1.4. Nonclinical Safety and Toxicology 
Nonclinical toxicology data is provided in the ARV-471 IB. A few key points are 
summarized below.  
Results of hERG assays for ARV-471 were negative. The hERG IC50 and therapeutically 
relevant human Cmax values for ARV-471 (using 500 mg ARV-471 QD as a reference) are 
separated by at least 69-fold. 
The 7- and 28-day oral toxicity studies in rats and dogs have shown ARV-471 to be well 
tolerated after QD dosing up to 100 mg/kg/day in rats and 90 mg/kg/day in dogs. Across the 
studies, there were no consistent findings or patterns of effects in hematology or clinical 
chemistry. As tested in dogs, ARV-471 did not elicit any changes in ECG evaluations after 
daily dosing at 90 mg/kg/day for 28 days. 
 
 
As expected, ARV-471 had effects on the reproductive systems of both female and male 
animals and showed recovery or evidence of reversibility following discontinuation of 
dosing. Findings in male and female animals were consistent with the pharmacological action 
of ARV-471 at the ER and have been observed in other agents that target the ER (eg, 
fulvestrant) (US FDA Fulvestrant 2002).  
 
 
 
 
 
 
 
2.2.1.1.5. Clinical Trial Data: Study ARV-471-mBC-101 
Study ARV-471-mBC-101 is an ongoing FIH Phase 1/2 open-label, dose-escalation, and 
cohort expansion clinical trial of ARV-471 given alone or in combination with palbociclib 
(IBRANCE®) in participants with ER+/HER2– locally advanced or metastatic breast cancer. 
Preliminary analyses completed on participants in the monotherapy dose escalation portion 
(Part A) of the FIH study suggest a tolerable safety profile, robust pharmacodynamic activity 
(ER degradation), and evidence of early clinical activity in participants who received prior 
CDK 4/6 inhibitor therapy. 
A summary of the findings from the monotherapy dose escalation and expansion can be 
found in the most current ARV-471 IB version. 


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2.2.1.2. Anastrozole 
In postmenopausal women, estrogens are mainly derived from the action of the aromatase 
enzyme, which converts adrenal androgens (primarily androstenedione and testosterone) to 
estrone and estradiol. The suppression of estrogen biosynthesis in peripheral tissues and in 
the cancer tissue itself can therefore be achieved by specifically inhibiting the aromatase 
enzyme (Anastrozole USPI).  
Anastrozole is a selective nsAI. It significantly lowers serum estradiol concentrations and has 
no detectable effect on formation of adrenal corticosteroids or aldosterone (Anastrozole 
USPI). 
In the US, anastrozole is currently indicated for adjuvant treatment of postmenopausal 
women with hormone receptor-positive early breast cancer and first-line treatment of 
postmenopausal women with hormone receptor-positive or hormone receptor unknown 
locally advanced or metastatic breast cancer. It is also indicated for the treatment of advanced 
breast cancer in postmenopausal women with disease progression following tamoxifen 
therapy. Patients with ER-negative disease and patients who did not respond to previous 
tamoxifen therapy rarely responded to anastrozole (Anastrozole USPI).  
In the EU, anastrozole is indicated for treatment of hormone receptor-positive advanced 
breast cancer in postmenopausal women and adjuvant (add-on) treatment of hormone 
receptor-positive early invasive breast cancer in postmenopausal women, including those 
who have received two to three years of adjuvant tamoxifen (Anastrozole European 
Medicines Agency Committee for Medicinal Products for Human Use SmPC). 
The dose of anastrozole is 1 mg tablet taken once a day (Anastrozole USPI). 
Anastrozole is contraindicated in pregnant and premenopausal women. It is also 
contraindicated in any patient who has shown a hypersensitivity reaction to the drug or any 
of the excipients (Anastrozole USPI). Additionally in the EU, it is specifically 
contraindicated in women who are breast feeding (Anastrozole European Medicines Agency 
Committee for Medicinal Products for Human Use SmPC). 
Serious adverse reactions with anastrozole occurring in less than 1 in 10,000 patients, are: 
1) skin reactions such as lesions, ulcers, or blisters; 2) allergic reactions with swelling of the 
face, lips, tongue, and/or throat. This may cause difficulty in swallowing and/or breathing; 
and 3) changes in blood tests of the liver function, including inflammation of the liver with 
symptoms that may include a general feeling of not being well, with or without jaundice, 
liver pain or liver swelling (Anastrozole USPI). 
Common adverse reactions (occurring with an incidence of >10%) in women taking 
anastrozole included: hot flashes, asthenia, arthritis, pain, arthralgia, pharyngitis, 
hypertension, depression, nausea and vomiting, rash, osteoporosis, fractures, back pain, 
insomnia, pain, headache, bone pain, peripheral edema, increased cough, dyspnea, 
pharyngitis, and lymphedema (Anastrozole USPI). 


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In the ATAC trial, the most common reported adverse reaction (>0.1%) leading to 
discontinuation of therapy for both treatment groups was hot flashes, although there were 
fewer patients who discontinued therapy as a result of hot flashes in the anastrozole group 
(Anastrozole USPI). 
As anastrozole lowers circulating estrogen levels it may cause a reduction in bone mineral 
density with a possible consequent increased risk of fracture. Women with osteoporosis or at 
risk of osteoporosis, should have their bone mineral density assessed as per investigator’s 
best medical judgement and based on local practice guidelines. Treatment or prophylaxis for 
osteoporosis may be initiated as appropriate and carefully monitored as per investigator’s 
judgement.  
Additional or updated information on anastrozole can be found in the most recent local 
product label.  
2.3. Benefit/Risk Assessment 
The main goals of this neoadjuvant study are to assess the biologic effects and safety of 
ARV-471 and anastrozole, respectively, in participants with early localized breast cancer. 
The study will enroll post-menopausal women with treatment naïve, ER+/HER2– breast 
cancer, amenable to definitive surgical resection, and randomize them to pre-operative 
treatment with ARV-471 or anastrozole. To allow participants the opportunity for clinical 
response, treatment will continue for approximately 5.5 months prior to surgical resection.  
NET has therapeutic potential for patients with ER+ breast cancer and is currently used as 
SOC in select patients, such as post-menopausal women, or those with ER+ tumors 
(Korde 2021; Gradishar 2021) to increase the likelihood of breast conservation. It provides a 
significantly less toxic alternative to chemotherapy that can lead to clinical responses that are 
comparable to neoadjuvant chemotherapy (Spring 2016; Wang 2020). Although tamoxifen 
and AIs are commonly used (Section 4.2.2), an optimal NET regimen has yet to be 
determined. In the neoadjuvant setting, selective ER downregulators and degraders and nsAIs 
demonstrate similar safety profiles, clinical response rates, breast conservation rates, and 
Ki-67 reduction (Lerebours 2016; Ma 2020; Quenel-Tueux 2015; Robertson 2013; Hurvitz 
2020). 
Preliminary data from the ongoing FIH study with ARV-471 has shown that ARV-471 has a 
tolerable safety profile, leads to robust ER degradation (including in participants with ESR1 
mutations), and results in clinical benefit that exceeds that of fulvestrant in participants 
previously treated with CDK 4/6 inhibitors (Hamilton 2022; Hurvitz 2022b; ARV-471 IB). 
Therefore, ARV-471 is expected to be tolerable and lead to clinical responses in the 
neoadjuvant setting. 
2.3.1. Risk Assessment 
In the ongoing FIH study, ARV-471 monotherapy Part A 30 to 700mg daily and Part B 200 
and 500 mg is well tolerated. No DLTs were observed and MTD was not reached. Most 
TRAEs were grade 1 or 2. The most common TRAEs observed in ≥10% of patients treated 


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with ARV-471 (monotherapy therapy Parts A and B) were fatigue, nausea, arthralgia, and hot 
flush. There were no dose dependent increases in treatment related AEs. 
More detailed information about the known and expected benefits and risks and reasonably 
expected AEs of ARV-471 may be found in the most current ARV-471 IB version, which is 
the SRSD for this study. For anastrozole, the SRSD is the anastrozole SmPC. 
Participant safety will be monitored closely throughout study participation (Appendix 3). The 
Sponsor will immediately notify the Principal Investigator if any additional safety or 
toxicology information becomes available during the study. 
3. OBJECTIVES, ENDPOINTS, AND ESTIMANDS 
Objective  
Endpoints  
Primary  
Evaluate the effects of ARV-471 and 
anastrozole, respectively, on Ki-67 
expression in tumors after 2 weeks of 
treatment 
Percent change in Ki-67 expression between baseline 
and C1D15 tumor biopsies 
Estimand: See Section 9.1.2.1. 
Secondary  
Evaluate the safety and tolerability of 
ARV-471 and anastrozole, respectively 
Incidence of all adverse events, serious adverse events, 
and adverse events leading to study drug 
discontinuation  
Evaluate the clinical and pathological 
response of ARV-471 and anastrozole, 
respectively 
Pathologic stage, pathologic complete response (pCR) 
rate, and modified Pre-operative Endocrine Prognostic 
Index (mPEPI) score at the time of surgical resection 
(C6D18 ± 14 days); rates of breast conserving therapy; 
radiographic response of the primary tumor based on 
imaging during cycle 6; caliper-based response on 
C6D1  
Exploratory  
Evaluate the effects of ARV-471 and 
anastrozole, respectively, on CCCA after 2 
weeks of treatment  
CCCA (Ki67 ≤2.7%) rates at C1D15  
Evaluate ER degradation of ARV-471  
Percent change in ER protein levels between baseline 
and C1D15   
Evaluate the effects of ARV-471 and 
anastrozole, respectively, on Ki-67, and ER 
degradation by ARV-471 in tumors at the 
time of surgical resection. 
Changes in ER and Ki-67 expression between baseline 
and Cycle 6 surgical tumor samples; Rates of CCCA in 
the Cycle 6 surgical samples.  
Explore additional biomarkers that may be 
associated with the effects of ARV-471 in 
tumor tissue  
Additional biomarkers may include, but are not limited 
to, PgR expression, 
 
  
Correlate exposure of ARV-471 with ER 
reduction  
Correlate population PK model-derived PK parameters 
(AUC, Cmin, Cmax) with ER reduction or other response 
parameters 


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4. STUDY DESIGN 
4.1. Overall Design 
This is a Phase 2, open-label, randomized, non-comparative POC study of ARV-471 or 
anastrozole in participants with ER+/HER2– breast cancer amenable to definitive surgical 
resection. The main goal of this study is to evaluate the biological activity of ARV-471 and 
anastrozole, respectively.  
Participants will be randomized in a 2:1 manner to receive treatment on one of two treatment 
arms for approximately 5.5 months:  
• Arm A: ARV-471 200 mg orally, daily, and continuously until day before surgical 
resection (no later than C6D18 + 14 days)  
• Arm B: anastrozole 1 mg orally, daily, and continuously until day before surgical 
resection (no later than C6D18 + 14 days) 
Stratification will occur based on the following features of the participant’s breast cancer: 
• Size of primary breast tumor (T-stage): ≤2 cm, >2 to <5 cm, or ≥5 cm. 
• Ki-67 score (assessed locally): <20% or ≥20% 
Participants will have a screening biopsy, an on-treatment biopsy on C1D15 (+5 days), and 
surgical resection approximately 5.5 months after starting treatment (C6D18 ± 14 days). 
Participants will return for follow up 30 days (+7 days) after definitive surgical resection. 
After surgery, participants will receive SOC radiation and systemic therapy (chemotherapy, 
endocrine therapy, etc.) in accordance with local practice guidelines per the treating 
physician’s discretion. No participant should take study drug dispensed for the trial after 
surgical resection, and no study drug should be dispensed after surgical resection. 
Approximately 150 participants are expected to be enrolled (~100 participants in Arm A and 
50 participants in Arm B). It is estimated that this sample size will provide approximately 
120 (80 participants in Arm A and 40 participants in Arm B) participants with evaluable 
paired biopsies (screening and C1D15 biopsies) as described Section 8.6.1. 
4.2. Scientific Rationale for Study Design 
4.2.1. Rationale for Selection of Patient Population 
This trial will enroll post-menopausal women with newly diagnosed and treatment naive 
ER+/HER2– breast cancer that is amenable to definitive surgical resection. Patients with 
HER2 over–expressing tumors are excluded as these patients receive SOC treatments that 
include HER2-targeted agents. This population selected includes participants that are 
typically considered for NET. Participants must also have tumor that is at least 1.5 cm as 
confirmed by imaging due to biopsy requirements for this study. 
4.2.2. Rationale for Selection of Control Arm 
In ER+/HER2– breast cancer, an optimal endocrine-based neoadjuvant regimen has yet to be 
established. AIs have been shown to have superior clinical activity to tamoxifen in 


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post-menopausal women (Section 2.2). NsAIs (anastrozole, letrozole) and sAIs (exemestane) 
have similar safety profiles and have shown similar efficacy in the neoadjuvant setting. The 
Z1031 study compared anastrozole, letrozole, and exemestane as NET in post-menopausal 
women with Stage II-III HR+ breast cancer and found all treatments to be similar 
(Ellis 2011). The clinical response rates for anastrozole, letrozole, and exemestane were 
69.1% (95% CI, 60.1% to 77.1%), 74.8% (95% CI, 66.3% to 82.1%), and 62.9% (95% CI, 
53.8% to 71.4%), respectively (Ellis 2011). At surgery at approximately 16 weeks, the 
geometric change in Ki-67 was -78% (standard error of the mean 4%) for 
anastrozole, -81.2% (standard error of the mean 3.5%) for exemestane, and -87.1% (standard 
error of the mean 2.8%) for letrozole (Ellis 2011). There was no significant difference in 
Ki-67 suppression between treatment arms (Kruskal-Wallis p=0.45, adjusted for three-way 
comparison) (Ellis 2011). 
Anastrozole has been used as a control arm for several recent neoadjuvant studies in breast 
cancer including the ALTERNATE, NeoMONARCH, and coopERA clinical trials. In 
randomized Phase 2 and 3 neoadjuvant trials, clinical objective response rates for patients 
receiving anastrozole monotherapy have ranged from 37% to 69.1% at surgery at 3 to 
6 months (Smith 2005; Cataliotti 2006; Lerebours 2016; Quenel-Tueux 2015; Ellis 2011). In 
these trials, the rates of BCS for patients receiving anastrozole ranged from 43% to 57.8% 
(Smith 2005; Cataliotti 2006; Lerebours 2016; Ellis 2011). Anastrozole has also been used in 
trials assessing Ki-67 including the Z1031, IMPACT, NeoMONARCH, and coopERA 
clinical trials. In these 4 trials of postmenopausal women with early or locally advanced HR+ 
breast cancer, Ki-67 reduction (geometric mean change) at 2 weeks ranged from -63% (90% 
CI, −73 to −49) to -76% (95% CI -81.9 to -68.2) for patients receiving anastrozole 
(Dowsett 2005; Smith 2005; Ellis 2011; Hurvitz 2020; Hurvitz 2022a). Given the clinical 
activity of anastrozole in the neoadjuvant setting and thus common usage as a SOC and 
control arm, it was chosen as the control arm for this study. 
4.2.3. Rationale for Duration of Treatment 
All participants will be treated with NET for approximately 5.5 months prior to definitive 
surgical resection. It takes a few months to achieve clinical responses or tumor shrinkage 
from NET, however the optimum duration of NET remains unclear. Four to six month 
treatment windows have been used by several NET trials in ER+/HER2– breast cancer 
(Guerrero-Zotano 2017; Barchiesi 2020; Martí 2021). 
4.2.4. Collection of Retained Research Samples  
Retained research samples will be collected and stored for further analyses which may, for 
example, provide greater understanding of the study intervention. 
4.3. Justification for Dose 
4.3.1. ARV-471 
In the FIH monotherapy dose escalation study, ARV-471-mBC-101, no DLTs were 
observed, and an MTD was not reached. The MAD was 700 mg (administered at 400 mg in 
the morning and 300 mg in the evening in 3 of the 4 participants to lessen pill burden). Two 
RP2Ds, 200 mg daily and 500 mg daily, were selected for Phase 2 evaluation in the ongoing 


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monotherapy expansion of ARV-471-mBC-101 to support dose selection for Phase 3 
evaluation of ARV-471 in metastatic breast cancer. Both doses resulted in steady state Cmax 
and AUC24 values that significantly exceeded thresholds associated with tumor regression in 
nonclinical models, eg, MCF7-tumor bearing NOD/SCID mice treated at 30 mg/kg. Both 
doses are also below the NOAEL of 100 mg/kg/day in female rats (the most sensitive species 
in nonclinical toxicology studies), which is equivalent to a human dose of approximately 
960 mg daily. Additionally, both doses had an acceptable safety profile, and ER degradation 
was demonstrated in participants across all doses in which paired biopsies were obtained. 
In Part B monotherapy expansion, no meaningful differences were noted between the 200 mg 
and 500 mg dose levels in overall safety, such as TRAEs, TEAEs leading to discontinuations, 
or dose interruptions (Hurvitz 2022b). Clinical benefit (as measured by CBR) was seen at 
both doses with no clear differences observed between the 200mg and 500mg dose levels. No 
significant dose-response relationship was seen between the 200 mg and 500 mg daily doses 
in a heavily pretreated population. 
Considering the benefits and risks in this early stage curable population, a 200-mg dose of 
ARV-471 was selected for this study based on the totality of safety, PK, PD, and efficacy 
data available from Part A dose escalation and backfill and Part B expansion of the FIH study 
as of 06 June 2022 (Hurvitz 2022b; ARV-471 IB). 
4.3.2. Anastrozole 
The approved dose and schedule of anastrozole will be used per the USPI (or local label). 
4.4. Safety Review Committee 
The SRC will review all data from participants enrolled in this study. The SRC will be 
responsible for making recommendations as to whether it is scientifically and ethically 
appropriate to continue enrollment, discontinue treatment groups, or stop the study. 
The SRC membership, will be comprised of selected study principal investigators and 
Sponsor representative(s). The SRC is responsible for reviewing and evaluating data at least 
every three months. 
4.5. Start and End of Study Definition 
The start of the trial is defined as the first participant’s first visit. End of study is defined as 
the last participant’s last study visit or follow-up phone call. Study completion is defined as 
the final date on which data for the primary endpoint was or is expected to be collected, if 
this is not the same. 
5. STUDY POPULATION 
This study can fulfill its objectives only if appropriate participants are enrolled. The 
following eligibility criteria are designed to select participants for whom participation in the 
study is considered appropriate. All relevant medical and nonmedical conditions should be 
taken into consideration when deciding whether a particular participant is suitable for this 
protocol.  


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Prospective approval of protocol deviations to recruitment and enrollment criteria, also 
known as protocol waivers or exemptions, is not permitted. 
5.1. Inclusion Criteria 
Participants for whom neoadjuvant endocrine monotherapy is deemed appropriate are 
eligible to be included in the study only if all of the following criteria apply:  
Age and Sex: 
1. Post-menopausal females ≥18 years 
• Post-menopausal status will be defined by at least one of the following: prior 
bilateral oophorectomy, age ≥60, or age <60 and amenorrheic for at least 
12 months (in the absence of chemotherapy, tamoxifen, toremifene, ovarian 
suppression, or any additional medical intervention that may have induced 
amenorrhea) and FSH/estradiol in the postmenopausal range  
Type of Participant and Disease Characteristics: 
2. Histologically or cytologically confirmed ER+ and HER2– breast cancer (per local 
assessment). ER and HER2 status must be documented: 
• ER+ disease, with ER staining of ≥10% of tumor cell nuclei by IHC per 
ASCO/CAP Guidelines (Allison 2020).  
• HER2– disease by either IHC or in situ hybridization per ASCO/CAP guidelines 
• Ki 67 score ≥5%, analyzed locally 
3. Clinical T1c-T4c, N0-N2, M0 breast cancer amenable to definitive surgical resection, 
without bilateral breast ductal carcinoma in situ or invasive breast cancer  
4. The primary tumor must be at least 1.5 cm by imaging 
5. Willingness to undergo a screening biopsy, an on-treatment biopsy and surgical 
resection 
Informed Consent:  
6. Capable of giving signed informed consent as described in Appendix 1, which 
includes compliance with the requirements and restrictions listed in the informed 
consent and in this protocol. 
Other Inclusion Criteria:  
7. ECOG PS 0 or 1. 
8. Adequate Bone Marrow Function, defined as (with no transfusion of blood products 
or use of hematopoietic growth factors in the 28 days prior to enrollment): 
• ANC ≥1,500/mm3 or 1.5 × 109/L; 
• Platelets ≥100,000/mm3 or 100 × 109/L; 


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• Hemoglobin ≥9 g/dL. 
9. aPTT ≤1.25 × ULN and INR ≤1.25 
• Unless the participant is receiving anticoagulation, then aPTT and INR should be 
within the therapeutic range of the intended use. 
10. Adequate renal function defined as serum creatinine of ≤1.5 × ULN or an estimated 
creatinine clearance of ≥60 mL/min by Cockcroft Gault 
11. Adequate liver function, defined as: 
• Total serum bilirubin of ≤1.5 × ULN unless the participant has documented 
Gilbert syndrome. Participants with Gilbert syndrome must have total serum 
bilirubin ≤3 × ULN. 
• AST and ALT of ≤2.5 × ULN  
12. Participants who are willing and able to comply with all scheduled visits, treatment 
plan, laboratory tests, lifestyle considerations, and other study procedures.  
5.2. Exclusion Criteria 
Participants are excluded from the study if any of the following criteria apply: 
Medical Conditions: 
1. Any other active malignancy within 3 years prior to enrollment, except for adequately 
treated basal cell or squamous cell skin cancer, or cervical carcinoma in situ. 
2. Any of the following in the previous 6 months:  
• Myocardial infarction  
• Severe unstable angina  
• Coronary/peripheral artery bypass graft  
• Symptomatic congestive heart failure (New York Heart Association class III or 
IV)  
• Cerebrovascular accident  
• Transient ischemic attack  
• Symptomatic pulmonary embolism or other clinically significant episode of 
thromboembolism 
3. Any of the following in the previous 6 months:  
• Congenital long QT syndrome  
• Torsade de Pointes  
• Sustained ventricular tachyarrhythmia and ventricular fibrillation  
• Left anterior hemiblock (bifascicular block)  
• Ongoing cardiac dysrhythmias of NCI Common CTCAE ≥Grade 2  
• Atrial fibrillation of any grade (≥Grade 2 in the case of asymptomatic lone atrial 
fibrillation) 


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4. Active inflammatory GI disease, chronic diarrhea, known uncontrolled diverticular 
disease or previous gastric resection or lap band surgery. 
5. Cirrhosis meeting criteria for Child Pugh B and C 
6. Major surgery (as defined by the Investigator) within four weeks of first dose of study 
drug  
7. History of allergy or reaction to any of the drug components for ARV-471 or 
anastrozole, including patients with rare hereditary problems of galactose intolerance, 
the Lapp lactase deficiency or glucose-galactose malabsorption. 
8. Inability to take oral medication without crushing, dissolving, or chewing tablets 
9. Other medical or psychiatric condition including recent (within the past year) or 
active suicidal ideation/behavior or laboratory abnormality that may increase the risk 
of study participation or, in the investigator’s judgment, make the participant 
inappropriate for the study. 
Prior/Concomitant Therapy: 
10. Prior treatment for breast cancer including systemic therapy (eg, chemotherapy, 
hormonal therapy), radiation, surgery, or any investigational agents.  
11. Any live vaccines within 14 days of planned start of first dose of study drug.  
12. Taking the following agents within 14 days of C1D1 unless otherwise specified:  
• Sensitive P-gp substrates or P-gp substrates with narrow therapeutic indices  
• Strong CYP3A4 inhibitors or inducers  
• Any medications with known QT risk, and/or are associated with a risk of 
Torsades de Pointes, within 7 days of C1D1  
Diagnostic Assessments: 
13. QTcF >470 msec 
14. Participants with active, uncontrolled bacterial, fungal, or viral infection, including 
(but not limited to) HBV, HCV, and known HIV or AIDS-related illness. 
Other Exclusions: 
15. Participants who are involuntarily incarcerated. (Note: under certain specific 
circumstances a person who has been imprisoned may be included or permitted to 
continue as a participant. Strict conditions apply and Sponsor approval is required.) 
16. Participants who are compulsorily detained for treatment of either a psychiatric or 
physical (eg, infectious disease) illness. 
17. Investigator site staff or Sponsor employees directly involved in the conduct of the 
study, site staff otherwise supervised by the investigator, and their respective family 
members. 


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5.3. Lifestyle Considerations 
Restrictions regarding lifestyle, activities, and/or diet required for study eligibility and/or 
participation are listed below. Participants will be instructed by the study staff on the 
following: 
• ARV-471 should be taken together with food at approximately the same time in the 
morning. Additional instructions on how to take ARV-471 is described in Section 6.1.  
• Participants should not consume grapefruit juice as it may interact with ARV-471. 
5.4. Screen Failures 
Screen failures are defined as participants who consent to participate in the clinical study but 
are not subsequently enrolled. A minimal set of screen failure information is required to 
ensure transparent reporting of screen failure participants, to meet the CONSORT publishing 
requirements, and to respond to queries from regulatory authorities. Minimal information 
includes date of consent, demography, screen failure details, eligibility criteria, and any AEs 
and SAEs. 
Individuals who do not meet the criteria for participation in this study (screen failures) must 
be indicated as such in the IRT system. 
Individuals who do not meet the criteria for participation in this study (screen failure) may be 
rescreened up to 2 times. 
5.4.1. Re-testing During Screening 
Re-testing of laboratory parameters and/or other assessments within the Screening period 
will be permitted (in addition to any parameters that require a confirmatory value). 
The most current result prior to enrollment is the value by which study inclusion will be 
assessed, as it represents the participant’s most current clinical state. 
6. STUDY INTERVENTION(S) AND CONCOMITANT THERAPY 
Study intervention is defined as any investigational intervention(s), marketed product(s), 
placebo, medical device(s), or study procedure(s) intended to be administered to a study 
participant according to the study protocol. 
For the purposes of this protocol, study intervention refers to ARV-471 and anastrozole. 
Other medications used as support or escape medication for preventative, diagnostic, or 
therapeutic reasons, as components of the SOC for a given diagnosis, may be considered as 
non-IPs. 


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Table 4 
Study Product Description  
Product 
Description/
Class and 
Dosage 
Form 
Potency 
IP/ 
Non-IP 
Appearance 
Packaging and 
Labelling 
Storage Conditions 
(per label) 
ARV-471 
tablets 
100 mg 
IP 
White to 
off-white 
oval tablet 
IP will be 
provided in a 
high-density 
polyethylene 
bottle with child-
resistant cap. 
Each bottle will 
be labelled as 
required per 
local regulations. 
ARV-471 Patient Bottle Supply 
(30 count): 
Store unopened bottle at 2°C to 
8°C (36°F to 47°F). Once a bottle 
is opened, it may be stored at 
temperatures up to 25°C (77°F) 
for 8 weeks. Protect from light. 
Anastrozole 
tablets  
1 mg 
IP 
See Pharmacy Manual for full description and Section 6.2 
The label text of the study treatments will comply with Good Manufacturing Practices and national legislation to meet 
requirements of the participating sites/countries. 
6.1. Study Intervention(s) Administered 
6.1.1. Administration 
Participants will be randomized to one of two treatment arms and will receive study drug for 
approximately 5.5 months prior to undergoing surgical resection (Table 5). If surgical 
resection is delayed for non-study drug related reasons, study drug may be continued beyond 
C6D18 (+14 days) only after discussion with the Medical Monitor. No participant should 
take study drug dispensed for the trial after surgical resection, and no study drug should be 
dispensed after surgical resection. 
Table 5 
Study Treatment 
Arm 
Study Drug 
Daily 
Dose 
Frequency 
Route of Administration 
A 
ARV-471 
200 mg 
Daily and continuously until day 
before surgical resection, but no 
later than C6D18 (+14 days) 
Oral 
B 
Anastrozole 
1 mg 
Daily and continuously until day 
before surgical resection, but no 
later than C6D18 (+14 days) 
Oral 
A cycle is defined as 28 days. If a treatment interruption continues beyond Day 28 of the 
current cycle, then the day treatment is restarted will be counted as Day 1 of the next cycle. 
Procedures required as per SoA on Day 1 of the given cycle will be performed when study 
treatment is resumed. 
6.1.1.1. Arm A 
Participants in Arm A will use 100 mg strength tablets of ARV-471. 


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• ARV-471 should be taken by mouth, QD. Participants must be instructed to take 
ARV-471 with food. Participants should be instructed to take ARV-471 at 
approximately the same time in the morning. Tablets must be swallowed whole and 
must not be crushed, chewed, or dissolved. 
• ARV-471 should be taken on the day of biopsy and the day the pre-surgical study 
labs are collected. 
• ARV-471 should be administered until the day before surgical resection (no later than 
C6D18 + 14 days). 
Participants taking ARV-471 will self-dose, except for scheduled clinic visits when 
ARV-471 should be withheld and taken while in the clinic (ie, not at home) under the 
supervision of study staff. 
6.1.1.2. Arm B 
Participants in Arm B will use 1 mg strength tablets of anastrozole. 
• Anastrozole should be taken by mouth once daily until the day before surgical 
resection.  
• Anastrozole should be taken on the day of biopsy and the day the pre-surgical study 
labs are collected. 
• Anastrozole should be administered until the day before surgical resection (no later 
than C6D18 + 14 days). 
• Additional information on anastrozole can be found in the locally approved product 
label. 
6.2. Preparation, Handling, Storage and Accountability 
• The IP should be stored in a secure area according to local regulations. It is the 
responsibility of the Investigator to ensure that IP is only dispensed to study 
participants. The IP must be dispensed only from official study sites by authorized 
personnel according to local regulations. 
• The IP storage manager should ensure that the study treatment is stored in accordance 
with the environmental conditions (temperature, light, and humidity) as determined 
by Arvinas. If concerns regarding the quality or appearance of the study treatment 
arise, the study treatment should not be dispensed, and Arvinas should be 
immediately contacted. 
• Study treatment not supplied by Arvinas will be stored in accordance with the 
package insert. 
• IP documentation (whether supplied by Arvinas or not) must be maintained that 
includes all processes required to ensure study treatment is accurately administered. 
This includes documentation of IP storage, dispensing processes, and administration. 
• Further guidance and information for final disposition of unused study treatment are 
provided in the study Pharmacy Manual. 


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6.2.1. Preparation and Dispensing 
Participants will be dispensed enough tablets of 100 mg of ARV-471 or 1 mg of anastrozole 
to last until the next scheduled clinic visit by the IRT. 
At each visit the participant should bring all bottles/cartons of IP along with their participant 
dosing diary for review by the site staff. 
The number of tablets in each bottle/carton should be recorded before dispensing and on 
return of bottles/cartons. 
6.2.2. Clinical Product Complaints 
A Clinical Product Complaint is defined as a problem or potential problem with the physical 
quality or characteristics of clinical drug supplies used in a clinical research study sponsored 
by Arvinas. Any product complaint associated with an IP supplied by the Sponsor are to be 
reported according to the instructions provided in the Pharmacy Manual. 
6.3. Assignment to Study Intervention  
This is an open-label randomized study. Randomization will be 2:1, and stratification will 
occur based on the following features of the participant’s breast cancer: 
• Size of primary breast tumor (T-stage): ≤2 cm, >2 to <5 cm, or ≥5 cm. 
• Ki-67 score (assessed locally): <20% or ≥20% 
Once screened, the participant will be registered in the IRT system to obtain the participant 
ID number. Study site users will receive log-in information and directions on how to access 
the IRT system. Specific instructions for using the IRT will be provided to the investigational 
site in a separate document. 
6.4. Study Intervention Compliance 
Treatment compliance will be monitored by drug accountability as well as the participant’s 
medical record and eCRF. 
Noncompliance is defined as taking less than 80% (providing no required dose interruptions 
occurred) or more than 120% of assigned study drug during any evaluation period. 
For participants receiving ARV-471 (Arm A):  
ARV-471 will be administered orally daily with food during each 28-day cycle. On days of 
scheduled clinic visits, study drug treatment should be withheld and taken while in the clinic 
(ie, not at home) under the supervision of study staff. Participants will self-dose as described 
above, with the exception of doses that will be administered at the clinic. 
At each visit where additional study drug will be dispensed, the previously dispensed study 
treatment will be retrieved by the study center and compliance assessed. Participants will be 
required to return all bottles and remaining tablets of ARV-471, as well as the completed 
participant diary for drug accountability and compliance. Participants are to complete the 
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required for C1 only. Participants exhibiting poor compliance as assessed by tablet counts 
should be counseled on the importance of good compliance to the study dosing regimen. 
For participants receiving anastrozole (Arm B):  
Anastrozole will be administered orally daily during each 28-day cycle. 
At each visit where additional study drug will be dispensed, the previously dispensed study 
treatment will be retrieved by the study center and compliance assessed. Participants will be 
required to return all bottles and remaining tablets of anastrozole, as well as the completed 
participant diary for drug accountability and compliance. Participants are to complete the 
study drug diary daily during study participation. Participants exhibiting poor compliance as 
assessed by tablet counts should be counseled on the importance of good compliance to the 
study dosing regimen. 
6.5. Dose Modification and Treatment Discontinuation 
The medical monitor or designee must be notified of any hold or dose modification of study 
drug. See Appendix 6 for suggested actions and follow-up on liver safety. 
During the week preceding surgical resection, if a participant experiences any AE that may 
be related to study drug and may impact surgical risk as per the treating physician, study drug 
must be discontinued, and surgery should be delayed until AEs have improved enough to 
allow a safe surgery per the treating investigator.  
Dosing for any individual participant may be interrupted (ie, treatment may be temporarily 
held) if the participant experiences an AE that, in the opinion of the Investigator or Sponsor’s 
medical representative, warrants a dose interruption for that participant’s wellbeing. Dosing 
must be interrupted for certain criteria as discussed in Sections 6.5 and 7. Prior to 
re-initiating study drug in a participant with a dosing interruption lasting >14 days, the 
Arvinas medical monitor or designee must be consulted. Periodic study visits to assess safety 
and laboratory studies should also continue as scheduled or more frequently if clinically 
indicated during such dosing interruptions. If a participant’s treatment is interrupted for more 
than 21 days, study treatment must be permanently discontinued. 
6.5.1. ARV-471 
• All Grade 4 AEs related to ARV-471 and considered to be clinically significant per 
treating investigator require permanent discontinuation of ARV-471. 
• For any Grade 3 thromboembolic event or cardiovascular event related to ARV-471, 
ARV-471 must be permanently discontinued.  
• For all ARV-471 related non-hematologic intolerable Grade 2 or Grade 3 AEs, 
participants should have their dose interrupted until the AE returns to ≤Grade 1 or 
baseline. Dose reduction should occur per Table 6. 
o Participants may resume treatment in the presence of Grade 2 fatigue. 


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• For all treatment-related Grade 3 hematologic toxicities, participants should have 
their dose interrupted until AEs return to Grade ≤2 or baseline. Dose reduction should 
occur per Table 6. 
• In the event of QTcF prolongation (regardless of causality), possible alternate 
reversible causes (eg, electrolytes, concomitant medications) should be evaluated. If 
reversible causes are identified, they should be corrected accordingly. If reversible 
causes are not identified, dose adjustments may be required as described below. 
o Grade 1: no adjustments or additional monitoring is required. 
o Grade 2: no adjustments are required. If the QTcF remains above 480 msec for 
more than 2 cycles or if Grade 2 QTcF prolongation recurs in the absence of other 
alternative causes or despite correction of alternative causes, dose adjustment 
and/or discontinuation should be considered in consultation with a cardiologist 
and the study medical monitor, taking into account the most current ARV-471 IB 
version, the emerging safety data from ARV-471 trials and the Investigator’s best 
medical judgment. Initiate more frequent ECG monitoring per PI judgement until 
QTcF ≤480 msec or ≤60 msec change from baseline.  
o Grade 3: withhold ARV-471 treatment until Grade ≤2. If an alternate reversible 
cause is identified and addressed, resume treatment at the same dose level. If a 
reversible cause is not identified, reduce ARV-471 by 1 dose level. Initiate more 
frequent ECG monitoring per PI judgement util QTcF ≤480 msec or ≤60 msec 
change from baseline.  
o Grade 4: permanently discontinue all study treatment. 


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Table 6 
Dose Reduction – Guidance for Adverse Events Related to ARV-471 (Except 
QTcF Prolongation) 
6.5.2. Anastrozole 
Please refer to the current anastrozole approved local product labeling for a summary of the 
expected safety profile in participants with HR+/HER2− breast cancer, including a full list of 
all Warnings and Precautions. 
• Dose modification of anastrozole is not allowed. 
• For Grade 4 AEs related to anastrozole considered to be clinically significant per 
treating investigator, anastrozole must be permanently discontinued. 
Management of AEs related to anastrozole should follow the most up to date local product 
labeling. 
6.6. Continued Access to Study Intervention After the End of the Study 
The Sponsor will not provide study drugs to participants after they leave the study. 
Participants should continue their care as normally expected for participants with breast 
cancer. 
6.7. Treatment of Overdose 
For this study, any dose of ARV-471 greater than 200 mg daily will be considered an 
overdose. 
Sponsor does not recommend specific treatment for an overdose. 
In the event of an overdose, the Investigator or qualified designee should: 
1. Contact the medical monitor within 24 hours. 
Intolerable Grade 2 AEs and  
Grade 3 AEs related to ARV-471a 
ARV-471 200 mg dose modification 
First dose reduction 
Reduce to 100 mg per dayb, c 
Second dose reduction 
Discontinue ARV-471 
Any Grade 4 AE related to ARV-471 or any Grade 3 
related to ARV-471 thromboembolic events or 
cardiovascular events 
Discontinue ARV-471 
Abbreviations: AE=adverse event 
a. 
Grade 3 AEs related to ARV-471 that do not require dose reduction: 
• 
Grade 3 fatigue lasting ≤7 days 
• 
Grade 3 lymphopenia lasting <72 hours  
• 
Grade 3 nausea/vomiting/diarrhea lasting ≤72 hours in the absence of maximal medical therapy 
b. Depending on the nature of the toxicity and the rapidity of recovery following dose interruption, resumption of the 
same dose may be considered after the first instance of the related Grade 3 AE or intolerable Grade 2 AE 
c. 
If the participant had a related Grade 2 intolerable AE, and the AE was rapidly reversible, and redosing 
is not expected to pose a significant risk to the participant, one dose re-escalation of ARV-471 may be 
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2. Closely monitor the participant for any AEs/SAEs and laboratory abnormalities for at 
least 5 half-lives or 28 calendar days after the overdose of ARV-471 (whichever is 
longer).  
3. Document the quantity of the excess dose as well as the duration of the overdose in 
the CRF. 
4. Overdose is reportable to the sponsor only when associated with an SAE. 
5. Obtain a blood sample for PK analysis if requested by the medical monitor 
(determined on a case-by-case basis). 
Decisions regarding dose interruptions or modifications will be made by the investigator in 
consultation with the medical monitor based on the clinical evaluation of the participant. 
There is no known antidote for anastrozole overdose. General supportive measures should be 
taken (refer to anastrozole local product label). 
6.8. Prior and Concomitant Therapy 
Any vaccine (see COVID information in Appendix 9) or medication (Appendix 8), including 
over the counter or prescription medicines, vitamins, physiologic replacement doses of 
systemically administered corticosteroids, and/or herbal supplements that the participant is 
receiving at the time of enrollment (within 28 days before the time of enrollment) or receives 
during the study must be recorded in the eCRF along with: 
• Reason for use. 
• Dates of administration including start and end dates. 
• Dosage information including dose and frequency. 
The Medical Monitor should be contacted if there are any questions regarding concomitant or 
prior therapy. 
Herbal supplements are not recommended. Other concomitant medications may be 
considered on a case-by-case basis by the Investigator in consultation with the Medical 
Monitor, as necessary. 
6.8.1. Prohibited Therapy 
Known prior medications that exclude a participant from participating in the study are 
described in the exclusion criteria (Section 5.2). 
6.8.1.1. ARV-471 
Participants enrolled in this clinical study receiving ARV-471 will not be allowed to receive 
the following medications, food or herbal supplements (Appendix 8). Unless otherwise 
specified, these substances should be discontinued at least 14 days prior to starting ARV-471. 
• Strong inducers/inhibitors of CYP3A4 
• Sensitive P-gp substrates or those with narrow therapeutic indices 


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• Any medications that are known to prolong the QT interval, and/or are associated 
with a risk of Torsades de Pointes, within 7 days prior to first dose of ARV-471 and 
during the study, unless they are being used with caution to treat a drug-related AE 
when no alternative is available. 
Co-administration of gastric acid-reducing agents may reduce ARV-471 absorption. The 
concomitant use of PPIs with ARV-471 is not recommended. If PPI treatment is required, 
ARV-471 drug intake with a moderate-fat meal (400-800 calories, approximately 35% fat) is 
recommended. 
H2 blockers (eg, cimetidine, famotidine) or local antacids (eg, aluminum hydroxide, calcium 
carbonate, bismuth subsalicylate) may be used. Administer ARV-471 ≥2 hours before or 
after antacids. Administer ARV-471 ≥2 hours before or 10 to 12 hours after H2 blockers. 
For additional information regarding concomitant use of ARV-471 with PPIs or H2 blockers, 
refer to the most current ARV-471 IB version. 
6.8.1.2. Anastrozole 
Participants enrolled in this clinical study receiving anastrozole will not be allowed to receive 
medications that are excluded in the anastrozole USPI or local label. Please refer to the USPI 
or local label for additional information. 
6.8.1.3. Other Prohibited and/or Limited use of Anti-tumor/Anti-Cancer or 
Experimental Drugs, or Procedures 
• Other therapies with known anti-cancer effects (including radiation therapy) are 
prohibited on study prior to surgical resection.  
6.8.2. Other Restrictions and Precautions 
Participants are not allowed to consume grapefruit juice while receiving ARV-471. Study 
drugs should be administered as per Section 6.1. Other lifestyle restrictions are described in 
Section 5.3.  
Participation in any interventional or non-interventional investigational studies should be 
discussed with the Medical Monitor. 
6.8.3. Supportive Care 
Palliative and supportive care for disease related symptoms may be administered at the 
investigator’s discretion and according to the specific supportive care product Prescribing 
Information or the current ASCO guidelines.  
6.9. Surgical Resection 
Participants should undergo definitive surgical resection approximately 5.5 months after 
starting study treatment (C6D18 ± 14 days). 


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Surgery should be performed in accordance with standard local guidelines as agreed upon by 
the surgeon and participant. Pathological staging (ypT, ypN) must be performed on the 
resected sample and must be available for data entry and monitoring. 
During the week preceding surgical resection, if a participant experiences any AE that may 
be related to study drug and may impact surgical risk as per the treating physician, study drug 
should be discontinued (if applicable) and surgery should be delayed until AEs have 
improved enough to allow a safe surgery per the treating investigator. 
After surgery, participants will receive SOC radiation and systemic therapy (chemotherapy, 
endocrine therapy, etc.) in accordance with local practice guidelines per the treating 
physician’s discretion. 
7. DISCONTINUATION OF STUDY INTERVENTION AND PARTICIPANT 
DISCONTINUATION/WITHDRAWAL 
7.1. Criteria for Stopping the Study 
The Sponsor may terminate this study prematurely, either in its entirety or at any study site, 
for reasonable cause provided that written notice is submitted in advance of the intended 
termination. The Investigator may also terminate the study at his/her site for reasonable 
cause, after providing written notice to the Sponsor in advance of the intended termination. 
Advance notice is not required by either party if the study is stopped due to safety concerns. 
If the Sponsor terminates the study for safety reasons, the Sponsor will immediately notify 
the Investigator by telephone and subsequently provide written instructions for study 
termination. 
The Sponsor (and/or regulatory agency) reserves the right to discontinue the study for 
medical and/or administrative reasons at any time. 
Conditions that may cause termination of the study in its entirety or an individual study site 
may include but are not limited to: 
• The discovery of an unexpected, serious, or unacceptable risk to any participant 
enrolled in the study. 
• The Sponsor’s decision to suspend or discontinue further testing or evaluation of the 
drug under study. 
• The failure of the Investigator to comply with the approved protocol, appropriate 
guidelines, and applicable regulations. 
• Submission of intentionally or knowingly false information from the Investigator to 
the Sponsor. 
7.2. Discontinuation of Study Intervention 
It may be necessary for a participant to permanently discontinue study intervention. Reasons 
for permanent discontinuation of study intervention may include the following: 
• Significant global deterioration of health status requiring discontinuation; 


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• Objective disease progression, or occurrence of a second malignancy that requires 
systemic therapy or radiotherapy for treatment. 
• Unacceptable toxicity and/or AE warranting discontinuation of ARV-471 or 
anastrozole as described in Section 6.5. 
• Significant protocol violation; 
• Loss of ability to freely provide consent through imprisonment or involuntarily 
incarceration for treatment of either a psychiatric or physical (eg, infectious disease) 
illness. 
• Lost to follow-up; 
• Participant refused further treatment; 
• Study terminated by sponsor; 
• Death; 
Note that discontinuation of study intervention does not represent withdrawal from the study. 
If study intervention is permanently discontinued, the participant will remain in the study to 
be evaluated for protocol specified follow-up procedures as outlined in the SoA 
(Section 1.3). The only exception to this requirement is when a participant withdraws consent 
for all study procedures including post-treatment study follow-up or loses the ability to 
consent freely (ie, is imprisoned or involuntarily incarcerated for the treatment of either a 
psychiatric or physical illness). 
In the event of discontinuation of study intervention, it must be documented on the 
appropriate CRF/in the medical records whether the participant is discontinuing further 
receipt of study intervention or also from study procedures, posttreatment study follow-up, 
and/or future collection of additional information. 
7.3. Participant Discontinuation/Withdrawal From the Study  
A participant may withdraw from the study at any time at their own request. Reasons for 
discontinuation from the study may include: 
• Refused further study procedures; 
• Lost to follow-up; 
• Death; 
• Study terminated by sponsor. 
The participant will be permanently discontinued from the study intervention and the study at 
that time. 
If the participant withdraws from the study and also withdraws consent (Section 7.3.1) for 
disclosure of future information, no further evaluations should be performed and no 
additional data should be collected. The sponsor may retain and continue to use any data 
collected before such withdrawal of consent. 


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7.3.1. Withdrawal of Consent  
Participants who request to discontinue receipt of study intervention will remain in the study 
and must continue to be followed for protocol-specified follow-up procedures. The only 
exception to this is when a participant specifically withdraws consent for any further contact 
with him or her or persons previously authorized by the participant to provide this 
information. Participants should notify the investigator in writing of the decision to withdraw 
consent from future follow-up, whenever possible. The withdrawal of consent should be 
explained in detail in the medical records by the investigator, as to whether the withdrawal is 
only from further receipt of study intervention or also from study procedures and/or 
posttreatment study follow-up, and entered on the appropriate CRF page. If vital status 
(whether the participant is alive or dead) is being measured, publicly available information 
should be used to determine vital status only as appropriately directed in accordance with 
local law. 
7.4. Lost to Follow-Up  
A participant will be considered lost to follow-up if he or she repeatedly fails to return for 
scheduled visits and is unable to be contacted by the study site. All reasonable efforts must 
be made to locate participants to determine and report their ongoing status. This includes 
follow-up with persons authorized by the participant. Lost to follow-up is defined by the 
inability to reach the participant after a minimum of three documented phone calls, faxes, or 
emails as well as lack of response by participant to one registered mail letter. All attempts 
should be documented in the participant’s medical records 
The following actions must be taken if a participant fails to return to clinic for a required 
study visit: 
• The site must attempt to contact the participant and reschedule the missed visit as 
soon as possible. Counsel the participant on the importance of maintaining the 
assigned visit schedule and ascertain whether the participant wishes to and/or should 
continue in the study. 
• Before a participant is deemed lost to follow-up, the investigator or designee must 
make every effort to regain contact with the participant (where possible, 3 telephone 
calls and, if necessary, a certified letter to the participant’s last known mailing 
address or local equivalent methods). These contact attempts should be documented 
in the participant’s medical record. 
• Should the participant continue to be unreachable, he/she will be considered to have 
withdrawn from the study.  
• The site staff and representative will consult publicly available sources, such as 
public health registries and databases, in order to obtain updated contact information. 
• If investigator’s use of third-party representative to assist in the follow-up portion of 
the study has been included in the participant’s informed consent, then the 
investigator may use a Sponsor-retained third-party representative to assist site staff 
with obtaining participant’s contact information or other public vital status data 
necessary to complete the follow-up portion of the study.  


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• If it is determined that the participant has died, the site will use permissible local 
methods to obtain date and cause of death. 
• If after all attempts, the participant remains lost to follow-up, then the last known 
alive date as determined by the investigator should be reported and documented in the 
participant’s medical records. 
8. STUDY ASSESSMENTS AND PROCEDURES 
The investigator (or an appropriate delegate at the investigator site) must obtain a signed and 
dated ICD before performing any study-specific procedures.  
Study procedures and their timing are summarized in the SoA (Section 1.3). Protocol waivers 
or exemptions (including but not limited to eligibility) are not allowed. 
Safety issues should be discussed with the sponsor immediately upon occurrence or 
awareness to determine whether the participant should continue or discontinue study 
intervention. 
Adherence to the study design requirements, including those specified in the SoA 
(Section 1.3), is essential and required for study conduct. 
All screening evaluations must be completed and reviewed to confirm that potential 
participants meet all eligibility criteria. The investigator will maintain a screening log to 
record details of all participants screened and to confirm eligibility or record reasons for 
screening failure, as applicable. 
Procedures conducted as part of the participant’s routine clinical management (eg, blood 
count) and obtained before signing of the ICD may be utilized for screening or baseline 
purposes provided the procedures met the protocol-specified criteria and were performed 
within the time frame defined in the SoA (Section 1.3). 
Every effort should be made to ensure that protocol-required tests and procedures are 
completed as described. However, it is anticipated that from time to time there may be 
circumstances outside the control of the investigator that may make it unfeasible to perform 
the test. In these cases, the investigator must take all steps necessary to ensure the safety and 
well-being of the participant. When a protocol-required test cannot be performed, the 
investigator will document the reason for the missed test and any corrective and preventive 
actions that he or she has taken to ensure that required processes are adhered to as soon as 
possible. The study team must be informed of these incidents in a timely manner. 
For samples being collected and shipped, detailed collection, processing, storage, and 
shipment instructions and contact information will be provided to the investigator site prior 
to initiation of the study. 
Additional measures, including non-study required laboratory tests, should be performed as 
clinically indicated or to comply with local regulations. Laboratory toxicities (eg, suspected 
drug-induced liver enzyme evaluations) will be monitored during the follow-up phase via 


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on-site/local labs until all study drug related toxicities resolve, return to baseline, or are 
deemed irreversible. 
Some of the assessments referred to in this section may not be captured as data in the eCRF. 
They are intended to be used as safety monitoring by the treating physician. Additional 
testing or assessments may be performed as clinically necessary or where required by 
institutional or local regulations. 
8.1. Efficacy Assessments 
8.1.1. Disease Response Assessment 
8.1.1.1. Imaging and Clinical Assessment 
To meet the study’s exploratory objectives related to assessment of anti-tumor response, 
preliminary antitumor activity of ARV-471 and anastrozole, respectively, will be evaluated 
through tumor assessment imaging, tumor measurement on physical exam, and assessment of 
pathologic stage/residual disease. Study evaluations will take place in accordance with the 
SoA (Section 1.3). 
8.1.1.2. Radiographic Imaging Assessment 
Radiographic imaging (eg, breast ultrasound, breast MRI with contrast, and/or mammogram) 
is required during Screening, C4D1, and prior to surgical resection. Contrast enhanced breast 
MRI is the preferred imaging modality. The same imaging method used at baseline must also 
be used at all post baseline imaging visits (ie, C4D1, within 7 days prior to surgical resection 
and any unscheduled imaging visits performed to assess the primary breast tumor). 
Breast imaging conducted as part of the participant’s routine clinical management (eg, 
ultrasound, MRI, mammogram) and obtained before signing of the ICD may be utilized for 
Screening or baseline purposes provided the procedures met the protocol-specified criteria 
and were performed within the time frame defined in the SoA (Section 1.3). Full staging 
scans during or prior to screening may be performed, if necessary, at the discretion of the 
investigator as per SOC.  
Tumor imaging response assessment will be performed according to modified RECIST 1.1 
criteria. The primary breast tumor must be measurable with a size of at least 1.5 cm (15 mm) 
in the longest diameter. Additional lesions identified on breast imaging may be followed for 
response as outlined in Appendix 11.  
8.1.1.3. Physical Exam: Caliper-based Measurements 
Caliper based measurements of the primary breast tumor must be performed in accordance 
with the SoA (Section 1.3). 
8.1.1.4. Local Pathological Assessment of Tissue from Surgical Resection 
Local pathological assessment of the tissue from surgical resection (performed after 
approximately 5.5 months of treatment), at minimum, should include pathologic stage (ypT 
and ypN stage) as described in the Laboratory Manual. Pathologic complete response will be 
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specimen and all sampled regional lymph nodes following completion of neoadjuvant 
systemic therapy (ie, ypT0/T is ypN0 in the current AJCC staging system).  
8.2. Safety Assessments 
Safety will be evaluated through AE monitoring, clinical evaluations (ie, vital signs, physical 
exams, ECGs), and laboratory tests (ie, hematology, serum chemistries).  
Any clinically significant changes, in the opinion of the Investigator, noted during 
abbreviated or final physical examinations, ECG evaluations, and any other safety 
assessments, whether or not these procedures are required by the protocol, should also be 
recorded in the appropriate AE page of the eCRF, including information regarding NCI 
CTCAE v5.0 grade, relationship to study drug, any action taken, date of onset and outcome 
Appendix 3. 
Planned time points for all safety assessments are provided in SoA (Table 2). Unscheduled 
clinical laboratory measurements may be obtained at any time during the study to assess any 
perceived safety issues. 
8.2.1. Physical Examinations 
A complete physical examination will include, at a minimum, assessments of the breasts, 
neck/axillary lymph nodes, cardiovascular, respiratory, GI, and musculoskeletal systems. An 
abbreviated physical examination will be symptom directed.  
The physical examination should be performed by the same person each time when possible. 
Investigators should pay special attention to clinical signs related to previous serious 
illnesses. 
Physical examinations may be conducted by a physician, trained physician's assistant, or 
nurse practitioner as acceptable according to local regulation.  
Physical examination findings collected during the study will be considered source data and 
will not be required to be reported, unless otherwise noted. Any untoward physical 
examination findings that are identified during the active collection period and meet the 
definition of an AE or SAE (Appendix 3) must be reported according to the processes in 
Sections 8.3.1 to 8.3.4. 
8.2.2. Vital Signs 
Temperature assessments may be oral or tympanic. BP and pulse measurements will be 
assessed while the participant is in a sitting position or semi recumbent position 
(recommended). The same position should be used throughout the study. Manual techniques 
will be used only if an automated device is not available. 
BP and pulse measurements should be preceded by approximately five minutes of rest for the 
participant in a quiet setting without distractions (eg, television, cell phones).  


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8.2.3. Electrocardiograms 
Screening ECGs will be single 12-lead ECGs and are not required to be obtained on vendor 
machines. Starting at C1D1 (pre-dose, baseline), triplicate 12-lead ECGs will be obtained 
using vendor ECG machines that automatically calculates the heart rate and measures pulse 
rate, QRS, QT, and QTcF intervals. If screening ECG is obtained on a vendor machine 
within 96 hours of C1D1 in triplicate, there is no need to repeat the pre-dose ECG testing on 
C1D1. 
All scheduled ECGs should be performed after the participant has rested quietly for at least 
5 minutes in a supine position. Triplicate ECGs are defined as three consecutive ECGs 
performed approximately 2 minutes apart but within 10 minutes for all 3 measurements as 
per Table 2 to determine the QTc interval. 
All triplicate ECG tracings will be sent electronically to a central ECG laboratory for manual 
interval measurements. The final ECG reports from the central ECG laboratory should be 
maintained in the participant's source documentation. 
All ECG’s must be reviewed by qualified personnel at the site, including verifying that the 
machine reading is accurate, and that the Fridericia correction formula is applied. 
If vendor ECG machine readings return an abnormal ECG finding considered clinically 
significant by the investigator, the investigator may use their site machine to repeat the 
assessment. If both the site and vendor machines return an abnormal ECG finding, then the 
investigator should follow the guidance provided in section 6.5 of the protocol, if applicable. 
The investigator should consult a cardiologist per their institutional guidelines. The sites 
should manually upload the ECGs from the site machine into the Clario ERT portal.  
Treatment interruption and discontinuation criteria for QTcF prolongation are listed in 
Section 6.5. 
ECG values of potential clinical concern are listed in Appendix 7. 
8.2.4. Clinical Safety Laboratory Assessments 
See Appendix 2 for the list of clinical safety laboratory tests to be performed and the SoA 
(Section 1.3) for the timing and frequency. All protocol-required laboratory assessments, as 
defined in Appendix 2, must be conducted in accordance with the Laboratory Manual and the 
SoA (Section 1.3). The SoA also includes information on allowable windows for testing and 
windows for screening tests to be used for C1D1. Unscheduled clinical laboratory 
measurements may be obtained at any time during the study to assess any perceived safety 
issues.  
The investigator must review the laboratory report, document this review, and record any 
clinically relevant changes occurring during the study in the AE section of the CRF. 
Clinically significant abnormal laboratory findings are those which are not associated with 
the underlying disease, unless judged by the investigator to be more severe than expected for 
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All laboratory tests with values considered clinically significantly abnormal during 
participation in the study or within 28 days after the last dose of study intervention should be 
repeated until the values return to normal or baseline or are no longer considered clinically 
significant by the investigator or medical monitor. 
If such values do not return to normal/baseline within a period of time judged reasonable by 
the investigator, the etiology should be identified and the sponsor notified. 
See Appendix 6 for suggested actions and follow-up assessments in the event of a potential 
DILI. 
No need to repeat clinical laboratory assessments on C1D1 if the baseline assessment was 
performed within 96 hours prior to that date. 
For participant convenience, the blood tests performed during any non-clinic visit (except PK 
or biomarker collections) day may be performed at the study center or locally (ie, licensed 
laboratory) and the lab results sent to the Principal Investigator. 
If laboratory values from non-protocol specified laboratory assessments performed at the 
institution’s local laboratory require a change in participant management or are considered 
clinically significant by the Investigator (eg, SAE, AE, or dose modification), then the results 
must be recorded in the eCRF. 
8.3. Adverse Events, Serious Adverse Events, and Other Safety Reporting 
The definitions of an AE and an SAE can be found in Appendix 3. 
AEs may arise from symptoms or other complaints reported to the investigator by the 
participant (or, when appropriate, by a caregiver, surrogate, or the participant's legally 
authorized representative), or they may arise from clinical findings of the Investigator or 
other healthcare providers (clinical signs, test results, etc.).  
The investigator and any qualified designees are responsible for detecting, documenting, and 
recording events that meet the definition of an AE or SAE and remain responsible to pursue 
and obtain adequate information both to determine the outcome and to assess whether the 
event meets the criteria for classification as an SAE or caused the participant to discontinue 
the study intervention (Section 7.2).  
During the active collection period as described in Section 8.3.1, each participant will be 
questioned about the occurrence of AEs in a nonleading manner.  
In addition, the investigator may be requested by Pfizer Safety to obtain specific follow-up 
information in an expedited fashion. 
8.3.1. Time Period and Frequency for Collecting AE and SAE Information 
The time period for actively eliciting and collecting AEs and SAEs (“active collection 
period”) for each participant begins from the time the participant provides informed consent, 
which is obtained before the participant’s participation in the study (ie, before undergoing 


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any study related procedure and/or receiving study intervention), through and including a 
minimum of 30 calendar days after the last administration of the study intervention (ie, study 
drug treatment or surgical resection, whichever occurs last). 
Follow-up by the investigator continues throughout and after the active collection period and 
until the AE or SAE or its sequelae resolve or stabilize at a level acceptable to the 
investigator. 
When a clinically important AE remains ongoing at the end of the active collection period, 
follow-up by the investigator continues until the AE or SAE or its sequelae resolve or 
stabilize at a level acceptable to the investigator and Pfizer concurs with that assessment. 
For participants who are screen failures, the active collection period ends when screen failure 
status is determined. 
If the participant withdraws from the study and also withdraws consent for the collection of 
future information, the active collection period ends when consent is withdrawn. 
If a participant permanently discontinues or temporarily discontinues study intervention 
because of an AE or SAE, the AE or SAE must be recorded on the CRF and the SAE 
reported using the SAE Report Form. 
Investigators are not obligated to actively seek information on AEs or SAEs after the 
participant has concluded study participation. However, if the investigator learns of any SAE, 
including a death, at any time after a participant has completed the study, and he/she 
considers the event to be reasonably related to the study intervention, the investigator must 
promptly report the SAE to Pfizer using the SAE Report Form. 
8.3.1.1. Reporting SAEs to Pfizer Safety 
All SAEs occurring in a participant during the active collection period as described in 
Sections 8.3.1 are reported to Pfizer Safety on the SAE Report Form immediately upon 
awareness and under no circumstance should this exceed 24 hours, as indicated in Appendix 
3. The investigator will submit any updated SAE data to the sponsor within 24 hours of it 
being available. 
If a participant begins a new anticancer therapy, SAEs occurring during the above-indicated 
active collection period must still be reported to Pfizer Safety irrespective of any intervening 
treatment. Note that a switch to a commercially available version of the study intervention is 
considered as a new anticancer therapy for purposes of SAE reporting. 
8.3.1.2. Recording Nonserious AEs and SAEs on the CRF 
All AEs and SAEs occurring in a participant during the active collection period which begins 
after obtaining informed consent, as described in Section 8.3.1, will be recorded on the AE 
section of the CRF. The recording of non-serious AEs and SAEs will continue until 30 days 
after last administration of study intervention. Participants who undergo surgical resection 
>6 weeks after the last dose of study drug will have AEs collected for 42 days after the last 
dose of study drug. 


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The investigator is to record on the CRF all directly observed and all spontaneously reported 
AEs and SAEs reported by the participant. 
Reporting of AEs and SAEs for participants who fail screening are subject to the CRF 
requirements as described in Section 5.4. 
If a participant begins a new anticancer therapy, the recording period for nonserious AEs 
ends at the time the new treatment is started; however, SAEs must continue to be recorded on 
the SAE CRF during the above-indicated active collection period. Note that a switch to a 
commercially available version of the study intervention is considered as a new anticancer 
therapy for the purposes of SAE reporting. 
8.3.2. Method of Detecting AEs and SAEs 
The method of recording, evaluating, and assessing causality of AEs and SAEs and the 
procedures for completing and transmitting SAE reports are provided in Appendix 3. 
Care will be taken not to introduce bias when detecting AEs and/or SAEs. Open and 
nonleading verbal questioning of the participant is the preferred method to inquire about 
AE occurrences. 
8.3.3. Follow-Up of AEs and SAEs 
After the initial AE or SAE report, the investigator is required to proactively follow each 
participant at subsequent visits/contacts. For each event, the investigator must pursue and 
obtain adequate information until resolution, stabilization, the event is otherwise explained, 
or the participant is lost to follow-up (Section 7.4). 
In general, follow-up information will include a description of the event in sufficient detail to 
allow for a complete medical assessment of the case and independent determination of 
possible causality. Any information relevant to the event, such as concomitant medications 
and illnesses, must be provided. In the case of a participant death, a summary of available 
autopsy findings must be submitted as soon as possible to Pfizer Safety.  
Further information on follow-up procedures is given in Appendix 3. 
8.3.4. Regulatory Reporting Requirements for SAEs 
Prompt notification by the investigator to the sponsor of an SAE is essential so that legal 
obligations and ethical responsibilities toward the safety of participants and the safety of a 
study intervention under clinical investigation are met. 
The sponsor has a legal responsibility to notify both the local regulatory authority and other 
regulatory agencies about the safety of a study intervention under clinical investigation. The 
sponsor will comply with country-specific regulatory requirements relating to safety 
reporting to the regulatory authority, IRBs/ECs, and investigators. 
Investigator safety reports must be prepared for SUSARs according to local regulatory 
requirements and sponsor policy and forwarded to investigators, as necessary. 


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An investigator who receives SUSARs or other specific safety information (eg, summary or 
listing of SAEs) from the sponsor will review and then file it along with the SRSD(s) and 
will notify the IRB/EC, if appropriate according to local requirements. 
8.3.5. Environmental Exposure, Exposure During Pregnancy or Breastfeeding, and 
Occupational Exposure 
Environmental exposure occurs when a person not enrolled in the study as a participant 
receives unplanned direct contact with or exposure to the study intervention. Such exposure 
may or may not lead to the occurrence of an AE or SAE. Persons at risk for environmental 
exposure include healthcare providers, family members, and others who may be exposed. An 
environmental exposure may include EDP, EDB, and occupational exposure. 
Any such exposure to the study intervention under study are reportable to the sponsor within 
24 hours of investigator awareness. 
8.3.5.1. Exposure During Pregnancy 
An EDP occurs if:  
• A female is found to be pregnant while being exposed or having been exposed to 
study intervention due to environmental exposure. Below are examples of 
environmental EDP:  
o A female family member or healthcare provider reports that she is pregnant after 
having been exposed to the study intervention by ingestion or skin contact.  
o A male family member or healthcare provider who has been exposed to the 
study intervention by ingestion, or skin contact then exposes his female 
partner prior to or around the time of conception. 
The investigator must report EDP to Pfizer Safety within 24 hours of the investigator’s 
awareness, irrespective of whether an SAE has occurred. The initial information submitted 
should include the anticipated date of delivery (see below for information related to 
termination of pregnancy).  
• If EDP occurs in a participant’s partner, the investigator must report this information 
to Pfizer Safety on the SAE Report Form and an EDP Supplemental Form, regardless 
of whether an SAE has occurred. Details of the pregnancy will be collected after the 
start of study intervention and until 28 days after the last ARV-471 or anastrozole 
dose. 
• If EDP occurs in the setting of environmental exposure, the investigator must report 
information to Pfizer Safety using the SAE Report Form and EDP Supplemental 
Form. Since the exposure information does not pertain to the participant enrolled in 
the study, the information is not recorded on a CRF; however, a copy of the 
completed SAE Report Form is maintained in the investigator site file. 
Follow-up is conducted to obtain general information on the pregnancy and its outcome for 
all EDP reports with an unknown outcome. The investigator will follow the pregnancy until 
completion (or until pregnancy termination) and notify Pfizer Safety of the outcome as a 


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follow-up to the initial EDP Supplemental Form. In the case of a live birth, the structural 
integrity of the neonate can be assessed at the time of birth. In the event of a termination, the 
reason(s) for termination should be specified and, if clinically possible, the structural 
integrity of the terminated fetus should be assessed by gross visual inspection (unless 
preprocedure test findings are conclusive for a congenital anomaly and the findings are 
reported). 
Abnormal pregnancy outcomes are considered SAEs. If the outcome of the pregnancy meets 
the criteria for an SAE (ie, ectopic pregnancy, spontaneous abortion, intrauterine fetal 
demise, neonatal death, or congenital anomaly in a live-born baby, a terminated fetus, an 
intrauterine fetal demise, or a neonatal death), the investigator should follow the procedures 
for reporting SAEs. Additional information about pregnancy outcomes that are reported to 
Pfizer Safety as SAEs follows:  
• Spontaneous abortion including miscarriage and missed abortion; 
• Neonatal deaths that occur within 1 month of birth should be reported, without regard 
to causality, as SAEs. In addition, infant deaths after 1 month should be reported as 
SAEs when the investigator assesses the infant death as related or possibly related to 
exposure to the study intervention.  
Additional information regarding the EDP may be requested by the sponsor. Further 
follow-up of birth outcomes will be handled on a case-by-case basis (eg, follow-up on 
preterm infants to identify developmental delays). In the case of paternal exposure, the 
investigator will provide the participant with the Pregnant Partner Release of Information 
Form to deliver to his partner. The investigator must document in the source documents that 
the participant was given the Pregnant Partner Release of Information Form to provide to his 
partner. 
8.3.5.2. Exposure During Breastfeeding 
An EDB occurs if:  
• A female is found to be breastfeeding while being exposed or having been exposed to 
study intervention (ie, environmental exposure). An example of environmental EDB 
is a female family member or healthcare provider who reports that she is 
breastfeeding after having been exposed to the study intervention by ingestion or skin 
contact.  
The investigator must report EDB to Pfizer Safety within 24 hours of the investigator’s 
awareness, irrespective of whether an SAE has occurred. The information must be reported 
using the SAE Report Form. When EDB occurs in the setting of environmental exposure, the 
exposure information does not pertain to the participant enrolled in the study, so the 
information is not recorded on a CRF. However, a copy of the completed SAE Report Form 
is maintained in the investigator site file. 
An EDB report is not created when a Pfizer drug specifically approved for use in 
breastfeeding women (eg, vitamins) is administered in accord with authorized use. However, 


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if the infant experiences an SAE associated with such a drug, the SAE is reported together 
with the EDB. 
8.3.5.3. Occupational Exposure 
The investigator must report any instance of occupational exposure to Pfizer Safety within 
24 hours of the investigator’s awareness using the SAE Report Form regardless of whether 
there is an associated SAE. Since the information about the occupational exposure does not 
pertain to a participant enrolled in the study, the information is not recorded on a CRF; 
however, a copy of the completed SAE Report Form must be maintained in the investigator 
site file. 
8.3.6. Lack of Efficacy 
The investigator must report signs, symptoms, and/or clinical sequelae resulting from lack of 
efficacy. Lack of efficacy or failure of expected pharmacological action is reportable to the 
sponsor only if associated with an SAE.  
8.3.7. Medication Errors 
Medication errors may result from the administration or consumption of the study 
intervention by the wrong participant, or at the wrong time, or at the wrong dosage strength.  
Medication errors are recorded and reported as follows: 
Recorded on the 
Medication Error page 
of the CRF 
Recorded on the  
Adverse Event page  
of the CRF 
Reported on the CT SAE 
Report Form to Pfizer Safety 
Within 24 Hours of 
Awareness 
All (regardless of 
whether associated with 
an AE) 
Any AE or SAE associated 
with the medication error 
Only if associated with an SAE 
Medication errors include: 
• Medication errors involving participant exposure to the study intervention; 
• Potential medication errors or uses outside of what is foreseen in the protocol that do 
or do not involve the study participant. 
Such medication errors occurring to a study participant are to be captured on the medication 
error page of the CRF, which is a specific version of the AE page. 
In the event of a medication dosing error, the sponsor should be notified within 24 hours. 
Whether or not the medication error is accompanied by an AE, as determined by the 
investigator, the medication error is recorded on the medication error page of the CRF and, if 
applicable, any associated AE(s), serious and nonserious, are recorded on the AE page of the 
CRF.  


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Medication errors should be reported to Pfizer Safety within 24 hours on a SAE Report Form 
only when associated with an SAE. 
8.4. Pharmacokinetics 
For participants receiving ARV-471 only (Arm A), blood sampling for PK analysis will be 
conducted as specified in Table 3. 
8.4.1. Collection of Samples 
For participants receiving ARV-471, venous blood samples will be collected for PK. At visits 
during which blood samples for the determination of multiple aspects of study treatment will 
be taken, one sample of sufficient volume can be used. Additional samples may be collected 
at additional time points during the study if agreed upon between the Investigator and the 
Sponsor (eg, insufficient sample volume to complete testing or to help assess or follow up on 
any suspected drug-related AE). 
The actual date and time (24-hour clock time) of each PK sample will be collected and 
recorded in the eCRF. The actual dose amount, date, and time of the previous ARV-471 dose 
and at least one subsequent dose in each PK sample collection day will be recorded. PK 
samples will be collected, processed, labeled, stored, and shipped as detailed in the study 
Laboratory Manual. 
8.4.1.1. Determination of Drug Concentration 
PK samples for the determination of ARV-471 and ARV-473 in plasma will be analyzed 
using a validated bioanalytical method measuring both ARV-471 and ARV-473 using a 
chiral assay. Full details of the bioanalytical methods will be described in separate 
Bioanalytical Reports. All PK samples within the known stability window at the time of 
receipt by the bioanalytical laboratory will be analyzed. Plasma samples may be subjected to 
further analysis by the Sponsor or designee for the purpose of the development of additional 
bioanalytical assays and/or to investigate the presence of ARV-471 and/or its metabolites. 
Samples collected for analyses of concentrations of ARV-471 and ARV-473 may also be 
used to evaluate safety or efficacy aspects related to concerns arising during or after the 
study. 
8.4.1.2. Determination of Pharmacokinetic of Individual Participants 
Plasma concentrations of ARV-471 and ARV-473 from sparse PK sampling will be analyzed 
using population PK approach to determine exposure and clearance parameter values for 
individuals. The effects of concomitant medications, participant demographics (eg, race, age, 
body size), and intrinsic factors such as renal or hepatic functions on ARV-471 and ARV-
473 will be explored. A separate population PK report may be issued following the 
completion of the study. 
8.5. Genetics 
8.5.1. Specified Genetics 
Genetics (specified analyses) are not evaluated in this study. 


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8.6. Biomarkers 
Local assessment of Ki-67 will be used for randomization.  
On study Ki-67 and ER testing will be conducted in certified Clinical Laboratory 
Improvement Amendments central testing laboratories. Ki-67 expression will be measured 
by IHC. ER expression will be measured by quantitative immunofluorescence. These 
analyses will be done in a blinded manner at the central laboratories. 
Analysis of additional PD and other biomarkers thought to play a role in breast cancer or 
drug response may also be performed including, but not limited to, PgR expression, 
 
 
 
 
Samples may be stored for a maximum of 10 years (or according to local regulations) 
following the last participant’s last visit for the study at a facility selected by the Sponsor to 
enable further analysis of biomarker responses to the study drugs. 
8.6.1. Mandatory Tumor Biopsies 
Tumor samples for PD endpoints and other biomarker research that should be collected from 
participants are: 
• Screening: 3 to 5 core biopsies from the primary breast tumor 
• On-treatment biopsy on C1D15 (+5 days): 3 to 5 core biopsies from the primary 
breast tumor 
• Tumor samples from surgical resection (after approximately 5.5 months of 
treatment): equivalent of 3 to 5 core biopsies, at minimum 
Details on biopsy collection and processing are provided in the Laboratory Manual. 
9. STATISTICAL CONSIDERATIONS 
Detailed methodology for summary and statistical analyses of the data collected in this study 
is outlined here and further detailed in the SAP, which will be maintained by the sponsor. 
The SAP may modify what is outlined in the protocol where appropriate; however, any major 
modifications of the primary endpoint definitions or their analyses will also be reflected in a 
protocol amendment. 
9.1. Statistical Hypotheses 
9.1.1. Multiplicity Adjustment 
This is a Phase 2 POC study designed to generate data informing future studies about 
ARV-471. There are no plans for formal comparisons or hypotheses testing. There is no need 
for Type I error control. 


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9.1.2. Estimands 
9.1.2.1. Primary Estimands 
The primary estimand of this study is defined as the percent change in Ki-67 expression 
between baseline and C1D15 tumor biopsies observed from each Arm, respectively. 
Descriptive statistics will be provided to evaluate the effects of ARV-471 and anastrozole, 
respectively, on Ki-67 expression in tumors after two weeks of treatment. No comparisons 
between the treatment arms are planned. 
Treatments: ARV-471 (Arm A) and anastrozole (Arm B) 
Population: post-menopausal women with newly diagnosed and treatment naive 
ER+/HER2– breast cancer that is amenable to definitive surgical resection. Participants must 
also have tumor that is at least 1.5 cm by imaging due to biopsy requirements for this study. 
The primary analysis regarding Ki-67 expression will be performed in all enrolled 
participants who received at least one dose of study treatment and had evaluable Ki-67 
measurements from baseline and C1D15 visits. 
Variable: the log-transformed Ki-67 after approximately two weeks of treatment as a 
percentage of the baseline value, ie, the ratio between the Ki-67 measurements obtained from 
C1D15 visit and baseline. 
Intercurrent events: only participants with evaluable Ki-67 results from baseline and 
C1D15 visits will be included in the primary analysis. No participants will be censored or 
excluded due to any reasons other than missing Ki-67 data. 
Population-level summary: the log-transformed percentage Ki-67 will be modelled using a 
GLM. Refer to Section 9.3.2 and the SAP for more details. 
9.1.2.2. Secondary Estimands 
There are no key secondary endpoints defined for this study. No estimands are defined for 
any of the secondary or exploratory endpoints. Statistical analyses for the secondary and 
exploratory endpoints are described in Section 9.3 and in the SAP. 
9.2. Analysis Sets 
For purposes of analysis, the following analysis sets are defined.  
Participant Analysis Set 
Description 
Full Analysis Set  
All enrolled participants who were randomized. Participants are 
analyzed according to the treatment they have been randomized to. 
Safety Analysis Set  
All enrolled participants who receive at least 1 dose of study 
intervention. 
Ki-67 Evaluable Set  
All enrolled participants who were randomized and received at 
least one dose of study treatment and had evaluable Ki-67 
measurements from baseline and C1D15 visits.  


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Participant Analysis Set 
Description 
Pharmacodynamic/Biomarker 
Analysis Set(s) 
The Pharmacodynamic /Biomarker analysis population is defined 
as all enrolled participants with at least 1 of the Pharmacodynamic 
/Biomarkers evaluated at pre and/or post dose. 
Pharmacokinetic Analysis 
set(s) 
PK Concentration Analysis Set 
The PK Concentration Analysis Set includes all participants in the 
Safety Analysis Set who have at least one plasma concentration 
(including those below the limit of quantification) for ARV-471, 
or ARV-473. 
PK Parameter Analysis Set 
The PK Parameter Analysis Set will include all participants in the 
Safety Analysis Set who have at least one PK parameter of interest 
for ARV-471, or ARV-473 (Cmax or AUC).  
PK Pre-Dose Concentration (Ctrough) Analysis Set 
The PK Pre-Dose Concentration Analysis Set will include all 
participants in the Safety Analysis Set who have at least one 
evaluable Ctrough and within the allowable time window following 
treatment for ARV-471 or ARV-473. 
The allowable time window for the PK Pre-Dose sample is defined 
in the following way: 
• 
Dosing time from the day prior to PK sample collection is 
known. 
The allowable time window is the period of time between 
22 hours after dosing on the day prior to the sample 
collection, and 30 minutes after dosing on the day of 
sample collection.  
• 
Dosing time from the day prior is not available.  
The allowable time window is the period of time between 2 hours 
before dosing and 30 minutes after dosing on the day of sample 
collection. 
9.3. Statistical Analyses 
The SAP will be developed and finalized before any analyses are performed and will 
describe the analyses and procedures for accounting for missing, unused, and spurious data. 
This section is a summary of the planned statistical analyses of the primary and secondary 
endpoints. 
9.3.1. General Considerations 
No formal comparisons between ARV-471 and anastrozole or hypotheses testing are planned 
for this study. Descriptive statistics (including point estimates and two-sided CIs) will be 
provided for all parameters of interest. For information purposes, all the 2-sided CIs will be 
reported on both 80% and 95% confidence levels. 
Statistical analyses for the primary and secondary endpoints are summarized below and in 
the SAP.  


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9.3.2. Primary Safety/Efficacy Analyses  
Ki-67 expression will be assessed by immunohistochemical staining in a central laboratory.  
Analysis of Ki-67 reduction will be based on a Ki-67 evaluable population. The 
log-transformed Ki-67 after approximately 2 weeks of treatment as a percentage of the 
baseline value, ie, the ratio between the Ki-67 measurements obtained from C1D15 visit and 
baseline, will be modelled using a GLM, with both stratification factors (ie, baseline Ki-67 
score and the tumor size) and treatment as covariates. Treatment effects for each arm will be 
summarized using the LSM and their two-sided CIs on the log scale. In addition, for easier 
interpretation of the data, the treatment effects will be back transformed and expressed as the 
geometric means and their CIs on the original percentage scale by treatment arm. The percent 
change, in other words, relative reduction, of Ki-67 after 2 weeks of treatment will also be 
reported as the complement of the ratio between the Ki-67 measurement from C1D15 and 
baseline, ie, 100% × (1-Ki-67 from C1D15/Ki-67 from baseline). Similar modeling will be 
applied to ER data.  
9.3.3. Secondary Endpoint(s)/Estimands Analysis 
pCR is defined as no invasive cancer in the breast and sampled axillary lymph nodes 
following completion of neoadjuvant systemic therapy. The rate of pCR will be reported for 
each arm using both point estimates and exact Wilson CIs. Odds ratios between the 
treatments will also be reported using mPEPI score derived from factors assigned a 
numerical score following NET, including Ki67 expression in the surgical specimen, 
pathologic tumor size, and lymph node status. The proportion of participants achieving 
mPEPI score 0 after treatment will be evaluated.  
To support secondary objective of evaluating clinical and pathologic response, binary or 
categorical endpoint such as pathologic stage, pCR, and participants with mPEPI score zero 
at the time of surgical resection (C6D18 ± 14 days), rates of BCS, radiographic response per 
mRECIST in the primary tumor during Cycle 6 will be summarized and the estimated rate 
will be computed by treatment arm along with the exact CI using Wilson method; For 
caliper-based response on C6D1, best percentage change from baseline will be graphed by 
treatment arm. All clinical and pathologic response will be listed for randomized participants 
by treatment arm.  
9.3.4. Tertiary/Exploratory Endpoint(s) 
CCCA at Week 2 is defined as Ki67 score ≤2.7%. An estimate of the difference in the 
observed CCCA rates and corresponding 80% as well as 95% CIs will be calculated. Odds 
ratios between the treatments adjusted for the stratification factors through the 
Cochran-Mantel-Haenszel method will be provided along with their CIs.  
9.3.5. Subgroup Analyses 
Summaries of the primary endpoint will be presented for subgroups defined by the following 
criteria: 
• Size of primary breast tumor (T-stage): ≤2 cm, >2 to <5 cm, or ≥5 cm 


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• Baseline Ki-67 score (assessed locally): <20% vs ≥20% 
Other factors will be considered if the observed data imply potential findings of clinical 
interest. Results of the primary analysis will be reported within each subgroup. Forest plots 
will be provided. 
9.3.6. Other Safety Analyses 
All safety analyses will be performed on the safety population. Descriptive statistics of safety 
will be presented using NCI CTCAE v5.0. All TEAEs, drug-related AEs, SAEs and 
drug-related SAEs will be tabulated using worst grade per NCI CTCAE v5.0 criteria by 
system organ class and MedDRA preferred term. On-study lab parameters including 
hematology, chemistry, liver function, and renal function will be summarized using worst 
grade per NCI CTCAE v5.0 criteria. The extent of exposure including number of doses, 
duration of treatment, and dose modifications will be summarized by treatment arm. A 
summary of deaths with reasons will be provided for all treated participants. 
AEs, ECGs, BP, pulse rate, cardiac monitoring results, and safety laboratory data will be 
reviewed and summarized on an ongoing basis during the study to evaluate the safety of 
participants. Any clinical laboratory, ECG, BP, and pulse rate abnormalities of potential 
clinical concern will be described. Safety data will be presented in tabular and/or graphical 
format and summarized descriptively, where appropriate. 
Medical history and physical examination and neurological examination information, as 
applicable, collected during the study will be considered source data and will not be required 
to be reported, unless otherwise noted. However, any untoward findings identified on 
physical and/or neurological examinations conducted during the active collection period will 
be captured as AEs, if those findings meet the definition of an AE. Data collected at 
screening that are used for inclusion/exclusion criteria, such as laboratory data, ECGs, and 
vital signs, will be considered source data, and will not be required to be reported, unless 
otherwise noted. Demographic data collected at screening will be reported. 
9.4. Sample Size Determination 
There are no plans for formal comparisons between ARV-471 and anastrozole. No power 
calculations are needed. Approximately 150 participants will be randomized to the two 
treatment arms in 2:1 ratio (100 participants to the ARV-471 arm and 50 participants to the 
anastrozole arm). These numbers were chosen to provide meaningful information about the 
primary endpoint, ie, changes (on-treatment C1D15 vs baseline) in Ki-67 expression levels 
after approximately 2 weeks of treatment with ARV-471 and anastrozole, respectively.  
Table 7 and Table 8 provide a list of probable scenarios demonstrating the width of the CIs 
for the primary endpoint under the assumption that 80% (ie, n=120) of the randomized 
participants will provide valid Ki-67 measurements from both their baseline and C1D15 
visits. Table 7 indicates that the width of the 80% CIs of the mean percentage Ki-67 after 
2 weeks of treatment by ARV-471 will not exceed 14% and the width of the 95% CIs will 
not exceed 21.6% if the mean percentage of the corresponding baseline values after 2 weeks 
of treatment ranges from approximately 20% to 40%. The planned sample size will provide 


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estimates for the treatment effect in terms of the reduction of Ki-67 with reasonable 
precision. 
Table 7 
Confidence Intervals for Mean Percentage of Baseline Value in Ki-67 After 
Two Weeks 
Number of 
participants/arma 
Mean 
percentage 
Ki-67 in two 
weeksb 
SD of log- 
transformed 
percent change in 
Ki-67c 
80% CId 
95% CId 
100 (80 evaluable) 
 
20% 
1.0 
(17.3%, 23.1%) 
(16.0%, 25.0%) 
30% 
(26.0%, 34.7%) 
(24.0%, 37.5%) 
40% 
(34.6%, 46.2%) 
(32.0%, 50.0%) 
20% 
1.2 
(16.8%, 23.8%) 
(15.3%, 26.1%) 
30% 
(25.2%, 35.7%) 
(23.0%, 39.2%) 
40% 
(33.6%, 47.6%) 
(30.6%, 52.2%) 
50 (40 evaluable) 
 
20% 
1.0 
(16.3%, 24.6%) 
(14.5%, 27.5%) 
30% 
(24.4%, 36.9%) 
(21.8%, 41.3%) 
40% 
(32.5%, 49.2%) 
(29.1%, 55.1%) 
20% 
1.2 
(15.6%, 25.6%) 
(13.6%, 29.4%) 
30% 
(23.4%, 38.4%) 
(20.4%, 44.0%) 
40% 
(31.2%, 51.2%) 
(27.3% 58.7%) 
a. 
Approximately 100 participants will be enrolled to the ARV-471 arm with 80 participants providing valid Ki-67 
data. Approximately 50 participants will be enrolled to the anastrozole arm with 40 participants providing valid 
Ki-67 data. 
b. 
Percentage Ki-67 in two weeks is defined as the ratio between Ki-67 reported from C1D15 visit and baseline, 
respectively. 
c. 
Ki-67 measurements are assumed to follow a log-normal distribution. The CIs are generated using the quantiles of 
the standard normal distribution on the log scale. Various values for the SD of the log-transformed Ki-67 percent 
change are provided to mimic the variability reported in the coopERA study (Hurvitz 2022a). 
d. 
The CIs are presented in the original percentage scale through exponential-transformation of the Cis generated using 
the log-transformed Ki-67 data. 
 
Table 8 
Confidence Intervals for the Ratio Between the Mean Percentage of Baseline 
Values for Ki-67 Observed from ARV-471 and Anastrozole Arms (Ki-67 
Evaluable Participants N=120) 
Mean 
percentage 
Ki-67 with 
ARV-471a 
Mean 
percentage 
Ki-67 with 
anastrozolea 
SD of log- 
transformed 
percentage 
Ki-67b 
Difference of 
mean 
percentage 
Ki-67 
(anastrozole 
– ARV-471) 
80% CI for the 
ratio of mean 
percentage Ki-67c 
95% CI for the 
ratio of mean 
percentage 
Ki-67c 
20% 
30% 
1.0 
10% 
(1.17, 1.93) 
(1.02, 2.20) 
30% 
40% 
(1.71, 1.04) 
(0.91, 1.96) 
20% 
30% 
1.2 
(1.11, 2.02) 
(0.95, 2.38) 
30% 
40% 
(0.99, 1.80) 
(0.84, 2.11) 
20% 
28% 
1.0 
8% 
(1.09, 1.80) 
(0.95, 2.05) 
30% 
38% 
(0.99, 1.63) 
(0.86, 1.86) 
20% 
28% 
1.2 
(1.04, 1.89) 
(0.88, 2.22) 
30% 
38% 
(0.94, 1.71) 
(0.80, 2.01) 


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20% 
25% 
1.0 
5% 
(0.97, 1.60) 
(0.85, 1.83) 
30% 
35% 
(0.91, 1.50) 
(0.80, 1.71) 
20% 
25% 
1.2 
(0.93, 1.69) 
(0.79, 1.98) 
30% 
35% 
(0.86, 1.57) 
(0.74, 1.85) 
a. 
Assume the relative reduction in Ki-67 attributed to ARV-471 exceeds the reduction attributed to anastrozole by 
5%, 8% and 10% respectively in various scenarios. 
b. 
Assume the same SD for the log- transformed percent change in Ki-67 in either arm. 
c. 
The ratio is defined as the mean percentage Ki-67 with anastrozole divided by the mean percentage Ki-67 with 
ARV-471. A ratio above unity (1) is in favor of ARV-471. 
 


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10. SUPPORTING DOCUMENTATION AND OPERATIONAL CONSIDERATIONS 
10.1. Appendix 1: Regulatory, Ethical, and Study Oversight Considerations 
10.1.1. Regulatory and Ethical Considerations 
This study will be conducted in accordance with the protocol and with the following: 
• Consensus ethical principles derived from international guidelines, including the 
Declaration of Helsinki and CIOMS International Ethical Guidelines; 
• Applicable ICH GCP guidelines; 
• Applicable laws and regulations, including applicable privacy laws. 
The protocol, protocol amendments, ICD, SRSD(s), and other relevant documents 
(eg, advertisements) must be reviewed and approved by the sponsor, submitted to an IRB/EC 
by the investigator, and reviewed and approved by the IRB/EC before the study is initiated. 
Any amendments to the protocol will require IRB/EC approval before implementation of 
changes made to the study design, except for changes necessary to eliminate an immediate 
hazard to study participants. 
Protocols and any substantial amendments to the protocol will require health authority 
approval prior to initiation except for changes necessary to eliminate an immediate hazard to 
study participants. 
The investigator will be responsible for the following: 
• Providing written summaries of the status of the study to the IRB/EC annually or 
more frequently in accordance with the requirements, policies, and procedures 
established by the IRB/EC. 
• Notifying the IRB/EC of SAEs or other significant safety findings as required by 
IRB/EC procedures. 
• Providing oversight of the conduct of the study at the site and adherence to 
requirements of 21 CFR, ICH GCP guidelines, the IRB/EC, applicable European 
regulations, and all other applicable local regulations. 
• After reading the protocol, each Investigator will sign the protocol signature page and 
send a copy of the signed page to the Sponsor or representative. The study will not 
start at any study center at which the Investigator has not signed the protocol. 
10.1.1.1. Reporting of Safety Issues and Serious Breaches of the Protocol or ICH GCP 
In the event of any prohibition or restriction imposed (ie, clinical hold) by an applicable 
regulatory authority in any area of the world, or if the investigator is aware of any new 
information that might influence the evaluation of the benefits and risks of the study 
intervention, the sponsor should be informed immediately.  
In addition, the investigator will inform the sponsor immediately of any urgent safety 
measures taken by the investigator to protect the study participants against any immediate 


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hazard, and of any serious breaches of this protocol or of the ICH GCP that the investigator 
becomes aware of. 
10.1.2. Financial Disclosure 
Investigators and sub-Investigators will provide the Sponsor with sufficient, accurate 
financial information as requested to allow the Sponsor to submit complete and accurate 
financial certification or disclosure statements to the appropriate regulatory authorities. 
Investigators are responsible for providing updated information on financial interests during 
the course of the study and for one year after completion of the study. 
10.1.3. Informed Consent Process 
The investigator or his/her representative will explain the nature of the study, including the 
risks and benefits, to the participant or her legally authorized representative and answer all 
questions regarding the study. The participant or her legally authorized representative should 
be given sufficient time and opportunity to ask questions and to decide whether or not to 
participate in the trial. 
Participants must be informed that their participation is voluntary. Participants or their 
legally authorized representative will be required to sign a statement of informed consent that 
meets the requirements of 21 CFR 50, local regulations, ICH GCP guidelines, privacy and 
data protection requirements, where applicable, and the IRB/EC or study center. 
The investigator must ensure that each study participant or her legally authorized 
representative is fully informed about the nature and objectives of the study, the sharing of 
data related to the study, and possible risks associated with participation, including the risks 
associated with the processing of the participant’s personal data.  
The participant or her legally authorized representative must be informed that his/her 
personal study-related data will be used by the sponsor in accordance with local data 
protection law. The level of disclosure must also be explained to the participant or her legally 
authorized representative. 
The participant or her legally authorized representative must be informed that his/her medical 
records may be examined by Clinical Quality Assurance auditors or other authorized 
personnel appointed by the sponsor, by appropriate IRB/EC members, and by inspectors 
from regulatory authorities. 
The investigator further must ensure that each study participant or her legally authorized 
representative is fully informed about his or her right to access and correct his or her personal 
data and to withdraw consent for the processing of his or her personal data. 
The medical record must include a statement that written informed consent was obtained 
before the participant was enrolled in the study and the date on which the written consent was 
obtained. The authorized person obtaining the informed consent must also sign the ICD. 
Participants or her legally authorized representative must be reconsented to the most current 
version of the ICD(s) during their participation in the study. 


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A copy of the ICD(s) must be provided to the participant or the participant’s legally 
authorized representative. 
A participant who is rescreened is not required to sign another ICD if the rescreening occurs 
within 30 days from the previous ICD signature date. 
10.1.4. Data Protection 
The Sponsor or its representative will not provide individual genotype results to participants, 
any insurance company, any employer, their family members, general physician, or any other 
third party, unless required to do so by law. 
Extra precautions are taken to preserve confidentiality and prevent genetic data being linked 
to the identity of the participant. In exceptional circumstances, however, certain individuals 
might see both the genetic data and the personal identifiers of a participant. For example, in 
the case of a medical emergency, the Sponsor or representative physician or an Investigator 
might know a participant’s identity and also have access to his or her genetic data. Also, 
regulatory authorities may require access to the relevant files. 
All parties will comply with all applicable laws, including laws regarding the implementation 
of organizational and technical measures to ensure protection of participant data. 
Participants’ personal data will be stored at the study site securely to ensure that only 
authorized study staff have access. The study site will implement appropriate technical and 
organizational measures to ensure that the personal data can be recovered in the event of 
disaster. In the event of a potential personal data breach, the study site will be responsible for 
determining whether a personal data breach has in fact occurred and, if so, providing breach 
notifications as required by law. 
To protect the rights and freedoms of participants with regard to the processing of personal 
data, participants will be assigned a single, participant-specific numerical code. Any 
participant records or data sets that are transferred to the sponsor will contain the numerical 
code; participant names will not be transferred. All other identifiable data transferred to the 
sponsor will be identified by this single, participant-specific code. The study site will 
maintain a confidential list of participants who participated in the study, linking each 
participant’s numerical code to his or her actual identity and medical record ID. In case of 
data transfer, the sponsor will protect the confidentiality of participants’ personal data 
consistent with the clinical study agreement and applicable privacy laws. 
10.1.5. Committees Structure 
Please refer to Section 4.4. 
10.1.6. Dissemination of Clinical Study Data 
The results of the study should be reported within one year from the end of the clinical trial. 
Irrespective of the outcome, the Sponsor will submit to the appropriate database a summary 
of the results of the clinical trial within one year from the end of the clinical trial. It shall be 


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accompanied by a summary written in a manner that is understandable to laypersons (where 
applicable). 
10.1.7. Data Quality Assurance 
All participant data relating to the study will be recorded on printed or electronic CRF unless 
transmitted to the sponsor or designee electronically (eg, laboratory data). The investigator is 
responsible for verifying that data entries are accurate and correct by physically or 
electronically signing the CRF. 
The investigator must ensure that the CRFs are securely stored at the study site to prevent 
access by unauthorized third parties. 
The investigator must permit study-related monitoring, audits, IRB/EC review, and 
regulatory agency inspections and provide direct access to source data documents. This 
verification may also occur after study completion. It is important that the investigator(s) and 
their relevant personnel are available during the monitoring visits and possible audits or 
inspections and that sufficient time is devoted to the process. 
Monitoring details describing strategy, including the definition of study critical data items 
and processes (eg, risk-based initiatives in operations and quality, such as risk management 
and mitigation strategies and analytical risk-based monitoring), methods, responsibilities, and 
requirements, including handling of noncompliance issues and monitoring techniques 
(central, virtual, or on-site monitoring), are provided in the Monitoring Plan. 
The sponsor or designee is responsible for the data management of this study, including 
quality checking of the data. 
Records and documents, including signed ICDs, pertaining to the conduct of this study must 
be retained by the investigator for 15 years after study completion unless local regulations or 
institutional policies require a longer retention period. No records may be destroyed during 
the retention period without the written approval of the sponsor. No records may be 
transferred to another location or party without written notification to the sponsor. The 
investigator must ensure that the records continue to be stored securely for as long as they are 
maintained. 
When participant data are to be deleted, the investigator will ensure that all copies of such 
data are promptly and irrevocably deleted from all systems. 
The investigator(s) will notify the sponsor or its agents immediately of any regulatory 
inspection notification in relation to the study. Furthermore, the investigator will cooperate 
with the sponsor or its agents to prepare the investigator site for the inspection and will allow 
the sponsor or its agent, whenever feasible, to be present during the inspection. The 
investigator site and investigator will promptly resolve any discrepancies that are identified 
between the study data and the participant’s medical records. The investigator will promptly 
provide copies of the inspection findings to the sponsor or its agent. Before response 
submission to the regulatory authorities, the investigator will provide the sponsor or its 
agents with an opportunity to review and comment on responses to any such findings. 


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10.1.8. Source Documents 
Source documents provide evidence for the existence of the participant and substantiate the 
integrity of the data collected. Source documents are filed at the investigator site. 
Data reported on the CRF or entered in the eCRF that are from source documents must be 
consistent with the source documents or the discrepancies must be explained. The 
investigator may need to request previous medical records or transfer records, depending on 
the study. Also, current medical records must be available. 
The investigator must maintain accurate documentation (source data) that supports the 
information entered in the CRF. Source data should be attributable, legible, 
contemporaneous, original, accurate, and complete. Changes to source data should be 
traceable, should not obscure the original entry, and should be explained if necessary (eg, via 
an audit trail). 
Study monitors will perform ongoing source data verification to confirm that data entered 
into the CRF by authorized site personnel are accurate, complete, and verifiable from source 
documents; that the safety and rights of participants are being protected; and that the study is 
being conducted in accordance with the currently approved protocol and any other study 
agreements, the ICH GCP guidelines, and all applicable regulatory requirements. 
10.1.9. Study and Site Start and Closure 
The study start date is the date on which the clinical study will be open for recruitment of 
participants. 
The first act of recruitment is the date of the first participant’s first visit and will be the study 
start date. 
Criteria for Stopping the Study 
The sponsor designee reserves the right to close the study site or terminate the study at any 
time for any reason at the sole discretion of the sponsor. Study sites will be closed upon study 
completion. A study site is considered closed when all required documents and study 
supplies have been collected and a study-site closure visit has been performed. 
The investigator may initiate study-site closure at any time upon notification to the sponsor 
or designee if requested to do so by the responsible IRB/EC or if such termination is required 
to protect the health of study participants. 
Reasons for the early closure of a study site by the sponsor may include but are not limited 
to: 
• Failure of the investigator to comply with the protocol, the requirements of the 
IRB/EC or local health authorities, the sponsor’s procedures, or the ICH GCP 
guidelines; 
• Inadequate recruitment of participants by the investigator; 


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• Discontinuation of further study intervention development. 
If the study is prematurely terminated or suspended, the sponsor shall promptly inform the 
investigators, the Ecs/IRBs, the regulatory authorities, and any CRO(s) used in the study of 
the reason for termination or suspension, as specified by the applicable regulatory 
requirements. The investigator shall promptly inform the participant and should assure 
appropriate participant therapy and/or follow-up. 
Study termination is also provided for in the clinical study agreement. If there is any conflict 
between the contract and this protocol, the contract will control as to termination rights. 
10.1.10. Publication Policy 
If publication is addressed in the clinical study agreement, the publication policy set out in 
this section will not apply. 
The data generated by this study are confidential information of the Sponsor. The publication 
policy with respect to the Investigator and study center will be set forth in the Clinical Trial 
Agreement. 
The results of this study may be published or presented at scientific meetings. The 
Investigator agrees to submit all manuscripts or abstracts to the Sponsor before submission.  
The Sponsor will comply with the requirements for publication of study results. In 
accordance with standard editorial and ethical practice, the Sponsor will generally support 
publication of multicenter studies only in their entirety and not as individual study center 
data. In this case, a Coordinating Investigator will be designated by mutual agreement. 
Authorship will be determined by mutual agreement and in line with International Committee 
of Medical Journal Editors authorship requirements.  
10.1.11. Sponsor’s Qualified Medical Personnel 
The contact information for the sponsor’s appropriately qualified medical personnel for the 
study is documented in the study contact list. 
To facilitate access to appropriately qualified medical personnel for study related medical 
questions or problems, participants are provided with an ECC at the time of informed 
consent. The ECC contains, at a minimum, (a) protocol and study intervention identifiers, 
(b) participant’s study identification number, (c) site emergency phone number active 
24 hours/day, 7 days per week, and (d) the sponsor Call Center number. 
The ECC is intended to augment, not replace, the established communication pathways 
between the investigator, site staff, and study team. The ECC is to be used by healthcare 
professionals not involved in the research study only, as a means of reaching the investigator 
or site staff related to the care of a participant. The sponsor Call Center number should only 
be used when the investigator and site staff cannot be reached. The sponsor Call Center 
number is not intended for use by the participant directly; if a participant calls that number 
directly, he or she will be directed back to the investigator site. 












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terminology and the same AE term should be used on both the CRF and the SAE Report 
Form for reporting of SAE information. 
Safety Event 
Recorded on the CRF 
Reported on the SAE 
Report Form to Pfizer 
Safety Within 24 Hours 
of Awareness 
SAE 
All 
All 
Nonserious AE 
All 
None 
Exposure to the study 
intervention under study 
during pregnancy or 
breastfeeding  
All AEs/SAEs associated 
with EDP or breastfeeding 
 
Note: Instances of EDP or 
EDB not associated with an 
AE or SAE are not captured 
in the CRF. 
All instances of EDP are 
reported (whether or not 
there is an associated 
SAE)* 
All instances of EDB are 
reported (whether or not 
there is an associated 
SAE). ** 
Environmental or 
occupational exposure 
to the product under 
study to a non-
participant (not 
involving EDP or EDB). 
None. Exposure to a study 
non-participant is not 
collected on the CRF. 
The exposure (whether or 
not there is an associated 
AE or SAE) must be 
reported.*** 
* 
EDP (with or without an associated AE or SAE): any pregnancy information is reported to the 
sponsor using SAE Report Form and EDP Supplemental Form; if the EDP is associated with an SAE, 
then the SAE is reported to the sponsor using the SAE Report Form.  
**  EDB is reported to the sponsor using the SAE Report Form which would also include details of 
any SAE that might be associated with the EDB.  
*** Environmental or Occupational exposure: AEs or SAEs associated with occupational 
exposure are reported to the sponsor using the SAE Report Form. 
• When an AE or SAE occurs, it is the responsibility of the investigator to review all 
documentation (eg, hospital progress notes, laboratory reports, and diagnostic 
reports) related to the event. 
• The investigator will then record all relevant AE or SAE information in the CRF. 
• It is not acceptable for the investigator to send photocopies of the participant’s 
medical records to the sponsor in lieu of completion of the SAE Report Form/AE or 
SAE CRF page. 
• There may be instances when copies of medical records for certain cases are 
requested by the sponsor. In this case, all participant identifiers, with the exception of 
the participant number, will be redacted on the copies of the medical records before 
submission to the sponsor. 






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RUSSIAN 
FEDERATION: 
Armenia, Azerbaijan, 
Belarus, Georgia, 
Kazakhstan, 
Kyrgyzstan, Mongolia, 
Tajikistan, 
Turkmenistan, 
Uzbekistan 
GEORGIA 
SPAIN: Andorra 
SPAIN 
UNITED STATES: 
American Samoa, 
Guam, Northern 
Mariana Islands, 
Puerto Rico, United 
States Virgin Islands 
and United States 
Minor Outlying Islands 
UNITED 
STATES 
Detailed instructions regarding the SAE submission process are to be found in the 
Investigator folder provided to each site. 
The Investigator, or designated party, should notify the appropriate IRB/EC of SAEs 
occurring at the study site and other AE reports received from the Sponsor, in 
accordance with local procedures and statutes. 
The Investigator, or designated party, should notify the appropriate IRB/EC of SAEs 
occurring at the study site and other AE reports received from the Sponsor, in 
accordance with local procedures and statutes. 
 
 


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10.4. Appendix 4: Contraceptive and Barrier Guidance  
All participants enrolled in this study will be post-menopausal females as defined in 
Section 5.1, and thus contraceptive and barrier guidance does not apply.


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10.5. Appendix 5: Genetics 
Not applicable to this study. 


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10.6. Appendix 6: Liver Safety: Suggested Actions and Follow-Up Assessments  
Potential Cases of Drug Induced liver Injury 
Humans exposed to a drug who show no sign of liver injury (as determined by elevations in 
transaminases) are termed “tolerators,” while those who show transient liver injury but adapt 
are termed “adaptors.”  In some participants, transaminase elevations are a harbinger of a 
more serious potential outcome. These participants fail to adapt and therefore are 
“susceptible” to progressive and serious liver injury, commonly referred to as DILI. 
Participants who experience a transaminase elevation above 3 × ULN should be monitored 
more frequently to determine if they are “adaptors” or are “susceptible.” 
In the majority of DILI cases, elevations in AST and/or ALT precede Tbili elevations 
(>2 × ULN) by several days or weeks. The increase in Tbili typically occurs while AST/ALT 
is/are still elevated above 3 × ULN (ie, AST/ALT and Tbili values will be elevated within the 
same laboratory sample). In rare instances, by the time Tbili elevations are detected, 
AST/ALT values might have decreased. This occurrence is still regarded as a potential DILI. 
Therefore, abnormal elevations in either AST or ALT in addition to Tbili that meet the 
criteria outlined below are considered potential DILI (assessed per Hy’s law criteria) cases 
and should always be considered important medical events, even before all other possible 
causes of liver injury have been excluded. 
The threshold of laboratory abnormalities for a potential DILI case depends on the 
participant’s individual baseline values and underlying conditions. Participants who present 
with the following laboratory abnormalities should be evaluated further as potential DILI 
(Hy’s law) cases to definitively determine the etiology of the abnormal laboratory values: 
Participants with AST/ALT and Tbili baseline values within the normal range who 
subsequently present with AST or ALT values >3 × ULN AND a Tbili value >2 × ULN with 
no evidence of hemolysis and an alkaline phosphatase value <2 × ULN or not available. 
For participants with baseline AST or ALT or Tbili values above the ULN, the following 
threshold values are used in the definition mentioned above, as needed, depending on which 
values are above the ULN at baseline: 
Preexisting AST or ALT baseline values above the normal range: AST or ALT values 
>2 times the baseline values AND >3 × ULN; or >8 × ULN (whichever is smaller). 
Preexisting values of Tbili above the normal range: Tbili level increased from baseline value 
by an amount of at least 1 × ULN or if the value reaches >3 × ULN (whichever is smaller). 
Rises in AST/ALT and Tbili separated by more than a few weeks should be assessed 
individually based on clinical judgment; any case where uncertainty remains as to whether it 
represents a potential Hy’s law case should be reviewed with the sponsor.  
The participant should return to the investigator site and be evaluated as soon as possible, 
preferably within 48 hours from awareness of the abnormal results. This evaluation should 


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include laboratory tests, detailed history, and physical assessment. The possibility of hepatic 
neoplasia (primary or secondary) should be considered.  
In addition to repeating measurements of AST and ALT and Tbili for suspected Hy’s law 
cases, additional laboratory tests should include albumin, creatine kinase, direct and indirect 
bilirubin, GGT, PT/INR, total bile acids, and alkaline phosphatase. Consideration should also 
be given to drawing a separate tube of clotted blood and an anticoagulated tube of blood for 
further testing, as needed, for further contemporaneous analyses at the time of the recognized 
initial abnormalities to determine etiology. A detailed history, including relevant information, 
such as review of ethanol, acetaminophen/paracetamol (either by itself or as a coformulated 
product in prescription or over-the-counter medications), recreational drug, or supplement 
(herbal) use and consumption, family history, sexual history, travel history, history of contact 
with a jaundiced person, surgery, blood transfusion, history of liver or allergic disease, and 
potential occupational exposure to chemicals, should be collected. Further testing for acute 
hepatitis A, B, C, D, and E infection, liver imaging (eg, biliary tract), and collection of serum 
samples for acetaminophen/paracetamol drug and/or protein adduct levels may be warranted.  
All cases demonstrated on repeat testing as meeting the laboratory criteria of AST/ALT and 
Tbili elevation defined above should be considered potential DILI (Hy’s law) cases if no 
other reason for the LFT abnormalities has yet been found. Such potential DILI (Hy’s law) 
cases are to be reported as SAEs, irrespective of availability of all the results of the 
investigations performed to determine etiology of the LFT abnormalities.  
A potential DILI (Hy’s law) case becomes a confirmed case only after all results of 
reasonable investigations have been received and have excluded an alternative etiology. 




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• At the discretion of the investigator, any arrhythmia classified as an adverse 
experience. 
The enumerated list of major events of potential clinical concern are recommended as “alerts” or 
notifications from the core ECG laboratory to the investigator and sponsor, and not to be considered as 
all-inclusive of what to be reported as AEs/SAEs. 
 


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10.8. Appendix 8: Prohibited Concomitant Medications That May Result in DDI 
Participants should not receive the following while participating in trials with ARV-471 
(unless utilized with caution to treat a drug-related AE when no alternative is available).  
Note: These lists are examples and are not intended to be exhaustive. 
• Examples of sensitive P-gp substrates and P-gp substrates with narrow therapeutic 
indices: 
P-gp substrates with 
narrow therapeutic 
indices:  
dabigatran etexilate, digoxin, fexofenadine, apixaban, rivaroxaban 
• Examples of strong CYP3A4 inhibitors and inducers  
Strong CYP3A4 
inhibitors:  
boceprevir, cobicistat, danoprevir and ritonavir, elvitegravir and 
ritonavir, grapefruit juice, indinavir and ritonavir, itraconazole, 
ketoconazole, lopinavir and ritonavir, paritaprevir and ritonavir 
and (ombitasvir and/or dasabuvir), posaconazole, ritonavir, 
saquinavir and ritonavir, telaprevir, tipranavir and ritonavir, 
telithromycin, troleandomycin, voriconazole clarithromycin, 
idelalisib, nefazodone, nelfinavir  
Strong CYP3A 
inducers:  
apalutamide, carbamazepine, enzalutamide, mitotane, phenytoin, 
rifampin, St. John’s wort  
• Examples of known QT prolonging drugs: 
Known QT prolonging 
drugs:  
aclarubicin, amiodarone, anagrelide, arsenic trioxide, astemizole, 
azithromycin, bepridil, cesium chloride, chloroquine, 
chlorpromazine, chlorprothixene, cilostazol, ciprofloxacin, 
cisapride, citalopram, clarithromycin, cocaine, disopyramide, 
dofetilide, domperidone, donepezil, dronedarone, droperidol, 
erythromycin, escitalopram, flecainide, fluconazole, gatifloxacin, 
grepafloxacin, halofantrine, haloperidol, hydroquinidine, 
hydroxychloroquine, ibogaine, ibutilide, levolfoxacin, 
levomepromazine (methotrimeprazine, levomethdyl acetate, 
levosulpiride, meglumine antimoniate, mesoridazine, methadone, 
moxifloxacin, nifekalant, ondansetron, oxaliplatin, papaverine 
HCl (Intracoronary), pentamidine, pimozide, probucol, 
procainamide, propofol, quinidine, roxithromycin, sertindole, 
sevoflurane, sotalol, sparfloxacin, sulpiride, sultopride, 
terfenadine, terlipressin, terodiline, thioridazine, vandetanib 
 


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References:  
Examples of sensitive P-gp substrates and those with narrow therapeutic indices  
• https://www.fda.gov/drugs/drug-interactions-labeling/drug-development-and-drug-
interactions-tablesubstrates-inhibitors-and-inducers   
o Table 5-1: Examples of clinical substrates for transporters (for use in clinical DDI 
studies and/or drug labeling) (12/03/2019)  
Examples of Strong CYP3A4 inhibitors (eg, itraconazole) and inducers (eg, rifampin)  
• https://drug-interactions.medicine.iu.edu/MainTable.aspx   
• https://www.fda.gov/drugs/drug-interactions-labeling/drug-development-and-drug-
interactions-tablesubstrates-inhibitors-and-inducers   
o Table 3-2: Examples of clinical inhibitors for P450-mediated metabolisms (for 
concomitant use clinical DDI studies and/or drug labeling) (03/06/2020)   
o Table 3-3: Examples of clinical inducers for P450-mediated metabolisms (for 
concomitant use clinical DDI studies and/or drug labeling) (12/03/2019)  
Examples of known QC prolonging drugs  
• https://www.crediblemeds.org/index.php   
 
 


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10.9. Appendix 9: Alternative Measures During Public Emergencies  
The alternative study measures described in this section are to be followed during public 
emergencies, including the COVID-19 pandemic. This appendix applies for the duration of 
the COVID-19 pandemic globally and will become effective for other public emergencies 
only upon written notification from the sponsor.  
Use of these alternative study measures are expected to cease upon the return of business as 
usual circumstances (including the lifting of any quarantines and travel bans/advisories).  
10.9.1. Eligibility  
While SARS-CoV2 testing is not mandated for this study, local clinical practice standards for 
testing should be followed. A participant should be excluded if he/she has a positive test 
result for SARS-CoV2 infection, is known to have asymptomatic infection, or is suspected of 
having SARS-CoV2. Participants with active infections are excluded from study 
participation as per exclusion criteria, (Section 5.2). When the infection resolves, the 
participant may be considered for re-screening.  
10.9.2. Telehealth Visits 
The use of Video TeleMed Visits during public emergencies will be acceptable in the 
following cases: 
Visits where only AE assessment and routine blood samples, which may be performed 
locally, are required and the results are received and reviewed by the Investigator prior to the 
TeleMed visit with the participant. 
Visits occurring on Day 1 of Cycle 3 and beyond may be done via TeleMed if the participant 
did not have any significant toxicities requiring re-assessment at the previous in-person visit 
and has not reported any new significant toxicity in the interim. The same requirement for 
receiving and reviewing laboratory results as noted in the previous bullet point also apply in 
this case. 
Other study visits should be maintained as in-person clinic visits unless local, governmental, 
or other restrictions are in place that prohibit travel or in-person clinic visits. In such cases, 
the Sponsor should be advised in advance, where possible, that a TeleMed visit will be used. 
The use of alternate or local labs and/or imaging centers is allowed at the discretion of the 
Investigator. Use of an alternate imaging center should have Sponsor approval prior to use. 
Study participants must be reminded to promptly notify site staff about any change in their 
health status.  
10.9.3. Study Intervention 
Participants who cannot be seen in clinic due to quarantine requirements or other limitations 
due to public health emergencies may receive IP shipped, utilizing a secure delivery method 
with signature required, directly to their home address. The site is to confirm receipt of the 


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shipment with the participant, document participant compliance and the need for direct 
shipment to the participant. 
10.9.4. Adverse Events and Serious Adverse Events 
If a participant has COVID-19 during the study, this should be reported as an AE or SAE and 
appropriate medical intervention provided.  
10.9.5. Treatment for COVID While on Study 
If a participant tests positive for COVID and has respiratory or other symptoms requiring 
medical intervention or hospitalization, ARV-471 or anastrozole is to be discontinued. All 
participants may receive any available therapy to treat their symptoms, including treatments 
authorized by the FDA for emergency use for COVID-19. Clear documentation must be 
provided in the participant’s medical record and their eCRF regarding all therapy received as 
well as all AEs related to COVID and its treatment. 
10.9.6. Guidance for COVID vaccine administration 
10.9.6.1. For Participants Who Have Not Initiated Study Treatment  
It is recommended that they should receive the second dose of vaccine at least five days prior 
to initiation of study treatment. In addition, they should have completely recovered from any 
side effects related to administration of the vaccine before starting study treatment. 
10.9.6.2. For Participants Already on Study Treatment and Beyond Cycle 1  
Participants who are already receiving study treatment and beyond Cycle 1, may receive the 
vaccine as it becomes available to them. Please carefully document any AEs that occur 
related to the vaccine administration and advise the Sponsor of any significant reactions that 
occur. 
 
 


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10.10. Appendix 10: Eastern Cooperative Oncology Group Performance Status 
Developed by the Eastern Cooperative Oncology Group (ECOG), Robert L. Comis, MD, 
Group Chair  
GRADE 
ECOG PERFORMANCE STATUS 
0 
Fully active, able to carry on all pre-disease performance without restriction 
1 
Restricted in physically strenuous activity but ambulatory and able to carry out work 
of a light or sedentary nature, eg, light housework, office work 
2 
Ambulatory and capable of all selfcare but unable to carry out any work activities; up 
an about more than 50% of waking hours 
3 
Capable of only limited selfcare; confined to bed or chair more than 50% of waking 
hours 
4 
Completely disabled; cannot carry on any selfcare; totally confined to bed or chair 
5 
Dead 
Oken M, Creech R, Tormey D. Toxicity and response criteria of the Eastern Cooperative Oncology Group. Am J Clin Oncol. 
1982;5:649-655. 
 


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10.11. Appendix 11: Radiological Imaging Assessment: modified RECIST 1.1 
The antitumor activity of study treatment will be assessed according to modified RECIST 1.1 
adapted from Eisenhauer 2009. Breast tumor imaging will be performed following the SOA, 
tumor imaging data will be entered into the CRF and tumor imaging response derived per 
modified RECIST 1.1 as described in this appendix. RECIST 1.1 modifications are outlined 
in Table 10. 
Consistent imaging methods must be used for all imaging visits for the same participant.  
Table 10 
RECIST 1.1 Modifications 
Requirement 
RECIST 1.1 
Modified RECIST 1.1 
Reasoning 
Imaging Modality  
Contrast enhanced 
CT/MRI body imaging 
Contrast enhanced breast 
MRI 
Breast Ultrasound 
Breast Mammography 
Study protocol is assessing 
treatment effect on breast 
cancer primary tumor 
Measurable Disease 
Non-nodal disease 
minimum size is 10 mm 
in the longest diameter 
Lesions can be 
identified from all 
organ groups 
Primary breast lesion 
minimum size is 1.5 cm (15 
mm) in the longest diameter 
Additional lesions identified 
on breast imaging (meeting 
RECIST 1.1 criteria) may be 
identified and followed as 
target lesions  
Study protocol is assessing 
treatment effect on breast 
cancer primary tumor and 
required imaging is breast 
imaging 
Non-measurable 
Disease 
Lesions can be 
identified from all 
organ groups 
Lesions identified on breast 
imaging that do not meet 
target lesion criteria 
Study protocol is assessing 
treatment effect on breast 
cancer primary tumor and 
required imaging is breast 
imaging 
Irradiated lesions 
Previously irradiated 
lesions may be 
identified as a 
measurable lesion if the 
lesion demonstrates 
progressive disease 
Exclusion criteria prohibits 
prior radiation treatment 
Protocol exclusion criteria 
10.11.1. Imaging Requirements 
Radiographic imaging (eg, breast ultrasound, breast MRI with contrast, and/or mammogram) 
is required during Screening, C4D1, and within 7 days prior to surgical resection. Contrast 
enhanced breast MRI is the preferred imaging modality. The same imaging method used at 
baseline must also be used at all post baseline imaging visits (eg. C4D1, within 7 days prior 
to surgical resection and any unscheduled imaging visits performed to assess the primary 
breast tumor). A change in imaging technique (ie, modality) could result in lesion status 
being not evaluable. 
Breast imaging conducted as part of the participant’s routine clinical management (eg, 
ultrasound, MRI, mammogram) and obtained before signing of the ICD may be utilized for 
Screening or baseline purposes provided the procedures met the protocol-specified criteria 
and were performed within the time frame defined in the SoA (Section 1.3).  


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The primary breast tumor must be measurable with a size of at least 1.5 cm (15 mm) in the 
longest diameter. Tumor imaging response assessment will be performed according to 
mRECIST 1.1 criteria. 
During, or prior to screening, full staging scans may be performed, if necessary, at the 
discretion of the investigator as per SOC. Any identified lesions may be followed as a non-
target lesion with consistent repeat imaging.  
10.11.2. Modified RECIST 1.1 Disease Assessment  
10.11.2.1. Measurable Lesions at Baseline 
Measurable Lesions: Lesions identified on breast imaging that can be accurately measured in 
at least 1 dimension, are reproducible and represent study disease. 
• Primary breast lesion with a minimum measurement of 1.5 cm (15 mm) in the longest 
diameter measurement 
• A non-nodal (not primary breast tumor) lesion that can be accurately measured at 
baseline with a minimum measurement of 10 mm in the longest diameter 
measurement and is suitable for accurate repeated measurements. 
• A pathological (malignant) lymph node that can be accurately measured at baseline 
with a minimum measurement of 15 mm in the short axis measurement are 
considered measurable and assessable as target lesions. 
• If imaging is breast MRI and MRI slice thickness is more than 5 mm, the minimum 
size of measurable disease at baseline should be twice the slice thickness of the 
baseline scan. Up to 5 lesions per organ type (eg, breast tissue, lymph nodes, chest 
wall) may be recorded. 
• Soft tissue component of bone may be identified as target lesion if the soft tissue 
component measurement is at least 10 mm (the lesion must be in a location that will 
be included in the field of view on subsequent breast imaging). 
10.11.2.2. Nontarget Lesions at Baseline 
Non measurable disease includes all other lesions, (or sites of disease) identified on breast 
imaging not recorded as target lesion as well as non-nodal lesions that are too small to be 
considered measurable and truly non measurable lesions that represent study disease, such as 
pathological lymph nodes with short axis measurement between 10 mm and 14.9 mm, chest 
wall disease and/or osseous bone lesions. 
Lesions identified on staging standard of care imaging may be entered as non-target lesion 
and followed for response assessment. 
10.11.2.3. Normal Sites of Disease 
Cystic lesions: Simple cysts should not be considered as malignant lesions and should not be 
recorded either as target or non-target disease. Cystic lesions thought to represent cystic 
metastases can be measurable lesions if they meet the specific definition above. If non-cystic 
lesions are also present, these are preferred as target lesions. 


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Normal nodes: lymph nodes with short axis <10 mm are considered normal and should not 
be recorded or followed either as measurable or as non-measurable disease. 
10.11.2.4. Recording Modified RECIST 1.1 Tumor Assessments 
All sites of disease should be assessed at baseline. Baseline assessments should be done as 
close as possible to the start of study treatment and within 28 days prior randomization. If 
baseline assessment is inadequate or missing, subsequent statuses generally should be 
recorded as not evaluable until progressive disease is identified. 
Target Lesions 
Target lesions should be selected based on size (longest lesions) and suitability for accurate 
repeated measurements. The site and location of each target lesion will be recorded as well as 
the longest diameter for each non-nodal lesion and the shot axis diameter for each 
pathological lymph node that meet the size criteria for a target lesion. The SOD of the target 
lesions at baseline will be the basis for comparison to post baseline imaging assessments and 
the post baseline SOD. 
Target lesions will be assessed post baseline for lesion status and measurements recorded. 
The SOD will be compared to baseline SOD and to nadir (smallest SOD on study) SOD to 
derive the target lesion response (see Table 11).  
Post-Baseline Target Lesion Special Considerations: 
• Actual measurements for target lesion (nodal and non-nodal) should continue to be 
recorded (including nodes that have reduced to normal size).  
• Target lesions (nodal and non-nodal) that are too small to measure should be 
considered as a default value of 5 mm.  
• Target lesions (nodal and non-nodal) that are considered to have disappeared should 
be recorded as 0 mm (including nodes that are no longer visible on imaging).  
• If a target lesion cannot be measured accurately due to it being too large, provide an 
estimate of the size of the lesion. 
• If a target lesion disappears (or reduces to normal size for lymph node) and reappears 
at a subsequent time point, the lesion should continue to be measured and included in 
the SOD. In the event that all target lesions achieved CR status, the lesion 
reappearance would be considered as progressive disease at the time of reappearance.  
• If 2 or more target lesions coalesce (merge), the measurement of the coalesced mass 
is recorded and used in the SOD. 
• If a large target lesion splits into 2 or more parts, each part is recorded, and the sum of 
the parts is used in the SOD. 
• When a target lesion has had any intervention (ie, radiotherapy, embolization, 
surgery) during the study, the size of the target lesion should still be provided when 
possible. If the invention results in the target lesion measurement not possible, the 
target lesion should be identified as Not Evaluable. 


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• If one or more target lesion is Not Evaluable, and the sum of diameters meets the 
criteria for progressive disease, progressive disease overrides not evaluable as the 
target lesion response.  
• Target lesion response of progressive disease requires 20% increase in the SOD of all 
target lesions AND a minimum absolute increase of 5 mm in the SOD. 
Non-Target Disease 
NTLs will be identified at baseline. Measurements are not required for these lesions, but their 
status will be followed at post baseline visits.  
At each post-baseline visit the NTL status (ie, Present, Absent, Not Evaluable, Not Assessed) 
will inform the NTL response. To achieve ‘unequivocal progression’ on the basis of 
non-target lesions, there must be an overall level of substantial worsening in non-target 
disease such that, even in presence of SD or PR in target lesions, the overall tumor burden 
has increased sufficiently to merit discontinuation of treatment. A modest ‘increase’ in the 
size of one or more non-target lesions is usually not sufficient to qualify for unequivocal 
progression status. See Table 12 for NTL overall response at each assessment. 
New Lesions 
At each post baseline visit, imaging will be assessed for any new lesions. Details of any new 
lesions will also be recorded with the date of assessment and lesion location/description. The 
presence of one or more new lesions is assessed as progressive disease. A lesion identified at 
a follow up assessment in an anatomical location that was not scanned at baseline is 
considered a new lesion and will indicate disease progression.  
The finding of a new lesion should be unequivocal: ie, not attributable to differences in 
scanning technique, change in imaging modality or findings thought to represent something 
other than tumor.  
If a new lesion is equivocal, for example because of its small size, the treatment and tumor 
assessments should be continued until the new lesion has been confirmed. If repeat scans 
confirm there is a new lesion, then the progression date should be declared using the date of 
the initial scan. 
10.11.3. Disease Response Status at Each Imaging Assessment 
The timepoint assessment will include deriving the Target Lesion Response, Non Target 
Lesion Response and the Overall Response based on the lesion status of the target, non-target 
and/or new lesions assessed at the post-baseline imaging visit.  
For target lesion response of Complete Response/Partial Response, imaging must be 
evaluable, with all anatomy covered, and with no target lesion with status of Not 
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10.11.3.1. Target Disease Response Status 
Target lesion response definitions for each imaging assessment: 
Complete Response (CR) 
Complete disappearance of all target lesions with the exception of 
nodal disease. All target lymph nodes must decrease to normal size 
(short axis <10 mm).  
Partial Response (PR) 
At least a 30% decrease in the sum of the diameters of TL, taking as 
reference the baseline sum of diameters 
Stable (SD) 
Neither sufficient shrinkage to qualify for PR nor sufficient increase 
to qualify for PD 
Progressive Disease (PD) 
At least a 20% increase in the sum of diameters of target lesions, 
taking as reference the smallest sum on study (this includes the 
baseline sum if that is the smallest on study).  
In addition to the relative increase of 20%, the sum must also 
demonstrate an absolute increase of at least 5mm. 
Not Evaluable (NE) 
If the SOD does not derive PD, and: 
• One or more of the target lesions have not been assessed; OR 
• One or more target lesion cannot be measured accurately due to poor 
technical quality; OR 
• One or more target lesions were excised or irradiated and have not 
reappeared or increased; OR 
• Imaging modality or assessment method is inconsistent with baseline 
assessment 
10.11.3.2. Nontarget Disease Response Status 
NTL response definitions for each imaging assessment:  
Complete Response (CR) 
Disappearance of all NTL since baseline. All lymph nodes must be 
non-pathological in size (<10 mm short axis). 
Non-Complete 
Response/Non-Progressive 
Disease 
Persistence of one or more non target lesions 
Progressive Disease (PD) 
Unequivocal progression of existing NTL. Unequivocal progression 
may be due to progression in one lesion only or in several lesions. 
Generally, the overall tumor burden must increase sufficiently to 
merit discontinuation of therapy. 
Not Evaluable (NE) 
An overall non-target assessment cannot be made at this visit based 
on one or more of the following: 
• One or more of the NTL have not been assessed; OR 
• One or more NTL cannot be assessed due to poor technical quality; 
OR 
• One or more NTL were excised or irradiated and have not reappeared 
or increased; OR 


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• Imaging modality or assessment method is inconsistent with baseline 
assessment and impacts the ability to accurately assess the disease 
status 
10.11.3.3. New Lesions 
The appearance of any new unequivocal malignant lesion indicates disease progression. If a 
new lesion is equivocal, for example due to its small size, continued assessment will clarify 
the etiology. If repeat assessments confirm the lesion, then progression should be recorded on 
the date of the initial assessment. A lesion identified in an area not previously scanned will 
be considered a new lesion. 
New lesion definition for each imaging assessment: 
Yes 
Definitely present 
No 
Not present, or uncertain 
10.11.3.4. Overall Response at Each Imaging Assessment  
Table 11 
RECIST 1.1 Overall Response at Each Assessment  
Target Lesions 
Non-Target Lesions 
New Lesions 
Overall Response 
CR 
CR 
No 
CR 
CR 
NA 
No 
CR 
NA 
CR 
No 
CR 
CR 
Non-CR/Non-PD 
No 
PR 
CR 
NE 
No 
PR 
PR 
Non-PD, NE 
No 
PR 
SD 
Non-PD, NE 
No 
SD 
NE 
Non-PD, NE 
No 
NE 
PD 
Any 
Yes or No 
PD 
Any 
PD 
Yes or No 
PD 
Any 
Any 
Yes 
PD 
NA 
Non-CR/Non-PD 
No 
Non-CR/Non-PD 
NA 
NA 
No 
NED 
NA 
NE 
No 
NE 
CR=complete response; PD=progressive disease; PR=partial response; SD=stable disease; NE=not evaluable/not all 
assessed/missing; NED=no evidence of disease (relevant when no TL and NTL at baseline); NA=Not Applicable 
(relevant when no TL and/or NTL at baseline); NTL=non-target lesion; TL=target lesion 


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Table 12 
Non-Target Disease Only RECIST 1.1 Overall Response at Each Assessment 
Non-Target Lesions 
New Lesions 
Overall Response 
CR 
No 
CR 
Non-CR/Non-PD 
No 
Non-CR/Non-PD 
NE 
No 
NE 
Unequivocal Progressive Disease 
Yes or No 
PD 
Any 
Yes 
PD 
CR=complete response; PD=progressive disease; NE=Not Evaluable/Not Assessed 


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10.12. Appendix 12: Abbreviations 
The following is a list of abbreviations used in the protocol. 
Abbreviation 
Term 
AE 
adverse event 
AI 
aromatase inhibitor 
AIDS 
acquired immunodeficiency syndrome 
AJCC 
American Joint Committee on Cancer 
ALT 
alanine aminotransferase 
Alk Phos 
alkaline phosphatase 
ANC 
absolute neutrophil count 
aPTT 
activated partial thromboplastin time 
ASCO 
American Society of Clinical Oncology 
AST 
aspartate aminotransferase 
AUC 
area under the curve 
AV 
atrioventricular 
BCRP 
breast cancer resistance protein 
BCS 
breast conserving surgery 
BP 
blood pressure 
bpm 
beats per minute 
BUN 
blood urea nitrogen 
C 
Cycle 
C1D1 
Cycle 1 Day 1 
CAP 
College of American Pathologists 
CBR 
clinical benefit response 
CCCA 
complete cycle cell arrest 
CDK 
cyclin-dependent kinase 
CFR 
Code of Federal Regulations 
CI 
confidence interval 
CIOMS 
Council for International Organizations of Medical Sciences 
CK1α 
casein kinase 1α 
Cmax 
maximum observed concentration 
Cmin 
minimum observed concentration 
CNS 
central nervous system 
CONSORT 
Consolidated Standards of Reporting Trials 
COVID 
coronavirus disease 
CRF 
case report form 
CR 
complete response 
CRO 
contract research organization 
CT 
computerized tomography 
CTCAE 
Common Terminology Criteria for Adverse Events 
Ctrough 
trough concentration 
CYP 
cytochrome P450 
D 
Day 
DC50 
half-maximal degradation concentration 


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Abbreviation 
Term 
DDI 
drug-drug interaction 
DILI 
drug-induced liver injury 
DLT 
dose-limiting toxicity 
DNA 
deoxyribonucleic acid 
DSU 
drug safety unit 
EC 
ethics committee 
ECC 
emergency contact card 
ECG 
electrocardiogram 
ECOG 
Eastern Cooperative Oncology Group 
eCRF 
electronic case report form 
EDB 
exposure during breastfeeding 
EDP 
exposure during pregnancy 
ER 
estrogen receptor 
ER+ 
estrogen receptor positive 
EU 
European Union 
EudraCT 
European Clinical Trials Database 
FDA 
Food and Drug Administration (United States) 
FIH 
first-in-human 
FSH 
follicle-stimulating hormone 
GCP 
Good Clinical Practice 
GGT 
gamma-glutamyl transferase 
GI 
gastrointestinal 
GI50 
half-maximal growth inhibition 
GLM 
generalized linear model 
GLP 
good laboratory practices 
GSPT1 
G1 to S Phase Transition 1 gene 
HBV 
hepatitis B virus 
HCV 
hepatitis C virus 
HER2 
human epidermal growth factor receptor 2 
HIV 
human immunodeficiency virus 
HR+ 
hormone receptor positive 
IB 
investigator’s brochure 
IC50 
half-maximal inhibitory concentration 
ICD 
informed consent document 
ICH 
International Council for Harmonisation 
ID 
identification 
IHC 
immunohistochemistry 
IND 
investigational new drug 
INR 
international normalized ratio 
IP 
investigational product 
IRB 
institutional review board 
IRT 
interactive response technology 
LFT 
liver function test 
LSM 
least square means 


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Abbreviation 
Term 
MAD 
maximum administered dose 
MedDRA 
Medical Dictionary for Regulatory Activities 
mPEPI 
modified Pre-Operative Endocrine Prognostic Index 
mRECIST 
modified Response Evaluation Criterion in Solid Tumors  
MRI 
magnetic resonance imaging 
MTD 
maximum tolerated dose 
NA 
not applicable 
NCI 
National Cancer Institute 
NE 
not evaluable/not all assessed/missing 
NED 
no evidence of disease (relevant when no TL and NTL at baseline) 
NET 
neoadjuvant endocrine therapy 
NOAEL 
no-observed-adverse-effect level 
NOD/SCID 
nonobese diabetic/severe combined immunodeficiency 
NTL 
non-target lesion 
nsAI 
nonsteroidal aromatase inhibitor 
ORR 
objective response rate 
pCR 
pathologic complete response 
PD 
pharmacodynamics(s) 
P-gp 
p-glycoprotein 
PgR 
progesterone receptor 
PK 
pharmacokinetic(s) 
PO 
oral(ly) 
POC 
proof of concept 
PPI 
proton pump inhibitor 
PR 
partial response 
PROTAC 
PROteolysis Targeting Chimera 
PS 
performance status 
PT 
prothrombin time 
PTT 
partial thromboplastin time 
PVC 
premature ventricular contraction/complex 
QD 
every day 
QTc 
corrected QT 
QTcF 
corrected QT (Fridericia method) 
RECIST 
Response Evaluation Criteria in Solid Tumors 
RNA 
ribonucleic acid 
RP2D 
recommended phase 2 dose 
SAE 
serious adverse event 
sAI 
steroidal aromatase inhibitor 
SAP 
statistical analysis plan 
SARS-CoV2 
severe acute respiratory syndrome coronavirus 2 
SD 
standard deviation 
SERD 
selective estrogen receptor downregulator 
SmPC 
summary of product characteristics 
SoA 
schedule of activities 


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Abbreviation 
Term 
SOC 
standard of care 
SOD 
sum of the diameters 
SRC 
safety review committee 
SRSD 
single reference safety document 
SUSAR 
suspected unexpected serious adverse reaction 
t1/2 
terminal elimination half-life 
Tbili 
total bilirubin 
TEAE 
treatment-emergent adverse event 
TGI 
tumor growth inhibition 
TRAE 
treatment-related adverse event 
TNM 
tumor, node, metastasis 
ULN 
upper limit of normal 
US 
United States 
USPI 
United States Prescribing Information 
WBC 
white blood cell 
 


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CONFIDENTIAL 
Page 110 
 
10.13. Appendix 13: Protocol Amendment History 
The Protocol Amendment Summary of Changes Table for the current amendment is located 
directly before the TOC. The protocol amendment summary of changes tables for past 
amendments can be found below: 
 Amendment to Original Protocol (14 Dec 2022) 
Overall Rationale for the Amendment: Updates made 
 
 
Section # 
and Name 
Description of Key 
Changes 
Brief Rationale 
Substantial or 
Nonsubstantial 
Appendix 
12.1: 
 
Requirements 
Addition of Appendix 12.1: 
 Requirements 
• 
Addition of suggestion for 
bone mineral density 
testing due to anastrozole 
lowering circulating 
estrogen levels 
• 
Details added regarding co-
administration of PPIs and 
H2 blockers. The 
concomitant use of PPIs 
with ARV-471 is not 
recommended. H2 blockers 
(eg, cimetidine, famotidine) 
or local antacids (eg, 
aluminum hydroxide, 
calcium carbonate, bismuth 
subsalicylate) may be used. 
Clarification that only 
participants for whom 
neoadjuvant endocrine 
monotherapy is deemed 
appropriate are eligible  
• Exclusion criteria now to 
exclude patients with rare 
hereditary problems of 
galactose intolerance, the 
Lapp lactase deficiency or 
glucose-galactose 
malabsorption. 
 
 
Nonsubstantial 
 




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10.14.2. Investigator Acknowledgment 
PROTOCOL TITLE: 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  
PROTOCOL NO: ARV-471-BC-201 
VERSION: Global Amendment #1 
This protocol is a confidential communication of Arvinas Estrogen Receptor, Inc. I confirm 
that I have read this protocol, I understand it, and I will work according to this protocol. I 
will also work consistently with the ethical principles that have their origin in the Declaration 
of Helsinki and that are consistent with Good Clinical Practices and the applicable laws and 
regulations. Acceptance of this document constitutes my agreement that no unpublished 
information contained herein will be published or disclosed without prior written approval 
from the Sponsor. 
Instructions to the Investigator: Please SIGN and DATE this signature page. PRINT your 
name, title, and the name of the study center in which the study will be conducted. Return the 
signed copy to Arvinas Estrogen Receptor, Inc. 
 
I have read this protocol in its entirety and agree to conduct the study accordingly: 
 
Signature of Investigator:  
Date:  
 
Printed Name:  
 
Investigator Title:  
 
 
Name/Address of Center:  
 


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receptor-rich stage 2 to 3 breast cancer: clinical and biomarker outcomes and predictive value 
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Goss PE, Ingle JN, Pritchard KI, et al. Exemestane versus anastrozole in postmenopausal 
women with early breast cancer: NCIC CTG MA.27-a randomized controlled phase III trial. 
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Gradishar WJ, Moran MS, Abraham J, et al. NCCN Guidelines® Insights: Breast Cancer, 
Version 4.2021: Featured Updates to the NCCN Guidelines. Journal of the National 
Comprehensive Cancer Network. 2021 May 1;19(5):484-93. 
Guerrero-Zotano AL, Arteaga CL. Neoadjuvant trials in ER+ breast cancer: a tool for 
acceleration of drug development and discovery. Cancer Discovery. 2017 Jun;7(6):561-74. 
Hamilton E, Vahdat L, Han HS, et al. First-in-human safety and activity of ARV-471, a 
novel PROTAC estrogen receptor degrader, in ER+/HER2- locally advanced or metastatic 
breast cancer. Cancer Res. 2022;82(4_suppl). 
Howell A, Cuzick J, Baum M, et al; ATAC Trialists' Group. Results of the ATAC 
(Arimidex, Tamoxifen, Alone or in Combination) trial after completion of 5 years' adjuvant 
treatment for breast cancer. Lancet. 2005 Jan 1-7;365(9453):60-2. 
Hurvitz SA, Martin M, Press MF, et al. Potent Cell-Cycle Inhibition and Upregulation of 
Immune Response with Abemaciclib and Anastrozole in neoMONARCH, Phase II 
Neoadjuvant Study in HR+/HER2- Breast Cancer. Clin Cancer Res. 2020 Feb 1;26(3):566-
580. doi: 10.1158/1078-0432.CCR-19-1425. 
Hurvitz SA, Quiroga V, Park YH, et al. Neoadjuvant giredestrant (GDC-9545) + palbociclib 
versus anastrozole + palbociclib in postmenopausal women with estrogen receptor-positive, 
HER2-negative, untreated early breast cancer: Primary analysis of the randomized, open-
label, phase II coopERA breast cancer study. San Antonio Breast Cancer Symposium 2021. 
Cancer Res 15 February 2022a; 82 (4_Supplement): PD13–06. 
Hurvitz SA, Schott AF (Presenter), Ma C, et al. ARV-471, a PROTAC® ER degrader in 
advanced ER-positive/human epidermal growth factor receptor 2 (HER2)-negative breast 


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cancer: phase 2 expansion (VERITAC) of a phase 1/2 study. San Antonio Breast Cancer 
Symposium 2022. 08 December 2022b; Presentation GS3-03. 
Johnston SRD, Harbeck N, Hegg R, et al. Abemaciclib Combined With Endocrine Therapy 
for the Adjuvant Treatment of HR+, HER2-, Node-Positive, High-Risk, Early Breast Cancer 
(monarchE). J Clin Oncol. 2020 Dec 1;38(34):3987-3998. 
Juric D, Ciruelos EM, Rubovszky G, et al. Alpelisib (ALP)+ fulvestrant (FUL) for advanced 
breast cancer (ABC): Phase 3 SOLAR-1 trial results. In San Antonio Breast Cancer 
Symposium (SABCS) (Abstract # GS3-08) on December 2018 Dec 4 (Vol. 6). 
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and targeted therapy for breast cancer: ASCO guideline. Journal of clinical oncology: official 
journal of the American Society of Clinical Oncology. 2021 May 1;39(13):1485-505. 
Kuter I, Gee JM, Hegg R, Singer CF, et al. Dose-dependent change in biomarkers during 
neoadjuvant endocrine therapy with fulvestrant: results from NEWEST, a randomized Phase 
II study. Breast Cancer Research and Treatment. 2012 May;133(1):237-46. 
Lerebours F, Rivera S, Mouret‐Reynier MA, et al. Randomized phase 2 neoadjuvant trial 
evaluating anastrozole and fulvestrant efficacy for postmenopausal, estrogen receptor–
positive, human epidermal growth factor receptor 2–negative breast cancer patients: Results 
of the UNICANCER CARMINA 02 French trial (UCBG 0609). Cancer. 2016 
Oct;122(19):3032-40. 
Li Y, Yang D, Yin X, et. al. Clinicopathological Characteristics and Breast Cancer–Specific 
Survival of Patients With Single Hormone Receptor–Positive Breast Cancer. JAMA Netw 
Open. 2020;3(1):e1918160. 
Lindeman GJ, Bowen R, Jerzak KJ, et al. Results from VERONICA: A randomized, phase II 
study of second-/third-line venetoclax (VEN)+ fulvestrant (F) versus F alone in estrogen 
receptor (ER)-positive, HER2-negative, locally advanced, or metastatic breast cancer 
(LA/MBC). American Society of Clinical Oncology Annual Meeting 2021.  
Ma CX, Suman VJ, Leitch AM, et al. ALTERNATE: Neoadjuvant endocrine treatment 
(NET) approaches for clinical stage II or III estrogen receptor-positive HER2-negative breast 
cancer (ER+ HER2– BC) in postmenopausal (PM) women: Alliance A011106 2020.  
Martí C, Sánchez-Méndez JI. The present and future of neoadjuvant endocrine therapy for 
breast cancer treatment. Cancers (Basel). 2021;13(11):2538. 
Quenel-Tueux N, Debled M, Rudewicz J, et al. Clinical and genomic analysis of a 
randomised phase II study evaluating anastrozole and fulvestrant in postmenopausal patients 
treated for large operable or locally advanced hormone-receptor-positive breast cancer. 
British Journal of Cancer. 2015 Aug;113(4):585-94. 


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Robertson JF, Nicholson RI, Bundred NJ, et al. Comparison of the short-term biological 
effects of 7alpha-[9-(4,4,5,5,5-pentafluoropentylsulfinyl)-nonyl]estra-1,3,5, (10)-triene-
3,17beta-diol (Faslodex) versus tamoxifen in postmenopausal women with primary breast 
cancer. Cancer Res. 2001;61(18):6739-6746. 
Robertson JF, Dixon JM, Sibbering DM, et al. A randomized trial to assess the biological 
activity of short-term (pre-surgical) fulvestrant 500 mg plus anastrozole versus fulvestrant 
500 mg alone or anastrozole alone on primary breast cancer. Breast Cancer Research. 2013 
Apr;15(2):1-0. 
Robertson JF, Evans A, Henschen S, et al. A randomized, window of opportunity study 
comparing the effects of the novel oral SERD AZD9496 with fulvestrant in patients with 
ER+ HER2-primary breast cancer. Clin Cancer Res. 2020 Aug 15;26(16):4242-4249 
Smith IE, Dowsett M, Ebbs SR, et al. Neoadjuvant treatment of postmenopausal breast 
cancer with anastrozole, tamoxifen, or both in combination: the Immediate Preoperative 
Anastrozole, Tamoxifen, or Combined with Tamoxifen (IMPACT) multicenter double-blind 
randomized trial. J Clin Oncol. 2005 Aug 1;23(22):5108-16. 
Smith I, Yardley D, Burris H, et al. Comparative Efficacy and Safety of Adjuvant Letrozole 
Versus Anastrozole in Postmenopausal Patients With Hormone Receptor-Positive, Node-
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Anastrozole Clinical Evaluation (FACE) Trial. J Clin Oncol. 2017 Apr 1;35(10):1041-1048. 
Smith IE, Robertson J, Kilburn L, et al. Long-term outcome and prognostic value of Ki67 
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3 trial. Lancet Oncol 2020; 21: 1443–54. 
Spring LM, Gupta A, Reynolds KL, et al. Neoadjuvant endocrine therapy for estrogen 
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Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA CANCER J CLIN 
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development and cancer. Gene. 2016;584:111-119. 
The Breast International Group (BIG) 1-98 Collaborative Group. A Comparison of Letrozole 
and Tamoxifen in Postmenopausal Women with Early Breast Cancer. N Engl J Med 2005; 
353:2747-2757. 
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positive breast cancers undergoing different types of neoadjuvant therapy: a meta-analysis. 
BMC Women's Health. 2020 Dec;20(1):1-1. 

SAP_001.pdf: 
Protocol No: ARV-471-BC-201
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
Statistical Analysis Plan
Version: Draft 3.0
Date: 15 November 2024




                          Protocol No.:
ARV-471-BC-201
                               Version:
Final 3.0
                                  Date:
15Nov2024 
Statistical Analysis Plan
3
Table of Contents
SIGNATURE PAGE .................................................................................................................2
Table of Contents.......................................................................................................................3
ABBREVIATIONS ...................................................................................................................8
1
Introduction ......................................................................................................................10
2
Study Design.....................................................................................................................10
2.1
Study Objectives, Endpoints, and Estimands ..............................................................10
2.1.1
Study Objectives and Endpoints...........................................................................10
2.1.2
Estimands .............................................................................................................11
2.2
Sample Size Considerations.........................................................................................12
3
Analysis Sets.....................................................................................................................13
4
General Considerations.....................................................................................................14
4.1
Programming Environment..........................................................................................14
4.2
General Statistical Methods.........................................................................................14
4.2.1
Analysis Groups ...................................................................................................14
4.2.2
Descriptive Summaries.........................................................................................14
4.2.3
Presentation Conventions .....................................................................................14
4.3
Covariates and Strata ...................................................................................................15
4.4
Subgroups ....................................................................................................................15
4.5
Multiple Comparison/Multiplicity...............................................................................15
5
Definitions & Data Handling Conventions ......................................................................15
5.1
Study Day, Duration, and Study Periods .....................................................................15
5.1.1
Study Day .............................................................................................................15
5.1.2
Duration................................................................................................................16
5.2
Analysis Visit Windows ..............................................................................................16
5.3
Baseline and Change from Baseline ............................................................................16
5.4
Missing Data................................................................................................................16
5.4.1
Partial or Missing Dates and Time .......................................................................16
5.4.2
Other Missing Values...........................................................................................16
6
STUDY POPULATION AND DISPOSITION ...............................................................17
6.1
Analysis Sets................................................................................................................17
6.2
Participant Disposition.................................................................................................17


                          Protocol No.:
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                               Version:
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                                  Date:
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Statistical Analysis Plan
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6.3
Protocol Deviations......................................................................................................17
7
Demographics And Disease Characteristics.....................................................................18
7.1
Demographics and Baseline Characteristics................................................................18
7.2
Disease Staging and Disease Characteristics...............................................................18
7.3
Disease Staging at Post-Surgery..................................................................................19
7.4
Molecular Biology of Disease at Baseline...................................................................20
7.5
Prior Cancer Related Surgery/Biopsy..........................................................................20
7.6
Medical History ...........................................................................................................21
8
Protocol-Required Drug Exposure And Compliance .......................................................21
9
Prior and Concomitant Therapies.....................................................................................22
9.1
Prior and Concomitant Medications ............................................................................22
10
Efficacy Analyses.............................................................................................................22
10.1
Assessment...................................................................................................................22
10.1.1
Tumor Biopsies ....................................................................................................22
10.1.2
Radiographic Imaging ..........................................................................................22
10.1.3
Physical Exam ......................................................................................................22
10.1.4
Local Pathological Assessments...........................................................................23
10.2
Definitions of Efficacy Endpoints ...............................................................................23
10.2.1
Ki-67 Percentage at C1D15 (Primary) .................................................................23
10.2.2
ER Percentage at C1D15......................................................................................23
10.2.3
pCR Rate ..............................................................................................................23
10.2.4
mPEPI Score and mPEPI0 Rate ...........................................................................23
10.2.5
Breast Conserving Surgery (BCS) Rate ...............................................................24
10.2.6
Radiographic Response per mRECIST in Primary Tumor during Cycle 6..........24
10.2.7
Caliper-Based Response.......................................................................................24
10.2.8
CCCA Rate...........................................................................................................24
10.3
Analysis of Efficacy Variables ....................................................................................24
10.3.1
Ki-67 Percentage at C1D15 (Primary) .................................................................24
10.3.2
Binary or Categorical Endpoints ..........................................................................25
10.3.3
Primary Tumor Assessments................................................................................25
10.3.4
ER AQUA Score Percentage at C1D15 and Surgery...........................................25
10.3.5
PR H-score Percentage at C1D15 and Surgery ....................................................26


                          Protocol No.:
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                               Version:
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                                  Date:
15Nov2024 
Statistical Analysis Plan
5
10.3.6
Subgroup Analyses...............................................................................................26
11
Safety Analyses ................................................................................................................26
11.1
Adverse Events ............................................................................................................27
11.2
Deaths ..........................................................................................................................28
11.3
Vital Signs....................................................................................................................28
11.4
Clinical Laboratory ......................................................................................................28
11.5
12-Lead Electrocardiogram .........................................................................................29
11.6
Eastern Cooperative Oncology Group (ECOG) Performance Status ..........................29
12
Other Analyses .................................................................................................................29
12.1
Pharmacokinetics .........................................................................................................29
12.2
Pharmacodynamics ......................................................................................................30
13
Schedule of Analyses........................................................................................................30
14
References ........................................................................................................................30


                          Protocol No.:
ARV-471-BC-201
                               Version:
Final 3.0
                                  Date:
15Nov2024 
Statistical Analysis Plan
6
MODIFICATION HISTORY
DRAFT VERSION HISTORY
Draft 0.1
09Jan2023
The first draft based on Original Protocol 
dated on 27 May 2022
Draft 0.1
27Jan2023
Update based on Amendment #1 dated on 09 
Jan 2023 and comments from internal 
reviewer
Draft 0.2
10Mar2023
Update based on Arvinas comments
Draft 0.3
17Apr2023
* Accept Arvinas updates and Caidya updates 
in draft 0.2
* Remove the summary for BOR and ORR, 
add summary for radiographic response per 
mRECIST in primary tumor during Cycle 6 
*  Update based on Arvinas comments on 
TFL shells   
Draft 0.4
24Apr2023
Correct Typo
Final 1.0
25Apr2023
N/A
Draft 1.1
16Jan2024
Update based on Arvinas comments on dryrun 
TFLs
Draft 1.2
24May2024
Update based on Arvinas comments and new 
requests
Final 2.0
03June2024
Accept the updates in version 1.2 and make 
minor updates based on Arvinas comments
Draft 2.1
06Sep2024
Update CI round rules and baseline definition
Add Estimands in the document
Draft 2.2
11Oct2024
Update based on the comments on dryrun #2
draft: 
* Update the definition of subgroups –
derivation will be from primary target 
lesion(s) and laboratory data instead of IRT
* Add summary for participants with Tumor 
Biopsies at each visit, medical history, 
absolute dose intensity, relative dose intensity, 
subgroup analysis for change of tumor size by 
baseline tumor size category 


                          Protocol No.:
ARV-471-BC-201
                               Version:
Final 3.0
                                  Date:
15Nov2024 
Statistical Analysis Plan
7
* Add additional plots for KI-67 at surgery, 
ER AQUA Score, PR H-score
* Update Concomitant Medications and 
TEAE definition
Draft 2.3
14Nov2024
Accept the updates in version 2.2 and the edits 
by Arvinas in version 2.2
Update based on the comments on dryrun #2 
final: 
* update ‘MedDRA 24.0’ to ‘MedDRA 27.0
or higher’
* Tornado plot for treatment emergent adverse 
events with Grade 3 or higher by Preferred 
Term
* Add imputation for PR H-score post-baseline 
value of 0 for the derivation of log transform 
analysis
Final 3.0
15Nov2024
Accept update in 2.3


                          Protocol No.:
ARV-471-BC-201
                               Version:
Final 3.0
                                  Date:
15Nov2024 
Statistical Analysis Plan
8
ABBREVIATIONS
AE 
adverse event 
ALT 
alanine aminotransferase 
Alk Phos 
alkaline phosphatase 
AST 
aspartate aminotransferase 
AUC 
area under the curve 
BCS
breast conserving surgery
BID 
twice daily 
BP 
blood pressure 
CBR 
clinical benefit response 
CCCA
complete cycle cell arrest 
CI 
confidence interval 
Cmax 
maximum observed concentration 
Cmin 
minimum observed concentration 
CRF
case report form
CTCAE 
Common Terminology Criteria for Adverse Events 
Ctrough 
trough concentration 
ECG 
electrocardiogram 
ECOG 
Eastern Cooperative Oncology Group 
EDC
electronic data capture
ER
estrogen receptor 
HER2 
human epidermal growth factor receptor 2 
IHC 
immunohistochemistry 
ISH
in situ hybridization
LSM 
least square means 
MedDRA 
Medical Dictionary for Regulatory Activities 
mPEPI 
modified Pre-Operative Endocrine Prognostic Index 
MRI 
magnetic resonance imaging 
NA 
not applicable 
NCI 
National Cancer Institute 
NET 
neoadjuvant endocrine therapy 
ORR 
objective response rate 
pCR 
pathologic complete response 
PD 
pharmacodynamics(s) 
PK 
pharmacokinetic(s) 
PR 
partial response 
PT 
preferred term
QTc 
corrected QT 
QTcF 
corrected QT (Fridericia method) 
mRECIST 
modified Response Evaluation Criteria in Solid Tumors 
SAE 
serious adverse event 
SAP 
statistical analysis plan 
SD 
Stable Disease 
SOC 
standard of care 


                          Protocol No.:
ARV-471-BC-201
                               Version:
Final 3.0
                                  Date:
15Nov2024 
Statistical Analysis Plan
9
t1/2 
terminal elimination half-life 
Tbili 
total bilirubin 
TEAE 
treatment-emergent adverse event 
Tmax 
time to maximum concentration 
TRAE 
treatment-related adverse event 
ULN 
upper limit of normal 


                          Protocol No.:
ARV-471-BC-201
                               Version:
Final 3.0
                                  Date:
15Nov2024 
Statistical Analysis Plan
10
1
INTRODUCTION
The objective of this document is to detail the statistical methodology to be used in the 
summary and the final statistical analysis of clinical study protocol ARV-471-BC-201: “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”. 
This SAP is based on Protocol dated on 09 Jan 2023 and Case Report Forms (CRFs) dated on 
23 Aug 2023. 
2
STUDY DESIGN
This is a Phase 2, open-label, randomized, non-comparative, proof of concept study of ARV-
471 or anastrozole in participants with ER+/HER2– breast cancer amenable to definitive 
surgical resection. The main goal of this study is to evaluate the biological activity of ARV-
471 and anastrozole, respectively.
Participants will be randomized in a 2:1 manner to receive treatment on one of two treatment 
arms for approximately 5.5 months:
x
Arm A: ARV-471 200 mg orally, daily and continuously until day before surgical 
resection (no later than C6D18 + 14 days)
x
Arm B: anastrozole 1 mg orally, daily and continuously until day before surgical 
resection (no later than C6D18 + 14 days)
Stratification will occur based on the following features of the participant’s breast cancer:
x
Size of primary breast tumor (T-stage): ≤ 2 cm, > 2 to < 5 cm, or ≥ 5 cm. 
x
Ki-67 score (assessed locally): < 20% or ≥ 20% 
Participants will have a screening biopsy, an on-treatment biopsy on C1D15 (+ 5 days), and 
surgical resection approximately 5.5 months after starting treatment (C6D18 ± 14 days). 
Participants will return for follow up 30 days (+ 7 days) after definitive surgical resection. 
After surgery, participants will receive SOC radiation and systemic therapy (chemotherapy, 
endocrine therapy, etc.) in accordance with local practice guidelines per the treating 
physician’s discretion. No participant should take study drug dispensed for the trial after 
surgical resection, and no study drug should be dispensed after surgical resection.
2.1
Study Objectives, Endpoints, and Estimands
2.1.1
Study Objectives and Endpoints
Objective 
Endpoints 
Primary 
Evaluate the effects of ARV-471 and 
anastrozole, respectively, on Ki-67 
expression in tumors after 2 weeks of 
treatment
Percent change in Ki-67 expression between 
baseline and C1D15 tumor biopsies 
Secondary 


                          Protocol No.:
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Statistical Analysis Plan
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Evaluate the safety and tolerability of ARV-
471 and anastrozole, respectively 
Incidence of all adverse events, serious 
adverse events, and adverse events leading to 
study drug discontinuation 
Evaluate the clinical and pathological 
response of ARV-471 and anastrozole, 
respectively 
Pathologic stage, pathologic complete 
response (pCR)rate, and modified Pre-
operative Endocrine Prognostic Index 
(mPEPI) score at the time of surgical resection 
(C6D18 ± 14 days); rates of breast conserving 
surgery (BCS); radiographic response of the 
primary tumor based on breast imaging during 
cycle 6; caliper-based response on C6D1 
Exploratory 
Evaluate the effects of ARV-471 and 
anastrozole, respectively, on CCCA after 2 
weeks of treatment 
CCCA (Ki67 ≤2.7%) rates at C1D15 
Evaluate ER degradation of ARV-471 
Percent change in estrogen receptor (ER)
protein levels between baseline and C1D15 
Evaluate the effects of ARV-471 and 
anastrozole, respectively, on Ki-67, and ER 
degradation by ARV-471 in tumors at the 
time of surgical resection. 
Changes in ER and Ki-67 expression between 
baseline and Cycle 6 surgical tumor samples; 
Rates of CCCA in the Cycle 6 surgical 
samples. 
Explore additional biomarkers that may be 
associated with the effects of ARV-471 in 
tumor tissue 
Additional biomarkers may include, but are 
not limited to, PgR expression, 
 
 
Correlate exposure of ARV-471 with ER 
reduction 
Correlate population PK model-derived PK 
parameters (AUC, Cmin, Cmax) with ER 
reduction or other response parameters 
2.1.2
Estimands
2.1.2.1 Primary Estimands
The primary estimand of this study is defined as the percent change in Ki-67 expression 
between baseline and C1D15 tumor biopsies observed from each Arm, respectively. 
Descriptive statistics will be provided to evaluate the effects of ARV-471 and anastrozole, 
respectively, on Ki-67 expression in tumors after two weeks of treatment. No comparisons 
between the treatment arms are planned.
Treatments: ARV-471 (Arm A) and anastrozole (Arm B)
Population: post-menopausal women with newly diagnosed and treatment naïve ER+/HER2–
breast cancer that is amenable to definitive surgical resection. Participants must also have 
tumor that is at least 1.5 cm by imaging due to biopsy requirements for this study. The 
primary analysis regarding Ki-67 expression will be performed in all enrolled participants 
who received at least one dose of study treatment and had evaluable Ki-67 measurements 
from baseline and C1D15 visits.


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Variable: the log-transformed Ki-67 after approximately two weeks of treatment as a 
percentage of the baseline value, ie, the ratio between the Ki-67 measurements obtained from 
C1D15 visit and baseline.
Intercurrent events: only participants with evaluable Ki-67 results from baseline and C1D15 
visits will be included in the primary analysis. No participants will be censored or excluded 
due to any reasons other than missing Ki-67 data.
Population-level summary: the log-transformed percentage Ki-67 will be modelled using a 
GLM. Refer to Protocol Section 9.3.2 and the SAP for more details.
2.1.2.2 Secondary Estimands
There are no key secondary endpoints defined for this study. No estimands are defined for 
any of the secondary or exploratory endpoints. 
2.2
Sample Size Considerations
There are no plans for formal comparisons between ARV-471 and anastrozole. No power 
calculations are needed. Approximately 150 participants will be randomized to the two 
treatment arms in 2:1 ratio (100 participants to the ARV-471 arm and 50 participants to the 
anastrozole arm). These numbers were chosen to provide meaningful information about the 
primary endpoint, ie, changes (on-treatment C1D15 vs baseline) in Ki-67 expression levels 
after approximately 2 weeks of treatment with ARV-471 and anastrozole, respectively. 
Table 1 and Table 2 provide a list of probable scenarios demonstrating the width of the CIs 
for the primary endpoint under the assumption that 80% (ie, n=120) of the randomized 
participants will provide valid Ki-67 measurements from both their baseline and C1D15 
visits. Table 2 indicates that the width of the 80% CIs of the mean percentage Ki-67 after 2 
weeks of treatment by ARV-471 will not exceed 14% and the width of the 95% CIs will not 
exceed 21.6% if the mean percentage of the corresponding baseline values after 2 weeks of 
treatment ranges from approximately 20% to 40%. The planned sample size will provide 
estimates for the treatment effect in terms of the reduction of Ki-67 with reasonable 
precision. 
Table 1 Confidence Intervals for Mean Percentage of Baseline Value in Ki-67 After Two Weeks
Number of 
participants/arm a
Mean 
percentage 
Ki-67 in 
two weeks b
SD of log-
transformed 
percent 
change in Ki-
67 c
80% CI d
95% CI d
100 (80 evaluable)
20%
1.0
(17.3%, 23.1%) 
(16.0%, 25.0%) 
30%
(26.0%, 34.7%) 
(24.0%, 37.5%) 
40%
(34.6%, 46.2%) 
(32.0%, 50.0%) 
20%
1.2
(16.8%, 23.8%) 
(15.3%, 26.1%) 
30%
(25.2%, 35.7%)
(23.0%, 39.2%)
40%
(33.6%, 47.6%) 
(30.6%, 52.2%) 
50 (40 evaluable)
20%
1.0
(16.3%, 24.6%) 
(14.5%, 27.5%) 
30%
(24.4%, 36.9%) 
(21.8%, 41.3%) 
40%
(32.5%, 49.2%) 
(29.1%, 55.1%) 


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Statistical Analysis Plan
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Number of 
participants/arm a
Mean 
percentage 
Ki-67 in 
two weeks b
SD of log-
transformed 
percent 
change in Ki-
67 c
80% CI d
95% CI d
20%
1.2
(15.6%, 25.6%) 
(13.6%, 29.4%) 
30%
(23.4%, 38.4%) 
(20.4%, 44.0%) 
40%
(31.2%, 51.2%) 
(27.3% 58.7%) 
a. Approximately 100 participants will be enrolled to the ARV-471 arm with 80 participants providing valid Ki-
67 data. Approximately 50 participants will be enrolled to the anastrozole arm with 40 participants providing 
valid Ki-67 data. 
b. Percentage Ki-67 in two weeks is defined as the ratio between Ki-67 reported from C1D15 visit and baseline 
respectively. 
c. Ki-67 measurements are assumed to follow a log-normal distribution. The CIs are generated using the 
quantiles of the standard normal distribution on the log scale. Various values for the SD of the log-transformed 
Ki-67 percent change are provided to mimic the variability reported in the coopERA study (Hurvitz 2022).
d. The CIs are presented in the original percentage scale through exponential-transformation of the CIs 
generated using the log-transformed Ki-67 data. 
Table 2 Confidence Intervals for the Ratio Between the Mean Percentage of Baseline Values for Ki-67 
Observed from ARV-471 and Anastrozole Arms (Ki-67 Evaluable Participants N=120)
Mean 
percentage 
Ki-67 with 
ARV-471 a
Mean 
percentage 
Ki-67 with 
anastrozole a
SD of log-
transformed 
percentage 
Ki-67 b
Difference of mean 
percentage Ki-67 
(anastrozole –
ARV-471) 
80% CI for the ratio 
of mean percentage 
Ki-67 c
95% CI for the 
ratio of mean 
percentage Ki-67 c
20%
30%
1.0
10%
(1.17, 1.93) 
(1.02, 2.20) 
30%
40%
(1.71, 1.04) 
(0.91, 1.96) 
20%
30%
1.2
(1.11, 2.02) 
(0.95, 2.38) 
30%
40%
(0.99, 1.80) 
(0.84, 2,11) 
20%
28%
1.0
8%
(1.09, 1.80) 
(0.95, 2.05) 
30%
38%
(0.99, 1.63) 
(0.86, 1.86) 
20%
28%
1.2
(1.04, 1.89) 
(0.88, 2.22) 
30%
38%
(0.94, 1.71) 
(0.80, 2.01) 
20%
25%
1.0
5%
(0.97, 1.60) 
(0.85, 1.83) 
30%
35%
(0.91, 1.50) 
(0.80, 1.71) 
20%
25%
1.2
(0.93, 1.69) 
(0.79, 1.98) 
30%
35%
(0.86, 1.57) 
(0.74, 1.85) 
a. Assume the relative reduction in Ki-67 attributed to ARV-471 exceeds the reduction attributed to anastrozole 
by 5%, 8% and 10% respectively in various scenarios. 
b. Assume the same SD for the log- transformed percent change in Ki-67 in either arm. 
c. The ratio is defined as the mean percentage Ki-67 with anastrozole divided by the mean percentage Ki-67 
with ARV-471. A ratio above unity (1) is in favor of ARV-471. 
3
ANALYSIS SETS
For purposes of analysis, the following analysis sets are defined.
Analysis Set 
Description 
Full Analysis Set 
All enrolled participants who were randomized. Participants are 
analyzed according to the treatment they have been randomized to. 


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Safety Analysis Set 
All enrolled participants who receive at least 1 dose of study 
intervention. 
Ki-67 Evaluable Set 
All enrolled participants who were randomized and received at 
least one dose of study treatment and had evaluable Ki-67 
measurements other than ‘0’ or ‘< 1’ from baseline and evaluable 
Ki-67 measurements from C1D15 visits. 
Pharmacodynamic/ 
Biomarker Analysis 
Set(s) 
The Pharmacodynamic/Biomarker analysis population is defined as 
all enrolled participants with at least 1 of the Pharmacodynamic/
Biomarkers evaluated at pre and/or post dose. 
PK Concentration 
Analysis Set
The PK Concentration Analysis Set includes all participants in the 
Safety Analysis Set who have at least one plasma concentration 
(including those below the limit of quantification) for ARV-471, or
ARV-473. 
4
GENERAL CONSIDERATIONS
4.1
Programming Environment
All analyses will be conducted using SAS© version 9.4 or later.
4.2
General Statistical Methods
The statistical analyses will be presented for the different analysis sets as defined in Section 
3.   
4.2.1
Analysis Groups
The summary will be presented as ARV-471 200 mg, anastrozole 1 mg, and overall.
4.2.2
Descriptive Summaries
In general, numerical variables will be summarized using descriptive statistics, displaying the 
number of participants in the respective analysis group, the number of participants with data, 
mean, standard deviation, median, minimum (min) and maximum (max). 
Categorical variables will be summarized by using frequency counts and percentages. In 
addition, the number of participants with missing values will be displayed. Unless otherwise 
specified, the denominators used for calculating sample proportions will be the number of 
participants for each level of the analysis group defined above in the specified statistical 
analysis set (or a subset of the statistical analysis set under use).
Statistical methods for efficacy endpoints are described in section 10.2.
4.2.3
Presentation Conventions
Means and medians will be presented by 1 additional decimal place and standard deviation 
will be presented by 2 additional decimal places than the standard presentation level of the 
respective data. Minimum and maximum values will be presented using the same number of 
decimal places as the original data. Confidence limits will be presented by 1 additional 
decimal place than corresponding point estimates.


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Statistical Analysis Plan
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If not otherwise stated, percentages will be presented to 1 decimal place. However, when the 
percentage (or estimated proportion) is 100% exactly, no decimal place will be shown, 
whereas a presented 100.0% implies that the percentage is in the half-open interval [99.95%, 
100%). The number of decimal places may be adjusted, e.g., if the above default choices may 
lead to misinterpretation of the presented data.
If the number of participants in a category is 0, then percentage will not be displayed, and 
only a count of 0 will be shown. However, structural zeros (e.g., when the count is deemed to 
be 0 before obtaining actual data), missing data or inapplicable/unevaluable summaries will 
be presented as −, NA or NE. 
In listings, data will be sorted by study part, arm, and participant. When appropriate by visit, 
scheduled timepoint or other identifiers for sequence or type of observation.
4.3
Covariates and Strata
The stratification factors include Size of primary breast tumor (≤ 2 cm, >2 to < 5 cm, or ≥ 5 
cm) and Baseline Ki-67 local score (< 20% vs ≥ 20%). 
4.4
Subgroups
The primary endpoint will be presented for subgroups defined by the following criteria that 
will be derived from primary target lesion(s) and laboratory data instead of IRT: 
x
Size of primary breast tumor (T-stage): ≤ 2 cm, >2 to < 5 cm, or ≥ 5 cm 
x
Baseline Ki-67 score (assessed locally): < 20% vs ≥ 20% 
x
Baseline Ki-67 score (assessed centrally): < 20% vs ≥ 20% 
Other factors will be considered if the observed data imply potential findings of clinical 
interest.
4.5
Multiple Comparison/Multiplicity
This is a Phase 2 proof of concept study designed to generate data informing future studies 
about ARV-471. There are no plans for formal comparisons or hypotheses testing. There is 
no need for Type I error control. Descriptive statistics (including point estimates and two-
sided CIs) will be provided for all parameters of interest. For information purposes, all the 2-
sided CIs will be reported on both 80% and 95% confidence levels.
5
DEFINITIONS & DATA HANDLING CONVENTIONS
5.1
Study Day, Duration, and Study Periods 
5.1.1
Study Day
Day 1 will be the date corresponding to the date of first ARV-471/anastrozole dose. Study 
Day = Assessment Date – Date of Day 1 + 1 for assessment dates on or after date of Day 1. 
Study Day = Assessment Date – Date of Day 1 for assessment prior to Day 1.
Unless otherwise specified, day is the primary time unit for derived time and durations. Derived 
time units include week=7 days, month=30.436875 days, and (Gregorian) year=365.2425 
days=12 months. Thus, 1 month and 4 weeks are considered different. 


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5.1.2
Duration
Unless otherwise specified, duration of time is defined from the starting day through the ending 
day, inclusive of both boundary days.
5.2
Analysis Visit Windows
Participant visits will be presented according to the nominal visit as obtained upon the eCRF. 
All values will be included in the participant data listings.
5.3
Baseline and Change from Baseline
The baseline value is defined to be the last non-missing assessment on/before the date of the 
first ARV-471/anastrozole dose. In case the randomized subject does not receive any 
treatment, the baseline will be the last assessment on/before the date of randomization. 
Change from baseline (CFB) calculations for a treatment window assessment will be the 
applicable treatment window assessment minus the baseline assessment. If either the 
treatment window assessment value or the baseline value is/are missing, then CFB will be set 
to missing for descriptive analysis purposes, unless otherwise specified. 
5.4
Missing Data
5.4.1
Partial or Missing Dates and Time
The incomplete dates (e.g., start and/or stop dates of AE, concomitant medication) will be 
assumed as the most conservative value possible. In general, unless the available parts of the 
partial date preclude an AE to be treatment-emergent, the AE will be considered treatment-
emergent; similarly, unless the available parts of the partial date exclude a medication to be 
concomitant, the medication will be considered as a concomitant medication. 
For example, if the start date has a missing day value, the first day of the month will be 
imputed for study day computations, etc. If day is missing for an end date, the last day of the 
month will be imputed. If the start date has a missing month value, the first month of the year 
will be imputed for study day computations, etc. If month is missing for an end date, the last 
month of the year will be imputed. For determination of treatment-emergent status, the start 
date will be imputed as the date of the first dose of study drug, unless there is clear evidence 
(through comparison of partial dates/times) to suggest otherwise.
Date imputation will only be used for computational purposes such as treatment-emergent 
status, etc. Actual data values, as they appear in the original eCRFs, will be presented in the 
participant data listings. Non-monotone partial dates (e.g., day and month are non-missing 
but year is missing) need to be queried and resolved before DBL.
5.4.2
Other Missing Values
Every effort will be made to obtain the required data at each scheduled evaluation from all 
participants who have been enrolled. In general, missing data will not be imputed and the 
data will be analyzed as they are recorded.


Protocol No.:
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Version:
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Date:
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Statistical Analysis Plan
17
6
STUDY POPULATION AND DISPOSITION
6.1
Analysis Sets
The number and percentage of participants in each analysis set as defined in Section 3 will be 
summarized using the Full Analysis Set as described in Section 4.2.1.
Corresponding data listing will be provided using the Full Analysis Set.
6.2
Participant Disposition
The number and percentage of the following will be summarized using the Enrolled 
Participants /Ki-67 Evaluable Set as described in Section 4.2.1, including: 
x
Completed Treatment per Protocol
x
ARV-471/Anastrozole early discontinuation
x
Reason for ARV-471/Anastrozole early discontinuation
o
Disease Progression per Response Criteria
o
Clinical Progression
o
Withdrawal of Consent
o
Significant non-compliance
o
Pregnancy
o
Death
o
Adverse Event
o
Study Terminated by Sponsor
o
Lost to Follow-up
o
Other
x
Completed study per Protocol
x
Study early discontinuation
x
Reason for study early discontinuation
o
Withdrawal of Consent
o
Study Terminated by
o
Sponsor
o
Lost to Follow-up
o
Death
o
Other
Disposition of participants will be provided in a data listing using the Full Analysis Set.
Additionally, the number of participants with Tumor Biopsies (including Ki-67 and PgR636, 
etc.) at Screen/Cycle 1 day 15/ Cycle 6 day 18/Unscheduled will be summarized.  The 
number and percentage of participants with the tested result or uninterpretable per test per 
visit will be summarized. 
6.3
Protocol Deviations
Protocol Deviation Management version: 1.0 dated 04 Jan 2023 (by Translational Research 
In Oncology) defined the study specific procedures and responsibilities for managing 
Protocol Deviations.  Protocol Deviation severity includes minor, major or critical. The 
deviations will be categorized as:
x
Informed Consent
x
IMP/NIMP


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Statistical Analysis Plan
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x
Protocol Compliance
x
Safety
x
ICH/GCP
All protocol deviations in each arm will be summarized by severity and categories.  Protocol 
Deviation will also be listed in the Full Analysis Set.
7
DEMOGRAPHICS AND DISEASE CHARACTERISTICS
7.1
Demographics and Baseline Characteristics
The following demographic characteristics will be summarized using Full Analysis Set and 
Ki-67 Evaluable Set as described in Section 4.2.1:
x
Age (as reported in EDC) (n, mean, SD, minimum, maximum)
x
Sex (female) 
x
Age group (age ≥ 60, or age < 60)
x
Race (American Indian or Alaska Native, Asian, Black or African American, Native 
Hawaiian or other Pacific Islander, White, Other, Unknown)
x
Ethnicity (Hispanic or Latino, not Hispanic or Latino, not reported)
x
Weight (kg) at baseline (n, mean, SD, minimum, maximum)
x
Height (cm) at baseline (n, mean, SD, minimum, maximum)
x
ECOG Status (0, 1)
x
Size of primary breast tumor (T-stage) (≤ 2 cm, >2 to < 5 cm, or ≥ 5 cm)
x
Post-menopausal reason (Prior bilateral oophorectomy, Age >= 60 years, Age < 60 
and amenorrheic for at least 12 months and FSH/estradiol in the postmenopausal 
range)
Demographic characteristics will also be provided in a data listing using the Full Analysis 
Set.
7.2
Disease Staging and Disease Characteristics
The following disease staging and disease characteristics will be summarized using the Full
Analysis Set and Ki-67 Evaluable Set described in Section 4.2.1:
x
Time since initial diagnosis (months), defined as time from the date of initial diagnosis
to the date of first ARV-471/anastrozole dose (n, mean, SD, minimum, maximum)
x
Time since current staging (months), defined as time from the date of current staging
to the date of first ARV-471/anastrozole dose (n, mean, SD, minimum, maximum)
x
Primary diagnosis (ER+ HER2- Breast Cancer)
x
Stage at initial diagnosis (Stage 0, Stage IA, Stage IB, Stage IIA, Stage IIB, Stage IIIA, 
Stage IIIB, Stage IIIC, Stage IV, Unknown) 
x
Disease stage at screening (Stage 0, Stage IA, Stage IB, Stage IIA, Stage IIB, Stage 
IIIA, Stage IIIB, Stage IIIC, Stage IV, Unknown)
x
Primary tumor at initial diagnosis (TX , T0, Tis, T1mi, T1a, T1b, T1c, T2, T3, T4a, 
T4b, T4c)
x
Primary tumor at screening (TX , T0, Tis, T1mi, T1a, T1b, T1c, T2, T3, T4a, T4b, T4c)


                          Protocol No.:
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                               Version:
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                                  Date:
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Statistical Analysis Plan
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x
Imaging modality for primary tumor at screening (CT, MRI, Ultrasound, Mammogram)
x
Regional lymph node at initial diagnosis (cNX, cN0, cN1, cN2a, cN2b, cN3a, cN3b, 
cN3c)
x
Regional lymph node at screening (cNX, cN0, cN1, cN2a, cN2b, cN3a, cN3b, cN3c)
x
Distant metastasis at initial diagnosis (M0, M1, Unknown)
x
Distant metastasis at screening (M0, M1, Unknown)
x
Histopathological classification at initial diagnosis (In-Situ Carcinoma, Invasive Ductal 
Carcinoma, Invasive Lobular Carcinoma, Invasive Mixed Ductal and Lobular Breast 
Carcinoma, Invasive Carcinoma NOS, Invasive Adenocarcinoma NOS, Tubular 
Carcinoma, Invasive Mucinous Adenocarcinoma, Other)
x
Histopathological classification at screening (In-Situ Carcinoma, Invasive Ductal 
Carcinoma, Invasive Lobular Carcinoma, Invasive Mixed Ductal and Lobular Breast 
Carcinoma, Invasive Carcinoma NOS, Invasive Adenocarcinoma NOS, Tubular 
Carcinoma, Invasive Mucinous Adenocarcinoma, Other)
x
Histopathological grade at initial diagnosis (Grade 1, Grade 2, Grade 3, Grade X)
x
Histopathological grade at screening (Grade 1, Grade 2, Grade 3, Grade X)
x
Planned type of breast surgery (Breast conserving surgery, Mastectomy)
The disease staging and disease characteristics will be listed using Full Analysis Set.
7.3
Disease Staging at Post-Surgery
The number and percentage of subjects with the following disease staging at post-surgery
will be summarized using the Full Analysis Set and Ki-67 Evaluable Set described in 
Section 4.2.1:
Pathologic Tumor - ypT, n(%)
x
ypTx 
x
ypT0
x
ypTis
x
ypT1mi
x
ypT1a
x
ypT1b
x
ypT1c
x
ypT2
x
ypT3
x
ypT4a
x
ypT4b
x
ypT4c
Multiple Foci of Residual Tumor?, n(%)
x
Yes
x
No 
Pathologic Lymph Nodes - ypN, n(%)
x
ypNX 
x
ypN0
x
ypN0(i+)
x
ypN0(mol+)


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Statistical Analysis Plan
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x
ypN1
x
ypN1mi
x
ypN1a
x
ypN1b
x
ypN1c
x
ypN2
x
ypN2a
x
ypN2b
x
ypN3
x
ypN3a
x
ypN3b
x
ypN3c
Distant Metastasis (M), n(%)
x
M0
x
pM1
x
Unknown
Lymphatic Vascular Invasion Classification, n(%)
x
Present
x
Not Present
x
Unknown
The disease staging at post-surgery will be listed using Full Analysis Set.
7.4
Molecular Biology of Disease at Baseline
The molecular biology of disease - HER2 status, Ki67, Estrogen receptor, Progesterone 
receptor at baseline will be summarized using the Full Analysis Set and Ki-67 Evaluable Set:
x
Perform of HER2 status, Ki67, Estrogen receptor, Progesterone receptor (Yes, No)
x
Sample site of HER2 status, Ki67, Estrogen receptor, Progesterone receptor (Breast, 
Lymph Node, Other)
x
HER2 analytical method (IHC, ISH)
x
HER2 analytical result (0, 1+, 2+, 3+, Positive, Negative, Unknown)
x
% of Tumor cells with Ki67 (assessed locally) (n, mean, SD, minimum, maximum, < 
20% vs ≥ 20%)
x
% of Tumor cells with Ki67 (assessed centrally) (n, mean, SD, minimum, maximum, < 
20% vs ≥ 20%)
x
% of Tumor cells with Estrogen receptor (n, mean, SD, minimum, maximum, < 10% 
vs ≥ 10%)
x
% of Tumor cells with Progesterone receptor (n, mean, SD, minimum, maximum, < 1% 
vs ≥ 1%)
The molecular biology of disease will be listed using Full Analysis Set.
7.5
Prior Cancer Related Surgery/Biopsy
The following prior cancer related surgery/biopsy characteristics will be summarized 
descriptively using Full Analysis Set as described in Section 4.2.1:
x
Any prior surgery/biopsy related to the disease under trial (Yes)


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                               Version:
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                                  Date:
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Statistical Analysis Plan
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x
Procedure (Sentinel node biopsy, Axillary sampling, Fine needle aspiration, Core 
needle biopsy, Other)
x
Procedure location (Breast, Lymph node, Other) 
x
Laterality (Left, Right, Bilateral, Not applicable)
x
Time since most recent surgery/biopsy (months), defined as time from the most recent 
date of surgery to the date of first ARV-471/Anastrozole dose (n, mean, SD, 
minimum, maximum)
7.6
Medical History
Medical histories are coded according to Medical Dictionary for Regulatory Activities 
(MedDRA version 27.0 or higher) and will be classified as system organ class and preferred 
terms.
The number and percentage of participants will be summarized according to system organ class 
and preferred terms. If a participant has more than one disease within a system organ class 
and/or preferred terms the participant will be counted only once per system organ class or 
preferred terms.
The medical history will be listed using the Full Analysis Set. 
8
PROTOCOL-REQUIRED DRUG EXPOSURE AND COMPLIANCE
The dosing data for ARV-471 and Anastrozole be summarized descriptively using the Safety 
Analysis Set as described in Section 4.2.1.
The follow exposure parameters for ARV-471 and Anastrozole will be derived separately and 
will be summarized with n. mean, sd, median, min, max:
x
Duration of treatment (week) is defined as the time from the date of first dose to the
date of last dose
x
Cumulative dose (mg) is the sum of ‘Actual total daily dose’ × (End date- Start date+1) 
per record
x
Absolute Dose Intensity (mg/week) is defined as (Cumulative Dose (mg)/(Duration of 
Treatment (week). 
x
Relative Dose Intensity (%) is defined as (Absolute Dose Intensity (mg/week))/
(Initial Planned Weekly Dose (mg/week).  ARV-471 Initial Planned Weekly Dose 
(mg/week) is 1400 mg/week (200*7).  Anastrozole Initial Planned Weekly Dose 
(mg/week) is 7 mg/week (1*7).
x
Total planned dose (mg) is the sum of ‘Planned total daily dose’ × (End date- Start 
date+1) per record
x
Compliance is 100*(Cumulative dose/Total planned dose)
x
Number of compliant patients (with compliance >= 80% - <= 120%).
The number and percentage of participants with dose discontinued, dose interrupted, dose 
reduced, dose increased, reasons for the action taken (Adverse event, Participant 
missed/Skipped dose, Medication error, Other) will be presented.  All dosing data (including 


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the above derived dosing parameters) will also be presented in a data listing using the Safety 
Analysis Set.
9
PRIOR AND CONCOMITANT THERAPIES
Full Analysis Set will be used to list diagnostic and medical procedures.
9.1
Prior and Concomitant Medications
Prior and concomitant medications and on-study anti-cancer therapy will be coded according 
to WHO-Drug B3 Global version September 2024 or most current version with Anatomical 
Therapeutic Chemical (ATC) Classification System and preferred names (PN). Prior 
medications include the medications that are ended before Day 1. Concomitant medications 
include the medications that are used/started on/after Day 1 and within 30 days from the last 
administration of the study intervention (ie, study drug treatment or surgical resection, 
whichever occurs last).
The number and percentage of participants with prior medication or concomitant medications 
will be summarized by ATC level 2 category and preferred name will be summarized using 
the Full Analysis Set as described in Section 4.2.1. If a participant received more than 1 drug 
within an ATC2 or PN, the participant will be counted only once for this ATC2 and PN. 
Prior and concomitant medications and on-study anti-cancer therapy will also be provided in 
a data listing using the Full Analysis Set.
10
EFFICACY ANALYSES
10.1 Assessment
10.1.1 Tumor Biopsies
Tumor samples for Ki67, estrogen receptor (ER), and PD endpoints will be collected at 
screening, C1D15 (+ 5 days), surgical resection (after approximately 5.5 months of 
treatment). Ki-67 expression will be measured by IHC. ER expression will be measured by 
quantitative immunofluorescence. These analyses will be done in a blind manner at the 
central laboratories.
10.1.2 Radiographic Imaging
Radiographic imaging (eg, breast ultrasound, breast MRI with contrast, and/or mammogram)
will be performed at screening, C4D1 (± 7 days), and within 7 days prior to surgical 
resection. Tumor responses are assessed based on mRECIST criteria by Investigator. The 
overall tumor response per visit includes Complete Response (CR), Partial Response (PR), 
Stable Disease (SD), Progressive Disease (PD), Not Evaluable (NE).
10.1.3 Physical Exam
Caliper based measurements of the primary breast tumor will be performed during physical 
exam at screening, day 1 of cycle 1~cycle 6, and C6D18 prior to the surgery. 


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10.1.4 Local Pathological Assessments
Local pathological assessments of the tissue include surgical resection (performed after 
approximately 5.5 months of treatment) for surgical procedure (Breast Conserving Surgery
(BCS), Mastectomy), post-surgery pathologic stage (ypT and ypN stage), and post-surgery 
pathologic response (Pathological Complete Response (pCR), Pathological Partial Response 
(pPR), No Response (NR)).
10.2 Definitions of Efficacy Endpoints
10.2.1 Ki-67 Percentage at C1D15 (Primary)
The tumor biopsies Ki-67 expression (%) at baseline and C1D15 will be collected. The 
endpoint is the ratio between the Ki-67 measurements obtained from C1D15 visit and baseline, 
which will be derived as = log(Ki-67 at C1D15) - log(Ki-67 at baseline) and the treatment 
effects will be back transformed. The percentage change of Ki67 from baseline at C1D15 will 
be derived as = 100 × (% Ki67 at C1D15 - % Ki67 at baseline)/% Ki67 at baseline. 
If the value at C1D15/surgery is reported as “0”, “<1”, or other special characters will be 
imputed as ‘0.1” with % as unit.
10.2.2 ER Percentage at C1D15 
The tumor biopsies ER expression will be reported with AQUA score (absolute quantification 
score in arbitrary units) at baseline and C1D15.The endpoint is the percentage change of ER 
expression obtained from C1D15 visit and baseline, which will be derived as = 100 × (ER
AQUA score at C1D15 - ER AQUA score at baseline)/ ER AQUA score at baseline.
10.2.3 pCR Rate
Post-Surgery Pathological Response will be reported as Pathological Complete Response
(pCR), Pathological Partial Response (pPR), No Response (NR). Additionally, pCR will also 
be programmatically derived according to the definition in the protocol using Disease Staging 
– Post-Surgery data: 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 proportion of participants with pCR, which are either 
determined by site pathologist or derived based on EDC data.
10.2.4 mPEPI Score and mPEPI0 Rate
Modified Pre-operative Endocrine Prognostic Index (mPEPI) score will be derived from factors 
assigned a numerical score following Neoadjuvant endocrine treatment (NET) according to the 
following table (Ellis 2008, Sanati 2015). The factors include Ki67 expression in the surgical 
specimen, pathologic tumor size, and lymph node status. Total mPEPI score (mPEPI_T) per 
participant is the sum of mPEPI score of each factor. mPEPI0 rate is the proportion of participants 
achieving mPEPI_T 0 after treatment (before surgery). 
Pathology, biomarker status
mPEPI Score
Pathological tumor size
T1/2
0
T3/4
3
Node status


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Pathology, biomarker status
mPEPI Score
Negative
0
Positive
3
Ki67 level (centrally)
0%–2.7% 
0
>2.7%–7.3% 
1
>7.3%–19.7% 
1
>19.7%–53.1% 
2
>53.1% 
3
10.2.5 Breast Conserving Surgery (BCS) Rate
Breast conserving surgery (BCS) Rate is the proportion of participants receiving breast conserving 
surgery.
10.2.6 Radiographic Response per mRECIST in Primary Tumor during Cycle 6     
The percentage of subjects with Complete Response (CR), Partial Response (PR), Stable 
Disease (SD), Progressive Disease (PD), Not Evaluable (NE) per mRECIST at Cycle 6 (before 
surgery) will be calculated.  
Percentage change of target lesions and target lesion (primary tumor) from baseline at each 
visit and the best percentage change of target lesions and target lesion (primary tumor) from 
baseline will be summarized. 
10.2.7 Caliper-Based Response
The percentage change from the baseline of the primary breast tumor in physical exam will be 
calculated by visit. The best percentage change from baseline, Caliper-based response, which is 
maximum percentage decrease or minimum percentage increase if there is no decrease per 
participant.
10.2.8 CCCA Rate
Complete cycle cell arrest (CCCA) at Week 2/surgery is defined as Ki67 score ≤ 2.7%.  CCCA 
rate is the proportion of participants achieving CCCA at Week 2 (or C1D15)/surgery. 
10.3 Analysis of Efficacy Variables
All efficacy data and the derived endpoints will be listed. The endpoints will be analyzed
below.
10.3.1 Ki-67 Percentage at C1D15 (Primary)
Analysis of Ki-67 reduction will be based on Ki-67 Analysis Set. 
The log-transformed Ki-67 after approximately 2 weeks of treatment as a percentage of the 
baseline value, ie, the ratio between the Ki-67 measurements obtained from C1D15 visit and 
baseline, will be modelled using a GLM, with both derived stratification factors (ie, baseline 
Ki-67 score (local laboratory and central laboratory) and the tumor size) and treatment as 
covariates, or with treatment as only covariate Treatment effects for each arm will be 
summarized using the LSM and their two-sided 80% CI and 95% CI on the log scale. In 
addition, for easier interpretation of the data, the treatment effects will be back transformed 


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and expressed as the geometric means and their CIs on the original percentage scale by 
treatment arm. 
LSM difference between two arms and its two-sided 80% CI and 95% CI will be calculated on 
the log scale. The treatment effects will be back transformed and expressed as the geometric 
means and their CIs on the ratio of original percentage scale.  
The calculation will use Ki-67 score from central laboratory. 
Same analysis will be performed for the Ki-67 Percentage at surgery using Full Analysis Set.
Spider plot for individual Ki-67 value at C1D15 and Surgery, Box plot for Ki-67 percentage 
change from baseline at C1D15 and Surgery will be presented. 
10.3.2 Binary or Categorical Endpoints
Analysis of these parameters will be based on Full Analysis Set. The participants without post 
baseline assessment will be considered as Not Evaluable in Post-Surgery Pathological 
Response and Radiographic Response per mRECIST and counted in denominator.
The number and percentage of participants with Post-Surgery Pathological Response and 
Radiographic Response per mRECIST during Cycle 6 will be summarized. pCR rate, mPEPI 
rate, BCS rate, and CCCA rate will be computed by treatment arm along with the 80% CI and 
95% CI using Wilson method. 
Odds ratios of CCCA rate and mPEPI rate between the treatments adjusted for the stratification 
factors through the Cochran-Mantel-Haenszel method will be provided along with their 80% CIs 
and 95% CIs.
The number and percentage of participants with Post-Surgery Disease Staging will be summarized 
using both Full Analysis Set and Ki-67 Analysis Set.
10.3.3 Primary Tumor Assessments
Caliper-based primary breast tumor size in physical exam and its percentage change from 
baseline at each visit will be summarized with n, mean, sd, median, min, max using Full 
Analysis Set. Caliper-based response is the best percentage change from baseline (maximum 
percentage decrease or minimum percentage increase if there is no decrease per participant), 
which will be presented with n. mean, sd, median, min, max and Waterfall Plot.  
Sum of target lesion and primary target lesion at each visit will be calculated separately. The 
size and its percentage change from baseline at each visit will be summarized with n. mean, sd, 
median, min, max using Full Analysis Set. The best percentage change from baseline 
(maximum percentage decrease or minimum percentage increase if there is no decrease per 
participant) will be presented in with n. mean, sd, median, min, max and Waterfall Plot.  
A spider plot for the percentage change of target lesion from baseline will be presented.
10.3.4 ER AQUA Score Percentage at C1D15 and Surgery
ER AQUA score reduction will be analyzed using Full Analysis Set with Normalized AQUA 
score from Navigate transfer at screen and C1D15/Surgery. The percentage change of ER 
AQUA score from baseline will be analyzed using a GLM, with both derived stratification 
factors (ie, baseline Ki-67 score (from central lab only) and the tumor size) and treatment as 
covariates, or with treatment as only covariate. Treatment effects for each arm and difference 


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between two arms will be summarized using the LSM and their two-sided 80% CI and 95% 
CI.  Additionally, the percentage change of log-transformed ER AQUA score from baseline 
will be analyzed using a GLM with treatment as only covariate. Treatment effects for each arm 
and difference between two arms will be summarized using the LSM and their two-sided 80% 
CI and 95% CI.  The treatment effects will be back transformed and expressed as the geometric 
means and their CIs on the ratio of original scale. Baseline values of 0 are not imputed and the 
participants will be excluded in the summary. Post-baseline value of 0 will be imputed as 0.1
for the derivation of log transform analysis.
10.3.5 PR H-score Percentage at C1D15 and Surgery
PR (progesterone receptor) H-score (H-score = (SCORE_1)*1 + (SCORE_2)*2 + 
(SCORE_3)*3) reduction will be analyzed using Full Analysis Set with PgR636 assessment at 
screen and C1D15/Surgery. If a value includes a special character such as “<” or “>”, the value 
after the special character will be used for the derivation of H-score. Baseline values of 0 are 
not imputed and the participants will be excluded in the summary. Post-baseline value of 0 will
be imputed as 0.1 for the derivation of log transform analysis.
The percentage change of PR H-score from baseline will be analyzed using a GLM with 
treatment as only covariate. Treatment effects for each arm and difference between two arms
will be summarized using the LSM and their two-sided 80% CI and 95% CI.  Additionally, the 
percentage change of log-transformed PR H-score from baseline will be analyzed using a GLM
with treatment as only covariate. Treatment effects for each arm and difference between two 
arms will be summarized using the LSM and their two-sided 80% CI and 95% CI.  The 
treatment effects will be back transformed and expressed as the geometric means and their CIs 
on the ratio of original scale. For the log transformation, observed 0 will be converted to 0.1
for calculation.
Spider plot for individual PR H-score at C1D15 and Surgery, Box plot for PR H-score
percentage change from baseline at C1D15 and Surgery will be presented. 
10.3.6 Subgroup Analyses 
Summaries of the primary endpoint will be presented for subgroups defined by the following 
criteria: 
x
Size of primary breast tumor (T-stage): ≤ 2 cm, >2 to < 5 cm, or ≥ 5 cm 
x
Baseline Ki-67 score (assessed locally): < 20% vs ≥ 20% 
x
Baseline Ki-67 score (assessed centrally): < 20% vs ≥ 20% 
Other factors will be considered if the observed data imply potential findings of clinical 
interest. Results of the primary analysis will be reported within each subgroup. 
11 SAFETY ANALYSES
All safety analyses will be performed on the Safety Analysis Set.


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11.1 Adverse Events
Adverse events (AE) will be coded using MedDRA 27.0 or higher and graded according to 
the NCI-CTCAE 5.0.
Summaries of AEs will be based on treatment-emergent AEs (TEAEs). A TEAE is an AE 
that emerges or worsens (ie increase in CTCAE grade) on/after the first dose of ARV-
471/Anastrozole to 30 days from the last administration of the study intervention (ie, study 
drug treatment or surgical resection, whichever occurs last). TEAE summaries will be 
presented by System Organ Class (SOC) and Preferred Term (PT). Although AEs may be 
reported more than once for a PT or SOC in a participant, each participant will only be 
counted once per SOC and PT.
An overview of Treatment Emergent Adverse Events (TEAEs), including number and 
percent of participants who had any TEAE, TEAE related to study drug, serious TEAEs, 
serious TEAEs related to study drug, TEAE leading to drug withdrawn, TEAEs leading to 
drug interrupted, TEAEs leading to dose reduced, TEAE related to study drug leading to drug 
withdrawn, TEAEs related to study drug leading to drug interrupted, TEAEs related to study 
drug leading to dose reduced, TEAEs ≥grade 3 in severity, TEAEs related to study drug ≥
grade 3 in severity, TEAE leading to death.
Number and percentages of participants with TEAEs will be presented by SOC and PT in the 
following summaries:
x
TEAEs 
x
TEAEs related to study drug
x
TEAEs with grade 3 or higher
x
TEAEs with grade 3 or higher related to study drug
x
Serious TEAEs 
x
Serious TEAEs to study drug
x
TEAEs leading to drug withdrawn
x
TEAEs related to study drug leading to drug withdrawn
x
TEAEs leading to drug interrupted
x
TEAEs related to study drug leading to drug interrupted
x
TEAEs leading to dose reduced
x
TEAEs related to study drug leading to dose reduced
x
TEAEs leading to death
Number and percentages of participants with TEAEs will be presented by PT in the following 
summaries:
x
TEAEs 
x
TEAEs related to study drug
x
Serious TEAEs 
x
Serious TEAEs to study drug
Tornado plots for treatment emergent adverse events in >= 5% subjects of any arm by 
Preferred Term and with Grade 3 or higher by Preferred Term will be presented.


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Number and percentages of participants with TEAEs will be presented by SOC, PT and 
maximum CTCAE grade in the following summaries:
x
TEAEs 
x
TEAEs related to study drug
x
Serious TEAEs 
x
Serious TEAEs to study drug
Number and percentages of participants with MedDRA SMQ for Torsade de Pointes will be 
presented by PT and maximum CTCAE grade. PTs include Electrocardiogram QT interval 
abnormal, Electrocardiogram QT prolonged, Long QT syndrome, Long QT syndrome 
congenital, Torsade de pointes, Ventricular tachycardia, Arrhythmic storm, Cardiac arrest, 
Cardiac death, Cardiac fibrillation, Cardio-respiratory arrest, Electrocardiogram 
repolarization abnormality, Electrocardiogram U wave inversion, Electrocardiogram U wave 
present, Electrocardiogram U-wave abnormality, Loss of consciousness, Seizure, Sudden 
cardiac death, Sudden death, Syncope, Ventricular arrhythmia, Ventricular fibrillation, 
Ventricular flutter, Ventricular tachyarrhythmia.
Participant listings will be provided for participants with all AEs.
11.2 Deaths
The reason of subject death will be summarized using Safety Analysis Set. Death information 
will be provided in a listing.
11.3 Vital Signs
Vital signs parameters with abnormal clinically significant will be provided in a data listing.
11.4 Clinical Laboratory 
For lab values in the form of <x, ≤x, below lower quantification limit, etc., the value will be 
imputed as x/2 or half of the lower quantification limit for the purpose of numerical descriptive 
summary. For lab values in the form of >x, ≥x, above upper quantification limit, etc., the value 
will be imputed as x or upper quantification limit for the purpose of numerical descriptive 
summary. When such imputation occurs, footnotes will be presented to clarify the imputation 
rule. The original lab values will be presented in data listings.
The Laboratory test value and change from baseline for continuous parameters over 
hematology tests, chemistry tests, coagulation tests will be summarized using descriptive 
statistics (n, mean, SD, median, minimum, maximum) by visit.
The value of hematology tests, coagulation tests, and chemistry tests will be graded with 
CTCAE 5.0. Shift of hematology tests, coagulation tests, and chemistry tests from baseline 
CTCAE grade to the worst postbaseline CTCAE grade will be presented. If a parameter 
includes both hypo- and hyper- CTCAE grade derivation, hypo- and hyper- will be tabulated 
separately. If the baseline is not CTCAE gradable (e.g., AST increase), the baseline 
measurement will be categorized as low/normal/high according to reference ranges.
Laboratory hematology, chemistry, coagulation, and urinalysis will be provided in data listings. 


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11.5 12-Lead Electrocardiogram
Triplicate 12-lead ECGs include Heart Rate, PR Interval, QRS Duration, QT Interval, QTcB 
Interval (Bazette's), QTcF Interval (Fridericia's). The mean of each parameter per visit will be 
used to summary. The value and change from baseline at each visit/timepoint will be 
summarized using descriptive statistics (n, mean, standard deviation, median, minimum, and 
maximum). If a parameter is tested only one time, the value will be used for summary directly. 
The number and percentage of participants in the following QTcB and QTcF categories will 
also be summarized:
x
QTcB/QTcF at Baseline
o
QTcB/QTcF >450 msec  
o
QTcB/QTcF >480 msec  
o
QTcB/QTcF >500 msec  
x
QTcB/QTcF Worst Post-Baseline
o
QTcB/QTcF >450 msec  
o
QTcB/QTcF >480 msec  
o
QTcB/QTcF >500 msec  
x
QTcB/QTcF Worst Change from Baseline
o
>30 msec       
o
>60 msec       
All ECG data (scheduled or unscheduled) will be displayed in a data listing.
11.6 Eastern Cooperative Oncology Group (ECOG) Performance Status
All ECOG scores will be provided in a data listing.
12 OTHER ANALYSES
12.1 Pharmacokinetics
Pharmacokinetic blood samples from participants receiving ARV-471 may be collected at 
pre-dose, 1 hour (± 15 min) post-dose, 2 hours (± 15 min) post-dose, 4 hours (± 30 min) post-
dose on Cycle 2 Day 1, pre-biopsy on Cycle 1 Day 15, and pre-surgery on Cycle 6 Day 18. 
The plasma concentrations of ARV-471 and ARV-473 of individual participants will be 
presented by listings and summarized. 
The plasma concentrations of ARV-471 and ARV-473 on Cycle 2 Day 1 will be summarized 
by time-point using PK analysis set. The following concentration data on Cycle 2 Day 1 
should be flagged and excluded from summary. 
a.
Pre-dose samples are collected after dosing time. 
b. Post-dose samples are collected out of time window. 
c.
Received ARV-471 dose is different from the planned dose
Correlation of population PK model-derived PK parameters (AUC, Cmin, Cmax) with ER 
reduction or other response parameters may be explored. The analysis plan and report may be 
provided separately. 


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12.2 Pharmacodynamics
Exploratory analyses include evaluation of the effects of ARV-471 and anastrozole, 
respectively, on Ki-67, and ER degradation by ARV-471 in tumors at the time of surgical 
resection. Changes in ER and Ki-67 expression between baseline and Cycle 6 surgical tumor 
samples as well as rates of CCCA in the cycle 6 surgical samples will be summarized for the 
full analysis set. The ER changes will be reported as a percentage change from baseline and 
derived as: 100 x (ER AQUA at surgery – ER AQUA at baseline)/ER AQUA at baseline. The 
Ki67 changes will be reported as a percentage change from baseline and derived as: 100 x (% 
Ki67 at surgery - % Ki67 at baseline)/% Ki67 at baseline. Treatment effects for each arm will 
be summarized using the LSM and their two-sided 80% CI and 95% CI.
Complete cycle cell arrest (CCCA) at surgical resection is defined as Ki67 score ≤ 2.7%.  CCCA 
rate is the proportion of participants achieving CCCA at surgical resection.
Any additional explorative pharmacodynamics analysis if needed will be described in a 
separate plan.
13 SCHEDULE OF ANALYSES
The final analysis will take place when all participants discontinue the study.
14 REFERENCES
1. Ellis MJ, etc. Outcome Prediction for Estrogen Receptor–Positive Breast Cancer Based 
on Postneoadjuvant Endocrine Therapy Tumor Characteristics. J Natl Cancer Inst. 2008 
Oct 1; 100(19): 1380–1388.
2. Hurvitz SA, Quiroga V, Park YH, et al. Neoadjuvant giredestrant (GDC-9545) + 
palbociclib versus anastrozole + palbociclib in postmenopausal women with estrogen 
receptor-positive, HER2-negative, untreated early breast cancer: Primary analysis of the 
randomized, open-label, phase II coopERA breast cancer study. San Antonio Breast 
Cancer Symposium 2021. Cancer Res 15 February 2022; 82 (4_Supplement): PD13–06.
3. ICH Harmonised Tripartite Guideline E9, Statistical Principles for Clinical Trials, 1998
4. ICH Harmonised Tripartite Guideline E3, Structure and Content of Clinical Study 
Reports. 1995
5. ICH Harmonised Tripartite Guideline E6(R1), Guideline for Good Clinical Practice, 1996
6. ICH guideline E2F, Note for guidance on development safety update reports, 
EMA/CHMP/ICH/309348/2008, September 2010
7. ICH E9 (R1) addendum on estimands and sensitivity analysis in clinical trials to the 
guideline on statistical 6 principles for clinical trials, Step 2b (Draft), 
EMA/CHMP/ICH/436221/2017, 2017
8. Sanati S. etc. Abstract P4-11-13: Validation of the preoperative endocrine prognostic 
index in the ACOSOG (Alliance) Z1031 neoadjuvant aromatase inhibitor trial. Cancer 
Research, POSTER SESSION ABSTRACTS, MAY 01, 2015.


Protocol No.: ARV-471-BC-201
Version:v2
Version Date: 15Nov2024
TLF Shells
1
Protocol No: ARV-471-BC-201
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
Table and Figure Shells
Author: 
SAP Version: v3.0
Table and Listing Shell Version: v2.0




 
 
 
3 
INTRODUCTION 
The following are mock table and listing shells. These represent the format of the analysis tables 
that will be programmed for this project. These are based on the statistical analysis plan (SAP) 
for study ARV-471-BC-201. 
Statistical results are represented with placeholders such as “xxx.x.” These placeholders will be 
populated with results when the tables are programmed based on the data. 
These shells are in Microsoft Word, whereas the programmed tables are developed with SAS. 
Very minor differences in appearance should be expected between these shells and the 
programmed tables, although the general layout and format of the programmed tables will be 
consistent with these shells. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


4
TABLE OF CONTENTS 
REVISIONS .............................................................................................................................................................................................. 12 
GLOBAL CONVENTIONS ..................................................................................................................................................................... 13 
Table 14.1.1.1 Summary of Analysis Sets  Analysis Set: Full Analysis Set ........................................................................................ 16 
Table 14.1.1.2 Summary of Participants with Tumor Biospsy  Analysis Set: Full Analysis Set ......................................................... 17 
Table 14.1.2.1 Summary of Disposition and Discontinuation  Analysis Set: Enrolled Participants .................................................... 18 
Table 14.1.2.2 Summary of Disposition and Discontinuation  Analysis Set: Ki-67 Evaluable Set ..................................................... 19 
Table 14.1.3 Summary of Protocol Deviation  Analysis Set: Full Analysis Set .................................................................................. 20 
Table 14.1.4.1 Summary of Demographic Characteristics  Analysis Set: Full Analysis Set ............................................................... 21 
Table 14.1.4.2 Summary of Demographic Characteristics  Analysis Set: Ki-67 Evaluable Set .......................................................... 22 
Table 14.1.5 Summary of Medical History by System Organ Class and Preferred Term Analysis Set: Full Analysis Set ................. 23 
Table 14.1.6.1 Summary of Disease Staging and Disease Characteristics  Analysis Set: Full Analysis Set ....................................... 24 
Table 14.1.6.2 Summary of Disease Staging and Disease Characteristics Analysis Set: Ki-67 Evaluable Set ................................... 27 
Table 14.1.7.1 Summary of Disease Molecular Biology at Baseline  Analysis Set: Full Analysis Set ............................................... 28 
Table 14.1.7.2 Summary of Disease Molecular Biology at Baseline Analysis Set: Ki-67 Evaluable Set ........................................... 30 
Table 14.1.8 Summary of Prior Cancer Related Surgery/Biopsy  Analysis Set: Full Analysis Set ..................................................... 31 
Table 14.1.9 Summary of Prior Medication Analysis Set: Full Analysis Set....................................................................................... 32 
Table 14.1.10 Summary of Concomitant Medication Analysis Set: Full Analysis Set ........................................................................ 33 
Table 14.1.11 Summary of ARV-471 and Anastrozole Compliance and Exposure  Analysis Set: Safety Analysis Set ..................... 34 
Table 14.2.1.1.1 Summary of Ki-67 Percentage Change from Baseline at C1D15 with Central Ki-67 as a Covariate  Analysis Set: 
Ki-67 Evaluable Set .............................................................................................................................................................................. 36 
Table 14.2.1.1.2 Summary of Ki-67 Percentage Change from Baseline at C1D15 with Local Ki-67 as a Covariate Analysis Set: Ki-
67 Evaluable Set ................................................................................................................................................................................... 37 
Table 14.2.1.1.3 Summary of Ki-67 Percentage Change from Baseline at C1D15 without Covariate   Analysis Set: Ki-67 Evaluable 
Set ......................................................................................................................................................................................................... 38 


 
 
 
5 
Table 14.2.1.2.1 Summary of Ki-67 Percentage Change from Baseline at C1D15– Subgroup Analysis by Tumor Size   Analysis Set: 
Ki-67 Evaluable Set .............................................................................................................................................................................. 39 
Table 14.2.1.2.2  Summary of Ki-67 Percentage Change from Baseline at C1D15 – Subgroup Analysis by Local Ki-67 Baseline 
Score  Analysis Set: Ki-67 Evaluable Set ............................................................................................................................................. 41 
Table 14.2.1.2.3 Summary of Ki-67 Percentage Change from Baseline at C1D15– Subgroup Analysis by Central Ki-67 Baseline 
Score of 20%  Analysis Set: Ki-67 Evaluable Set ................................................................................................................................ 42 
Table 14.2.1.2.4 Summary of Ki-67 Percentage Change from Baseline at C1D15 – Subgroup Analysis by Central Ki-67 Baseline 
Score of 5%  Analysis Set: Ki-67 Evaluable Set .................................................................................................................................. 44 
Table 14.2.1.3.1 Summary of Ki-67 Percentage Change from Baseline at Surgery with Central Ki-67 as a Covariate  Analysis Set: 
Full Analysis Set ................................................................................................................................................................................... 46 
Table 14.2.1.3.2 Summary of Ki-67 Percentage Change from Baseline at Surgery with Local Ki-67 as a Covariate Analysis Set: 
Full Analysis Set ................................................................................................................................................................................... 47 
Table 14.2.1.3.3 Summary of Ki-67 Percentage Change from Baseline at Surgery without Covariate Analysis Set: Full Analysis Set
............................................................................................................................................................................................................... 48 
Table 14.2.1.4.1 Summary of Ki-67 Percentage Change from Baseline at Surgery – Subgroup Analysis by Tumor Size   Analysis 
Set: Full Analysis Set ............................................................................................................................................................................ 49 
Table 14.2.1.4.2 Summary of Ki-67 Percentage Change from Baseline at Surgery – Subgroup Analysis by Local Ki-67 Baseline 
Score  Analysis Set: Full Analysis Set .................................................................................................................................................. 51 
Table 14.2.1.4.3 Summary of Ki-67 Percentage Change from Baseline at Surgery – Subgroup Analysis by Central Ki-67 Baseline 
Score  Analysis Set: Full Analysis Set .................................................................................................................................................. 53 
Table 14.2.1.5.1 Summary of Concordance Ki-67 Baseline Score between Central and Local Laboratories Analysis Set: Ki-67 
Evaluable Set ........................................................................................................................................................................................ 55 
Table 14.2.1.5.2 Summary of Concordance Central/Local Ki-67 Baseline Score with Randomization Baseline Ki-67 Score Analysis 
Set: Ki-67 Evaluable Set ....................................................................................................................................................................... 56 
Table 14.2.1.5.3 Summary of Concordance Acutal Primary Breast Tumor Size with Randomization Primary Breast Tumor Size 
Analysis Set: Ki-67 Evaluable Set ........................................................................................................................................................ 57 
Table 14.2.2.1.1 Summary of Post-Surgery Pathological Response and pCR Rate - Determined by Site Pathologist Analysis Set: 
Full Analysis Set ................................................................................................................................................................................... 58 


 
 
 
6 
Table 14.2.2.1.2 Summary of Post-Surgery Pathological Response and pCR Rate – Calculated  Analysis Set: Full Analysis Set .... 59 
Table 14.2.2.1.3.1 Summary of Post-Surgery Disease Staging Analysis Set: Full Analysis Set ......................................................... 60 
Table 14.2.2.1.3.2 Summary of Post-Surgery Disease Staging Analysis Set: Ki-67 Evaluable Set .................................................... 61 
Table 14.2.2.2 Summary of Modified Pre-operative Endocrine Prognostic Index (mPEPI) Score and mPEPI 0 Rate  Analysis Set: 
Full Analysis Set ................................................................................................................................................................................... 62 
Table 14.2.2.3 Summary of Breast Conserving Surgery (BCS) and BCS Rate  Analysis Set: Full Analysis Set ............................... 63 
Table 14.2.2.4 Summary of Radiographic Response per mRECIST during Cycle 6 Analysis Set: Full Analysis Set ........................ 64 
Table 14.2.2.5.1 Summary of Complete Cycle Cell Arrest (CCCA) and CCCA Rate  Analysis Set: Full Analysis Set ..................... 65 
Table 14.2.2.5.2 Summary of Complete Cycle Cell Arrest (CCCA) and CCCA Rate – Subgroup Analysis by Central Ki-67 Baseline 
Score Analysis Set: Full Analysis Set ................................................................................................................................................... 67 
Table 14.2.3.1.1 Summary of the Primary Breast Tumor Change - Caliper-based Analysis Set: Full Analysis Set ........................... 69 
Table 14.2.3.1.2 Summary of the Primary Breast Tumor Change - Caliper-based by Baseline Tumor Size Analysis Set: Full 
Analysis Set .......................................................................................................................................................................................... 70 
Table 14.2.3.2.1 Summary of Target Lesion Change Analysis Set: Full Analysis Set ........................................................................ 71 
Table 14.2.3.2.2 Summary of Target Lesion Change by Baseline Tumor Size Analysis Set: Full Analysis Set ................................. 72 
Table 14.2.3.3.1 Summary of Target Lesion (Primary Tumor) Change Analysis Set: Full Analysis Set ............................................ 73 
Table 14.2.3.3.2 Summary of Target Lesion (Primary Tumor) Change by Baseline Tumor SizeAnalysis Set: Full Analysis Set ..... 74 
Table 14.2.4.1.1 Summary of ER AQUA Score Percentage Change at C1D15 from Baseline Value Analysis Set: Full Analysis Set
............................................................................................................................................................................................................... 75 
Table 14.2.4.1.2 Summary of ER AQUA Score Percentage Change at C1D15 from Baseline Value without Covariate   Analysis 
Set: Full Analysis Set ............................................................................................................................................................................ 76 
Table 14.2.4.1.3 Summary of Log-Transformed ER AQUA Score Change at C1D15 from Baseline Value without Covariate   
Analysis Set: Full Analysis Set ............................................................................................................................................................. 77 
Table 14.2.4.2.1 Summary of ER AQUA Score Percentage Change at Surgery from Baseline Value Analysis Set: Full Analysis Set
............................................................................................................................................................................................................... 78 
Table 14.2.4.2.2 Summary of ER AQUA Score Percentage Change at Surgery from Baseline Value without Covariate   Analysis 
Set: Full Analysis Set ............................................................................................................................................................................ 79 


 
 
 
7 
Table 14.2.4.2.3 Summary of Log-Transformed ER AQUA Score Change at Surgery from Baseline Value without Covariate   
Analysis Set: Full Analysis Set ............................................................................................................................................................. 80 
Table 14.2.5.1.1 Summary of PR H-score Percentage Change at C1D15 from Baseline Value without Covariate   Analysis Set: Full 
Analysis Set .......................................................................................................................................................................................... 81 
Table 14.2.5.1.2 Summary of Log-Transformed PR H-score Change at C1D15 from Baseline Value without Covariate   Analysis 
Set: Full Analysis Set ............................................................................................................................................................................ 82 
Table 14.2.5.2.1 Summary of PR H-score Percentage Change at Surgery from Baseline Value without Covariate   Analysis Set: Full 
Analysis Set .......................................................................................................................................................................................... 83 
Table 14.2.5.2.2 Summary of Log-Transformed PR H-score Change at Surgery from Baseline Value without Covariate   Analysis 
Set: Full Analysis Set ............................................................................................................................................................................ 84 
Table 14.3.1 Summary of Treatment Emergent Adverse Events Overview   Analysis Set: Safety Analysis Set ................................ 85 
Table 14.3.2.1 Summary of Treatment Emergent Adverse Events by System Organ Class and Preferred Term     Analysis Set: 
Safety Analysis Set ............................................................................................................................................................................... 86 
Table 14.3.2.2 Summary of Treatment Emergent Adverse Events Related to Study Drug by System Organ Class  and Preferred 
Term  Analysis Set: Safety Analysis Set .............................................................................................................................................. 87 
Table 14.3.2.3 Summary of Treatment Emergent Adverse Events with Grade 3 or Higher by System Organ Class  and Preferred 
Term  Analysis Set: Safety Analysis Set .............................................................................................................................................. 87 
Table 14.3.2.4 Summary of Treatment Emergent Adverse Events with Grade 3 or Higher Related to Study Drug by System Organ 
Class  and Preferred Term  Analysis Set: Safety Analysis Set ............................................................................................................. 87 
Table 14.3.2.5.1 Summary of Treatment Emergent Adverse Events Leading to Drug Withdrawn by System Organ Class  and 
Preferred Term  Analysis Set: Safety Analysis Set .............................................................................................................................. 87 
Table 14.3.2.5.2 Summary of Treatment Emergent Adverse Events Related to Study Drug Leading to Drug Withdrawn  by System 
Organ Class and Preferred Term  Analysis Set: Safety Analysis Set ................................................................................................... 88 
Table 14.3.2.6.1 Summary of Treatment Emergent Adverse Events Leading to Drug Interrupted by System Organ Class  and 
Preferred Term  Analysis Set: Safety Analysis Set .............................................................................................................................. 88 
Table 14.3.2.6.2 Summary of Treatment Emergent Adverse Events Related to Study Drug Leading to Drug Interrupted  by System 
Organ Class and Preferred Term  Analysis Set: Safety Analysis Set ................................................................................................... 88 


 
 
 
8 
Table 14.3.2.7.1 Summary of Treatment Emergent Adverse Events Leading to Dose Reduced by System Organ Class  and Preferred 
Term  Analysis Set: Safety Analysis Set .............................................................................................................................................. 88 
Table 14.3.2.7.2 Summary of Treatment Emergent Adverse Events Related to Study Drug Leading to Dose Reduced  by System 
Organ Class and Preferred Term  Analysis Set: Safety Analysis Set ................................................................................................... 88 
Table 14.3.2.8 Summary of Treatment Emergent Adverse Events by Preferred Term  Analysis Set: Safety Analysis Set ................ 89 
Table 14.3.2.9 Summary of Treatment Emergent Adverse Events Related to Study Drug by Preferred Term  Analysis Set: Safety 
Analysis Set .......................................................................................................................................................................................... 89 
Table 14.3.2.10  Summary of Treatment Emergent Adverse Events by System Organ Class,  Preferred Term and Maximum CTCAE 
Grade  Analysis Set: Safety Analysis Set ............................................................................................................................................. 90 
Table 14.3.2.11 Summary of Treatment Emergent Adverse Events Related to Study Drug by System Organ Class,  Preferred Term 
and Maximum CTCAE Grade  Analysis Set: Safety Analysis Set ....................................................................................................... 90 
Table 14.3.2.12 Summary of MedDRA SMQ for Torsade de Pointes by Preferred Term and Maximum CTCAE Grade  Analysis 
Set: Safety Analysis Set ........................................................................................................................................................................ 91 
Table 14.3.3.1 Summary of Serious Treatment Emergent Adverse Events by System Organ Class   and Preferred Term  Analysis 
Set: Safety Analysis Set ........................................................................................................................................................................ 92 
Table 14.3.3.2 Summary of Serious Treatment Emergent Adverse Events Related to Study Drug by System Organ Class  and 
Preferred Term  Analysis Set: Safety Analysis Set .............................................................................................................................. 92 
Table 14.3.3.3 Summary of Serious Treatment Emergent Adverse Events by Preferred Term  Analysis Set: Safety Analysis Set ... 92 
Table 14.3.3.4 Summary of Serious Treatment Emergent Adverse Events Related to Study Drug by Preferred Term  Analysis Set: 
Safety Analysis Set ............................................................................................................................................................................... 93 
Table 14.3.3.5 Summary of Serious Treatment Emergent Adverse Events by System Organ Class,  Preferred Term and Maximum 
CTCAE Grade Analysis Set: Safety Analysis Set ................................................................................................................................ 93 
Table 14.3.3.6 Summary of Serious Treatment Emergent Adverse Events Related to Study Drug by System Organ Class,  Preferred 
Term and Maximum CTCAE Grade  Analysis Set: Safety Analysis Set ............................................................................................. 93 
Table 14.3.3.7 Summary of Treatment Emergent Adverse Events Leading to Death by System Organ Class  and Preferred Term  
Analysis Set: Safety Analysis Set ......................................................................................................................................................... 93 
Table 14.3.3.8  Summary of Subject Death  Analysis Set: Safety Analysis Set .................................................................................. 95 
Table 14.3.7.1 Summary of Hematology Laboratory by Visit  Analysis Set: Safety Analysis Set ...................................................... 96 


 
 
 
9 
Table 14.3.7.3 Summary of Coagulation Laboratory by Visit  Analysis Set: Safety Analysis Set ...................................................... 97 
Table 14.3.7.5 Summary of Serum Chemistry Laboratory by Visit  Analysis Set: Safety Analysis Set ............................................. 97 
Table 14.3.7.2.1 Shift of Hematology CTCAE Grade from Baseline to Worst Post-baseline  Analysis Set: Safety Analysis Set ..... 98 
Table 14.3.7.2.2 Summary of Hematology CTCAE On-Treatment Worsening Analysis Set: Safety Analysis Set ............................ 99 
Table 14.3.7.4 Shift of Coagulation CTCAE Grade from Baseline to Worst Post-baseline  Analysis Set: Safety Analysis Set ....... 100 
Table 14.3.7.6 Shift of Serum Chemistry CTCAE Grade from Baseline to Worst Post-baseline  Analysis Set: Safety Analysis Set
............................................................................................................................................................................................................. 100 
Table 14.3.8.1 Summary of 12-lead ECGs by Visit  Analysis Set: Safety Analysis Set .................................................................... 101 
Table 14.3.8.2 Summary of QTcF/QTcB Interval Clinically Significant  Analysis Set: Safety Analysis Set ................................... 102 
Table 14.3.10 Summary of ARV-471 and ARV-473 Plasma Concentration (unit) by Visit  Analysis Set: Pharmacokinetic Analysis 
Set ....................................................................................................................................................................................................... 103 
Figure 14.2.1.1 Spider Plot for Individual Ki-67 Value   Analysis Set: Full Analysis Set ................................................................ 104 
Figure 14.2.1.2.1 Box Plot for Ki-67 Percentage Change from Baseline at Cycle 1 Day 15   Analysis Set: Ki-67 Evaluable Set ... 105 
Figure 14.2.1.2.2 Box Plot for Ki-67 Percentage Change from Baseline at Surgery  Analysis Set: Full Analysis Set ..................... 106 
Figure 14.2.3.1 Waterfall Plot for Best Percentage Change of Primary Tumor from Baseline (Caliper-based)  Analysis Set: Full 
Analysis Set ........................................................................................................................................................................................ 107 
Figure 14.2.3.2.1 Waterfall Plot for Best Percentage Change of Target Lesion from Baseline  Analysis Set: Full Analysis Set ..... 108 
Figure 14.2.3.2.2 Spider Plot for the Percent Target Lesion Size Change from Baseline by Subject and Timepoint Analysis Set: Full 
Analysis Set ........................................................................................................................................................................................ 109 
Figure 14.2.4.1 Spider Plot for Individual ER AQUA Score  Analysis Set: Full Analysis Set ......................................................... 110 
Figure 14.2.4.2.1 Box Plot for ER AQUA Score Percentage Change from Baseline at Cycle 1 Day 15  Analysis Set: Full Analysis 
Set ....................................................................................................................................................................................................... 111 
Figure 14.2.4.2.2 Box Plot for ER AQUA Score Percentage Change from Baseline at Surgery  Analysis Set: Full Analysis Set ... 112 
Figure 14.2.5.1 Spider Plot for Individual PR H-score  Analysis Set: Full Analysis Set ................................................................... 113 
Figure 14.2.5.2.1 Box Plot for PR H-score Percentage Change from Baseline at Cycle 1 Day 15     Analysis Set: Full Analysis Set
............................................................................................................................................................................................................. 114 


 
 
 
10 
Figure 14.2.5.2.2 Box Plot for PR H-score Percentage Change from Baseline at Surgery     Analysis Set: Full Analysis Set ......... 115 
Figure 14.3.2.8  Tornado Plot for Treatment Emergent Adverse Events by Preferred Term  Analysis Set: Safety Analysis Set ..... 116 
Listing 16.2.1.1 Subject Enrollment  Analysis Set: Full Analysis Set ............................................................................................... 117 
Listing 16.2.1.2 Subject Disposition  Analysis Set: Enrolled Participants ......................................................................................... 118 
Listing 16.2.2 Deviations from the Clinical Protocol Analysis Set: Full Analysis Set ...................................................................... 119 
Listing 16.2.4.1 Demographic Characteristics  Analysis Set: Full Analysis Set ................................................................................ 120 
Listing 16.2.4.2 Medical History Analysis Set: Full Analysis Set ..................................................................................................... 121 
Listing 16.2.4.3 Disease Staging - Initial Diagnosis  Analysis Set: Full Analysis Set ....................................................................... 122 
Listing 16.2.4.4 Disease Staging - Current Diagnosis  Analysis Set: Full Analysis Set .................................................................... 123 
Listing 16.2.4.5 Molecular Biology of Disease   Analysis Set: Full Analysis Set ............................................................................. 124 
Listing 16.2.4.6 Prior and Concomitant Medications  Analysis Set: Full Analysis Set ..................................................................... 125 
Listing 16.2.5.1 Study Drug Exposure and Compliance  Analysis Set: Safety Analysis Set ............................................................. 126 
Listing 16.2.5.2 Study Drug Administration  Analysis Set: Safety Analysis Set ............................................................................... 127 
Listing 16.2.5.3 PK Dosing - ARV-471  Analysis Set: Safety Analysis Set ...................................................................................... 128 
Listing 16.2.5.4 ARV-471 and ARV-473 Plasma Concentration Analysis Set: PK Analysis Set ..................................................... 129 
Listing 16.2.6.1 Efficacy Parameters – Part 1 of 2  Analysis Set: Full Analysis Set ......................................................................... 130 
Listing 16.2.6.2 Efficacy Parameters – Part 2 of 2 Analysis Set: Full Analysis Set .......................................................................... 131 
Listing 16.2.6.3 Target Lesion (TL)  Analysis Set: Full Analysis Set ................................................................................................ 132 
Listing 16.2.6.4 Primary Breast Tumor Change - Caliper-based  Analysis Set: Full Analysis Set .................................................... 133 
Listing 16.2.6.5 Tumor Biopsy  Analysis Set: Full Analysis Set ....................................................................................................... 134 
Listing 16.2.6.6 Imaging Response Assessment - mRECIST  Analysis Set: Full Analysis Set ......................................................... 135 
Listing 16.2.6.7 Cytology Results  Analysis Set: Full Analysis Set ................................................................................................... 136 
Listing 16.2.6.8 Disease Staging - Post-Surgery  Analysis Set: Full Analysis Set ............................................................................. 137 
Listing 16.2.7.1 Adverse Events by Subject  Analysis Set: Safety Analysis Set ............................................................................... 138 
Listing 16.2.7.2 Serious Adverse Events by Subject  Analysis Set: Safety Analysis Set .................................................................. 138 


 
 
 
11 
Listing 16.2.8.1 Hematology Tests with CTCAE Grade ≥ 3 Analysis Set: Safety Analysis Set ....................................................... 140 
Listing 16.2.8.2 Clinical Chemistry Tests with CTCAE Grade ≥ 3  Analysis Set: Safety Analysis Set ............................................ 140 
Listing 16.2.8.3 Hematology Tests  Analysis Set: Safety Analysis Set ............................................................................................. 141 
Listing 16.2.8.4 Clinical Chemistry Tests  Analysis Set: Safety Analysis Set ................................................................................... 141 
Listing 16.2.8.5 Coagulation Tests   Analysis Set: Safety Analysis Set ............................................................................................. 141 
Listing 16.2.8.6 Urinalysis  Analysis Set: Safety Analysis Set .......................................................................................................... 142 
Listing 16.2.9 Vital Signs Analysis Set: Safety Analysis Set ............................................................................................................. 143 
Listing 16.2.10 12-Lead ECG  Analysis Set: Safety Analysis Set ..................................................................................................... 144 
Listing 16.2.11 ECOG Performance Status   Analysis Set: Safety Analysis Set................................................................................ 145 
 
 


 
 
 
12 
REVISIONS 
Date 
Brief Description 
10March2023 
First draft 0.1 
17April2023 
Updates based on Arvinas comments 
24April2023 
Accept updates in Version 0.2 and correct some typo 
15Jan2024 
Add more TFL shells based on Arvinas comments on dryrun TFLs 
24May2024 
Add additional TFL shells based on Arvinas comments and new requests 
03June2024 
Accept the updates in version 0.4 
24June2024 
Update Baseline definition 
02October2024 
Update based on Arvinas’ comments on dryrun #2 draft  
11October2024 
Update based on Arvinas’ replies on the Caidya’s updates and meeting discussion on 08OCT2024: 
* Update the definition of subgroups – derivation will be based on EDC and lab data instead of IRT 
* Add summary for participants with Tumor Biopsies at each visit, medical history, absolute dose intensity, 
relative dose intensity, subgroup analysis for change of tumor size by baseline tumor size category  
* Add additional plots for KI-67 at surgery, ER AQUA Score, PR H-score 
* Update Concomitant Medications and TEAE definition 
14November2024 
* Accept changes in version 1.2 
* Update based on Arvinas’ comments on dryrun #2 Final: add Grade 3 or higher panel in Figure 14.3.2.8; 
update footnotes or contents text for more details; Renumbering the listings 
15November2024 
Accept Changes in version 1.2 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


 
 
 
13 
GLOBAL CONVENTIONS 
Format and Ordering of Groups 
Columns in summary tables will be ordered as follow: 
ARV-471 200 mg  
N=XX 
n (%) 
Anastrozole 1 mg  
N=XX 
n (%) 
Total 
N=XXX 
n (%) 
 “Total” column in some efficacy tables will be removed if it is not necessary. 
General Display Conventions 
Summary tables and subject data listings will be in landscape format. Table titles will be centered. 
Sorting Conventions 
For MH summaries, Primary System Organ Classes (SOCs) will be ordered descending count for All Subjects and Preferred Terms 
(PTs) will be ordered by descending count for All Subjects or alphabetically for PTs with the same count for All Subjects. 
For AE summaries, Primary SOCs will be ordered descending count for All Subjects and PTs will be ordered by descending count for 
all subjects 
Display of Continuous Statistics 
Means and medians will be shown to one more decimal place and the standard deviation will be shown to two more decimal that the 
source data values. In cases where variables are derived and have floating point values (no fixed number of decimal places), an 
appropriate level of precision will be determined based on the context. 
Statistics that cannot be derived will be shown as a dash ( “-”) in summary tables. 
Two-Sided confidence intervals are displayed with a format such as “(xx.x, xx.x).” If a confidence interval cannot be produced due to 
insufficient data, then a dash (“-”) will be shown in place of the entire confidence interval. 


 
 
 
14 
Display of Percentages 
The following conventions apply for percentages: 
x Percentages will be displayed to one decimal place unless otherwise specified 
x No percentage will be shown if the corresponding count is 0 
x Percentages that are exactly equal to 100% will be displayed as “100%” 
x Percentages that round down to 0.0% will be displayed as “<0.1%” 
x Percentages that round up to 100.0% will be displayed as “>99.9%” 
Percentages are shown in parentheses after the corresponding count such as “25 (  5.2)” where extra spaces are included after the left 
parenthesis to ensure that decimal places for all percentages align within the same column. 
Display of P-Values 
Unless otherwise noted, p-values will be displayed as follows: 
x P-values between 0.0001 and 0.9999 will be displayed in the format “0.xxxx” 
x P-values that are exactly equal to 1 will be displayed as “1.0000” 
x P-values <0.0001 will be displayed as “<0.0001” 
x P-values >0.9999 and not exactly equal to 1 will be displayed as “>0.9999” 
P-values that are descriptive and not associated with a formal test of hypothesis will not be flagged based on statistical significance. 
The following note will be shown in the table: 
Note: P-values are for descriptive purposes and are not evaluated for statistical significance. 
Unless otherwise noted, p-values that are statistically significant will be flagged with an asterisk. The table footnote is dependent on 
the setting, but the following example footnote is appropriate for many settings: 
* Statistically significant at the 0.05 level. 
Display of Dates in Subject Data Listings 
Dates will be shown as follows: 


 
 
 
15 
x DDMMMYYYY for complete dates 
x MMMYYYY for dates with only a month and year 
x YYYY for dates with only a year 
Partial dates are not imputed for subject data listings even if such dates are imputed for statistical algorithms. Relative day (if shown) 
is only derived for complete dates. 
Display of Time in Subject Data Listings 
Time will be shown as follows: 
x HH:MM for complete time 
x HH for time with only hours 
Partial time is not imputed for subject data listings. 
Display of Missing Values in Subject Data Listings 
For subject data listings, missing numeric values will be shown as a dash ( “-”). Missing character values will be shown as blanks. 
 
 
 


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<Final 2.0> 
<date> / <time> / <program name> 
 
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16 
Table 14.1.1.1 Summary of Analysis Sets  
Analysis Set: Full Analysis Set  
Analysis Set  
ARV-471       
200 mg N=XXX 
n (%) 
Anastrozole 
1 mg N=XX 
n (%) 
Total 
N=XXX 
n (%) 
Full Analysis Set [1]     
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
Safety Analysis Set [2]   
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
Ki-67 Evaluable Set [3] 
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
Pharmacodynamic/Biomarker Analysis Set [4]  
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
PK Concentration Analysis Set [5]            
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
 
 
 
 
[1] Full Analysis Set is defined as all enrolled participants who were randomized.  
[2] Safety Analysis Set is defined as all enrolled participants who receive at least 1 dose of study intervention.  
[3] Ki-67 Evaluable Set is defined as all enrolled participants who were randomized and received at least one dose of 
study treatment and had evaluable Ki-67 measurements other than ‘0’ or ‘< 1’ from baseline and evaluable Ki-67 
measurements from C1D15 visits.  
[4] Pharmacodynamic/Biomarker Analysis Set is defined as all enrolled participants with at least 1 of the 
Pharmacodynamic/Biomarkers evaluated at pre and/or post dose.  
[5] PK Concentration Analysis Set includes all participants in the Safety Analysis Set who have at least one plasma 
concentration (including those below the limit of quantification) for ARV-471, or ARV-473.   
Source: Listing 16.2.1.1. 
Date of data extraction: DDMMMYYYY; Date of Creation: DDMMMYYYY. (add this footnote in all TFLs) 
 
Programming Note:  
 
  
 


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<date> / <time> / <program name> 
 
Page xxx of yyy 
 
17 
Table 14.1.1.2 Summary of Participants with Tumor Biospsy  
Analysis Set: Full Analysis Set    
Test: Ki-67  
 
ARV-471       
200 mg N=XXX     
Anastrozole 
1 mg N=XX 
Total 
N=XXX 
At Screen, N’  
XXX 
XXX 
XXX 
   With result, n (%)   
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
   Uninterpretable, n (%) 
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
 
 
 
 
At Cycle 1 Day 15, N’    
XXX 
XXX 
XXX 
   With result, n (%)   
  
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
   Uninterpretable, n (%) 
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
 
 
 
 
At Cycle 6 Day 18, N’  
XXX 
XXX 
XXX 
   With result, n (%)   
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
   Uninterpretable, n (%) 
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
 
 
 
 
At Unscheduled, N’      
XXX 
XXX 
XXX 
   With result, n (%)   
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
   Uninterpretable, n (%) 
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
 
 
 
 
 
 
 
 
Note: N’ is the number of participants at the visit. It is the denominator of the visit. 
Source: Listing 16.2.6.5. 
Date of data extraction: DDMMMYYYY; Date of Creation: DDMMMYYYY. (add this footnote in all TFLs) 
 
Programming Note:  
Repeat the table for each test on a new page. "Test: Progesterone Receptor" 


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Table 14.1.2.1 
Summary of Disposition and Discontinuation  
Analysis Set: Enrolled Participants                  
 
ARV-471 
200 mg N=XXX 
n (%) 
 Anastrozole  
1 mg N=XX 
n (%) 
Total 
N=XXX 
n (%) 
 
 
 
 
Number of Enrolled Participants, N’  
 
 
XXX 
    Number of Screen Failures, N’    
 
 
XX 
    Number of Eligible Participants not Randomized, N’    
 
 
XX 
Number of Participants Randomized (Full Analysis Set),N  
XXX 
XX 
XXX 
   Never Dosed    
X(XX.X) 
X(XX.X) 
X(XX.X) 
   Completed Treatment per Protocol  
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
   ARV-471/Anastrozole Early Discontinuation  
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
 
 
 
 
Reason for ARV-471/Anastrozole Early Discontinuation    
 
 
 
   Disease Progression per Response Criteria 
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
   Clinical Progression 
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
   Withdrawal of Consent 
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
   Significant non-compliance 
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
   Pregnancy 
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
   Death 
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
   Adverse Event 
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
   Study Terminated by Sponsor 
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
   Lost to Follow-up 
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
   Other 
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
 
 
 
 
Completed Study per Protocol  
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
Study Early Discontinuation   
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
 
 
 
 
Reason for Study Early Discontinuation   
 
 
 
   Withdrawal of Consent  
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
   Study Terminated by Sponsor 
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
   Lost to Follow-up 
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
   Death 
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
   Other 
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
 
 
 
 
Note: Enrolled Participants included all subjects who signed the Informed Consent.  
Note: Column N and percentage are based on the number of subjects in Full Analysis Set. 
Source: Listing 16.2.1.2. 
Date of data extraction: DDMMMYYYY; Date of Creation: DDMMMYYYY. 
 


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Repeat the following table with Table 14.1.2.1 shell 
Table 14.1.2.2 
Summary of Disposition and Discontinuation  
Analysis Set: Ki-67 Evaluable Set  


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Table 14.1.3 
Summary of Protocol Deviation  
Analysis Set: Full Analysis Set  
 
 
ARV-471  
200 mg N=XX 
n (%) 
 Anastrozole  
1 mg N=XX 
n (%) 
Total 
N=XXX 
n (%) 
 
 
 
 
 
Number of Subjects with Any Protocol 
Deviation  
 
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
   Informed Consent  
 
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
   IMP/NIMP  
 
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
   Protocol Compliance  
 
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
   Safety  
 
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
   ICH/GCP  
 
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
   <insert> 
 
 
 
 
                        
 
 
 
 
Number of Subjects with Major or 
Critical Protocol Deviation  
 
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
   Informed Consent  
 
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
   IMP/NIMP  
 
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
   Protocol Compliance  
 
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
   Safety  
 
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
   ICH/GCP  
 
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
   <insert> 
 
 
 
 
 
 
 
 
 
Number of Subjects with Minor Protocol 
Deviation  
 
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
   Informed Consent  
 
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
   IMP/NIMP  
 
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
   Protocol Compliance  
 
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
   Safety  
 
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
   ICH/GCP  
 
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
   <insert> 
 
 
 
 
 
 
 
 
 
Source: Listing 16.2.2. 
Date of data extraction: DDMMMYYYY; Date of Creation: DDMMMYYYY. 
 
 
 


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Table 14.1.4.1 
Summary of Demographic Characteristics  
Analysis Set: Full Analysis Set                  
 
ARV-471 
200 mg N=XXX 
 Anastrozole  
1 mg N=XX 
Total 
N=XXX 
 
 
 
 
Sex, n(%) 
 
 
 
   Female  
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
 
 
 
 
Age (years)  
 
 
 
   n 
xxx 
xx 
xx 
   Mean (Standard Deviation) 
xx.x(xx.xx) 
xx.x(xx.xx) 
xx.x(xx.xx) 
   Median 
xx.x 
xx.x 
xx.x 
   Min, Max 
xx, xx 
xx, xx 
xx, xx 
 
 
 
 
Age Group, n(%) 
 
 
 
   ≥ 60 Years 
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
   < 60 Years 
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
 
 
 
 
Race [1], n(%) 
 
 
 
   American Indian or Alaskan Native 
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
   Asian 
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
   Black or African American 
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
   Native Hawaiian/Other Pacific Islander  
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
   White 
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
   Other 
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
   Unknown 
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
 
 
 
 
Ethnicity, n(%) 
 
 
 
   Hispanic or Latino  
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
   Not Hispanic or Latino  
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
   Not Reported 
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
 
 
 
 
Weight (kg) at Baseline  
 
 
 
   n 
xxx 
xx 
xx 
   Mean (Standard Deviation) 
xx.x(xx.xx) 
xx.x(xx.xx) 
xx.x(xx.xx) 
   Median 
xx.x 
xx.x 
xx.x 
   Min, Max 
xx, xx 
xx, xx 
xx, xx 
 
 
 
 
Height (cm) at Baseline   
 
 
 
   n 
xxx 
xx 
xx 
   Mean (Standard Deviation) 
xx.x(xx.xx) 
xx.x(xx.xx) 
xx.x(xx.xx) 
   Median 
xx.x 
xx.x 
xx.x 
   Min, Max 
xx, xx 
xx, xx 
xx, xx 
 
 
 
 


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ECOG Status at Baseline, n(%) 
 
 
 
   0 
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
   1 
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
 
 
 
 
Size of Primary Breast Tumor (T-stage), n(%) 
 
 
 
   ≤ 2 cm 
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
   >2 to < 5 cm 
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
   ≥ 5 cm 
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
 
 
 
 
Post-menopausal Reason, n(%)   
 
 
 
   Prior bilateral oophorectomy 
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
   Age >= 60 years 
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
   Age < 60 years and amenorrhoeic for at least 12 months 
and FSH/estradiol in the postmenopausal range 
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
 
 
 
 
[1] Multiple race might be reported. 
Source: Listing 16.2.4.1. 
Date of data extraction: DDMMMYYYY; Date of Creation: DDMMMYYYY. 
 
Repeat the following table with Table 14.1.4.1 shell 
 
Table 14.1.4.2 
Summary of Demographic Characteristics  
Analysis Set: Ki-67 Evaluable Set  


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Table 14.1.5 
Summary of Medical History by System Organ Class and Preferred Term 
Analysis Set: Full Analysis Set  
 
System Organ Class 
   Preferred Term 
   ARV-471    
200 mg N=XXX 
Anastrozole  
1 mg N=XX 
Total 
N=XXX 
Patients with Medical History, n(%) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
 
 
System Organ Class #1  
 
 
 
 Preferred Term #1  
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 Preferred Term #2 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 <insert> 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
 
 
System Organ Class #2 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 Preferred Term #1 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 Preferred Term #2 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
<insert> 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
 
 
Note: Medical history was coded with MedDRA version 27.0. 
Note: Subjects are counted once per Preferred Term and once per System Organ Class. 
Sources: Listing 16.2.4.2. 
 
 
Programming notes:  
 
 


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Table 14.1.6.1 
Summary of Disease Staging and Disease Characteristics  
Analysis Set: Full Analysis Set  
              
 
ARV-471 
200 mg N=XXX 
 Anastrozole  
1 mg N=XX 
Total 
N=XXX 
 
 
 
 
Time since Initial Diagnosis (months)  
 
 
 
   n 
xxx 
xx 
xx 
   Mean (Standard Deviation) 
xx.x(xx.xx) 
xx.x(xx.xx) 
xx.x(xx.xx) 
   Median 
xx.x 
xx.x 
xx.x 
   Min, Max 
xx, xx 
xx, xx 
xx, xx 
 
 
 
 
Time since Current Staging (months)  
 
 
 
   n 
xxx 
xx 
xx 
   Mean (Standard Deviation) 
xx.x(xx.xx) 
xx.x(xx.xx) 
xx.x(xx.xx) 
   Median 
xx.x 
xx.x 
xx.x 
   Min, Max 
xx, xx 
xx, xx 
xx, xx 
 
 
 
 
Primary Diagnosis: ER+ HER2- Breast Cancer, n(%) 
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
 
 
 
 
Disease Stage at Initial Diagnosis, n(%) 
 
 
 
   Stage 0 
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
   Stage IA 
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
   Stage IB 
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
   Stage IIA 
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
   Stage IIB 
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
   Stage IIIA 
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
   Stage IIIB 
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
   Stage IIIC 
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
   Stage IV 
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
   Unknown 
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
  
 
 
 
Disease Stage at Screening, n(%) 
 
 
 
   Stage 0 
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
   Stage IA 
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
   Stage IB 
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
   Stage IIA 
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
   Stage IIB 
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
   Stage IIIA 
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
   Stage IIIB 
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
   Stage IIIC 
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
   Stage IV 
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
   Unknown 
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
 
 
 
 


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Primary Tumor at Initial Diagnosis, n(%) 
 
 
 
   TX  
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
   T0 
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
   Tis 
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
   T1mi 
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
   T1a 
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
   T1b 
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
   T1c 
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
   T2 
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
   T3 
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
   T4a 
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
   T4b 
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
   T4c 
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
 
 
 
 
Primary Tumor at Screening, n(%) 
 
 
 
   TX  
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
   T0 
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
   Tis 
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
   T1mi 
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
   T1a 
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
   T1b 
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
   T1c 
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
   T2 
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
   T3 
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
   T4a 
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
   T4b 
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
   T4c 
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
 
 
 
 
Imaging Modality for Primary Tumor at Screening, n(%) 
 
 
 
   CT 
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
   MRI 
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
   Ultrasound 
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
   Mammogram 
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
 
 
 
 
Regional Lymph Node at Initial Diagnosis, n(%) 
 
 
 
   cNX 
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
   cN0 
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
   cN1 
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
   cN2a 
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
   cN2b 
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
   cN3a 
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
   cN3b 
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
   cN3c 
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
 
 
 
 


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Regional Lymph Node at Screening, n(%)   
 
 
 
   cNX 
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
   cN0 
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
   cN1 
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
   cN2a 
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
   cN2b 
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
   cN3a 
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
   cN3b 
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
   cN3c 
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
 
 
 
 
Distant Metastasis at Initial Diagnosis, n(%) 
 
 
 
   M0 
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
   M1 
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
   Unknown 
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
 
 
 
 
Distant Metastasis at Screening, n(%) 
 
 
 
   M0 
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
   M1 
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
   Unknown 
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
 
 
 
 
Histopathological Classification at Initial Diagnosis, n(%) 
 
 
 
   In-Situ Carcinoma 
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
   Invasive Ductal Carcinoma 
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
   Invasive Lobular Carcinoma 
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
   Invasive Mixed Ductal and Lobular Breast Carcinoma 
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
   Invasive Carcinoma NOS 
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
   Invasive Adenocarcinoma NOS 
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
   Tubular Carcinoma 
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
   Invasive Mucinous Adenocarcinoma 
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
   Other 
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
 
 
 
 
Histopathological Classification at Screening, n(%) 
 
 
 
   In-Situ Carcinoma 
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
   Invasive Ductal Carcinoma 
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
   Invasive Lobular Carcinoma 
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
   Invasive Mixed Ductal and Lobular Breast Carcinoma 
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
   Invasive Carcinoma NOS 
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
   Invasive Adenocarcinoma NOS 
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
   Tubular Carcinoma 
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
   Invasive Mucinous Adenocarcinoma 
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
   Other 
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
 
 
 
 
 
 
 
 
 
 
 
 


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Histopathological Grade at Initial Diagnosis, n(%)   
 
 
 
   Grade 1 
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
   Grade 2 
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
   Grade 3 
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
   Grade X 
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
 
 
 
 
Histopathological Grade at Screening, n(%) 
 
 
 
   Grade 1 
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
   Grade 2 
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
   Grade 3 
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
   Grade X 
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
 
 
 
 
Planned Type of Breast Surgery, n(%) 
 
 
 
   Breast conserving surgery 
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
   Mastectomy 
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
 
 
 
 
Note: Time since initial diagnosis (months) is defined as time from the date of initial diagnosis to the date of first 
ARV-471/anastrozole dose. Time since current staging (months) is defined as time from the date of current staging to 
the date of first ARV-471/anastrozole dose. 
Source: Listing 16.2.4.3 and Listing 16.2.4.4. 
Date of data extraction: DDMMMYYYY; Date of Creation: DDMMMYYYY. 
 
Programming Note:  
 
 
Repeat the following table with Table 14.1.6.1 shell 
Table 14.1.6.2 
Summary of Disease Staging and Disease Characteristics 
Analysis Set: Ki-67 Evaluable Set  
 


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Table 14.1.7.1 
Summary of Disease Molecular Biology at Baseline  
Analysis Set: Full Analysis Set 
 
ARV-471 
200 mg N=XXX 
 Anastrozole  
1 mg N=XX 
Total 
N=XXX 
 
 
 
 
HER2 Status, Performed, n(%) 
 
 
 
   Yes 
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
   No  
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
 
 
 
 
Sample Site of HER2 Status, n(%) 
 
 
 
   Breast 
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
   Lymph Node 
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
   Other 
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
 
 
 
 
HER2 Analytical Method, n(%) 
 
 
 
   Immunohistochemistry (IHC) 
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
   In Situ Hybridization (ISH) 
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
 
 
 
 
HER2 Analytical Result, n(%) 
 
 
 
   0 
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
   1+ 
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
   2+ 
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
   3+ 
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
 
 
 
 
   Positive 
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
   Negative 
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
   Unknown 
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
 
 
 
 
Ki67, Performed, n(%) 
 
 
 
   Yes 
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
   No  
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
 
 
 
 
Sample Site of Ki67, n(%) 
 
 
 
   Breast 
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
   Lymph Node 
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
   Other 
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
 
 
 
 
% of Tumor Cells with Ki67 (Local)  
 
 
 
   n 
xxx 
xx 
Xx 
   Mean (Standard Deviation) 
xx.x(xx.xx) 
xx.x(xx.xx) 
xx.x(xx.xx) 
   Median 
xx.x 
xx.x 
xx.x 
   Min, Max 
xx, xx 
xx, xx 
xx, xx 
 
 
 
 
 
 
 
 


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   < 20%, n(%) 
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
   ≥ 20%, n(%)   
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
 
 
 
 
% of Tumor Cells with Ki67 (Central)  
 
 
 
   n 
xxx 
xx 
Xx 
   Mean (Standard Deviation) 
xx.x(xx.xx) 
xx.x(xx.xx) 
xx.x(xx.xx) 
   Median 
xx.x 
xx.x 
xx.x 
   Min, Max 
xx, xx 
xx, xx 
xx, xx 
 
 
 
 
   < 20%, n(%) 
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
   ≥ 20%, n(%)   
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
 
 
 
 
Estrogen Receptor, Performed,  n(%) 
 
 
 
   Yes 
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
   No  
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
 
 
 
 
Sample Site of Estrogen Receptor, n(%) 
 
 
 
   Breast 
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
   Lymph Node 
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
   Other 
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
 
 
 
 
% of Tumor Cells with Estrogen Receptor (Local)  
 
 
 
   n 
xxx 
xx 
Xx 
   Mean (Standard Deviation) 
xx.x(xx.xx) 
xx.x(xx.xx) 
xx.x(xx.xx) 
   Median 
xx.x 
xx.x 
xx.x 
   Min, Max 
xx, xx 
xx, xx 
xx, xx 
 
 
 
 
   < 10%, n(%) 
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
   ≥ 10%, n(%)   
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
 
 
 
 
Progesterone Receptor, Performed , n(%) 
 
 
 
   Yes 
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
   No  
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
 
 
 
 
Sample Site of Progesterone Receptor, n(%) 
 
 
 
   Breast 
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
   Lymph Node 
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
   Other 
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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% of Tumor Cells with Progesterone Receptor (Local)  
 
 
 
   n 
xxx 
xx 
Xx 
   Mean (Standard Deviation) 
xx.x(xx.xx) 
xx.x(xx.xx) 
xx.x(xx.xx) 
   Median 
xx.x 
xx.x 
xx.x 
   Min, Max 
xx, xx 
xx, xx 
xx, xx 
 
 
 
 
   < 1%, n(%) 
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
   ≥ 1%, n(%)   
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
 
 
 
 
Note: All the data are from local laboratories unless otherwise indicated. 
Source: Listing 16.2.4.5. 
Date of data extraction: DDMMMYYYY; Date of Creation: DDMMMYYYY. 
 
Programming Note:  
 
 
Repeat the following table with Table 14.1.7.1 shell 
 
Table 14.1.7.2 
Summary of Disease Molecular Biology at Baseline 
Analysis Set: Ki-67 Evaluable Set  
 
 
 


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Table 14.1.8 
Summary of Prior Cancer Related Surgery/Biopsy  
Analysis Set: Full Analysis Set    
 
ARV-471 
200 mg N=XXX 
 Anastrozole  
1 mg N=XX 
Total 
N=XXX 
 
 
 
 
Any Prior Surgery/Biopsy Related to Trial Disease[1], n(%) 
 
 
 
   Yes 
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
 
 
 
 
Procedure[1], n(%) 
 
 
 
   Sentinel node biopsy 
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
   Axillary sampling 
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
   Fine needle aspiration, 
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
   Core needle biopsy 
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
   Other 
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
 
 
 
 
Procedure Location[1], n(%) 
 
 
 
   Breast 
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
   Lymph node 
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
   Other 
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
 
 
 
 
Laterality[1], n(%) 
 
 
 
   Left 
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
   Right 
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
   Bilateral 
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
   Not applicable 
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
 
 
 
 
Time since Most Recent Surgery/Biopsy (months) 
 
 
 
   n 
xxx 
xx 
Xxx 
   Mean  
xx.x 
xx.x 
xx.x 
   Standard Deviation 
xx.xx 
xx.xx 
xx.xx 
   Median 
xx.x 
xx.x 
xx.x 
   Min, Max 
xx, xx 
xx, xx 
xx, xx 
 
 
 
 
Note: Time since most recent surgery/biopsy is defined as time from the most recent date of surgery to the date of 
first ARV-471/Anastrozole dose. 
[1] A subject might receive multiple Surgery/Biopsy. 
Date of data extraction: DDMMMYYYY; Date of Creation: DDMMMYYYY. 
 
 
 


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Table 14.1.9 
Summary of Prior Medication Analysis Set: Full Analysis Set  
ATC level 2  
  Preferred Name 
ARV-471      
200 mg N=XXX 
 
Anastrozole  
1 mg N=XX 
Total 
N=XXX 
 
 
 
 
Subjects with Any Prior Medication, n(%)   
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
 
 
 
 
ATC level 2 1     
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
  Preferred Name 1  
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
  Preferred Name 2 
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
 
 
 
 
ATC level 2 2 
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
  Preferred Name 1  
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
  Preferred Name 2 
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
 
 
 
 
Note: Prior medications are coded according to the World Health Organization drug dictionary (WHO-Drug B3 Global version 
September 2024).  
Note: Prior medications include non-study drug medications that are ended before Day 1.  
Source: Listing 16.2.4.6. 
Date of data extraction: DDMMMYYYY; Date of Creation: DDMMMYYYY. 
 
Programming Note:  
 


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33 
Table 14.1.10 
Summary of Concomitant Medication Analysis Set: Full Analysis Set                    
ATC level 2  
  Preferred Name 
ARV-471 
200 mg N=XXX 
 Anastrozole  
1 mg N=XX 
Total 
N=XXX 
 
 
 
 
Subjects with Any Concomitant Medication, n(%) 
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
 
 
 
 
ATC level 2 1   
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
  Preferred Name 1  
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
  Preferred Name 2 
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
 
 
 
 
ATC level 2 2 
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
  Preferred Name 1  
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
  Preferred Name 2 
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
 
 
 
 
Note: Prior medications are coded according to the World Health Organization drug dictionary (WHO-Drug B3 Global version 
September 2024).  
Note: Concomitant medications include non-study drug medications that are used/started on/after Day 1 and within 30 days 
from the last administration of the study intervention (ie, study drug treatment or surgical resection, whichever occurs 
last).  
Source: Listing 16.2.4.6. 
Date of data extraction: DDMMMYYYY; Date of Creation: DDMMMYYYY. 
 
Programming Note:  
 
 
 


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34 
Table 14.1.11 
Summary of ARV-471 and Anastrozole Compliance and Exposure  
Analysis Set: Safety Analysis Set  
 
ARV-471 
200 mg N=XXX 
 Anastrozole  
1 mg N=XX 
 
 
 
Duration of Treatment (week)   
 
 
   n 
xxx 
xx 
   Mean (Standard Deviation) 
xx.x(xx.xx) 
xx.x(xx.xx) 
   Median 
xx.x 
xx.x 
   Min, Max 
xx, xx 
xx, xx 
 
 
 
Cumulative Dose (mg)          
 
 
   n 
xxx 
xx 
   Mean (Standard Deviation) 
xx.x(xx.xx) 
xx.x(xx.xx) 
   Median 
xx.x 
xx.x 
   Min, Max 
xx, xx 
xx, xx 
 
 
 
Absolute Dose Intensity (mg/week)       
 
 
   n 
xxx 
xx 
   Mean (Standard Deviation) 
xx.x(xx.xx) 
xx.x(xx.xx) 
   Median 
xx.x 
xx.x 
   Min, Max 
xx, xx 
xx, xx 
 
 
 
Total Planned Dose (mg)       
 
 
   n 
xxx 
xx 
   Mean (Standard Deviation) 
xx.x(xx.xx) 
xx.x(xx.xx) 
   Median 
xx.x 
xx.x 
   Min, Max 
xx, xx 
xx, xx 
 
 
 
Compliance (%)             
 
 
   n 
xxx 
xx 
   Mean (Standard Deviation) 
xx.x(xx.xx) 
xx.x(xx.xx) 
   Median 
xx.x 
xx.x 
   Min, Max 
xx, xx 
xx, xx 
 
 
 
Number (%) of Compliant Patients, n(%)  
XXX(XX.X) 
XX(XX.X) 
 
 
 
Relative Dose Intensity (%)       
 
 
   n 
xxx 
xx 
   Mean (Standard Deviation) 
xx.x(xx.xx) 
xx.x(xx.xx) 
   Median 
xx.x 
xx.x 
   Min, Max 
xx, xx 
xx, xx 
 
 
 


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Number of Subjects with at Least One Action Taken, n(%) 
XXX(XX.X) 
XX(XX.X) 
   Dose Interrupted     
XXX(XX.X) 
XX(XX.X) 
   Dose Discontinued  
XXX(XX.X) 
XX(XX.X) 
   Dose Reduced 
XXX(XX.X) 
XX(XX.X) 
   Dose Increased  
XXX(XX.X) 
XX(XX.X) 
 
 
 
Reason for Dose Interrupted[1], n(%)   
 
 
   Adverse event  
XXX(XX.X) 
XX(XX.X) 
   Participant missed/Skipped dose 
XXX(XX.X) 
XX(XX.X) 
   Medication error 
XXX(XX.X) 
XX(XX.X) 
   Other 
XXX(XX.X) 
XX(XX.X) 
 
 
 
Reason for Dose Reduced[1], n(%)  
 
 
   Adverse event       
XXX(XX.X) 
XX(XX.X) 
   Participant missed/Skipped dose 
XXX(XX.X) 
XX(XX.X) 
   Medication error 
XXX(XX.X) 
XX(XX.X) 
   Other 
XXX(XX.X) 
XX(XX.X) 
 
 
 
Reason for Dose Discontinued[1], n(%)  
 
 
   Adverse event       
XXX(XX.X) 
XX(XX.X) 
   Participant missed/Skipped dose 
XXX(XX.X) 
XX(XX.X) 
   Medication error 
XXX(XX.X) 
XX(XX.X) 
   Other 
XXX(XX.X) 
XX(XX.X) 
 
 
 
Reason for Dose Increased[1], n(%)  
 
 
   Adverse event       
XXX(XX.X) 
XX(XX.X) 
   Participant missed/Skipped dose 
XXX(XX.X) 
XX(XX.X) 
   Medication error 
XXX(XX.X) 
XX(XX.X) 
   Other 
XXX(XX.X) 
XX(XX.X) 
 
 
 
[1] Multiple reasons might be reported. 
Note: Compliance is 100*(Total cumulative dose/Total planned dose), accounting for planned dose modifications and 
interruptions. Compliant Patients are those with compliance >= 80% - <= 120%. Absolute Dose Intensity (mg/week)is 
(Cumulative Dose (mg))/(Duration of Treatment (week)). Relative Dose Intesity (%) is 100*(Absolute Dose Intensity 
(mg/week))/(Initial Planned  Weekly Dose (mg/week), 1400 mg/week for ARV-471 and 7 mg/week for Anastrozole)). 
Source: Listing 16.2.5.1, and Listing 16.2.5.2. 
Date of data extraction: DDMMMYYYY; Date of Creation: DDMMMYYYY. 
Programming Note:  
 
 
 


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36 
Table 14.2.1.1.1 
Summary of Ki-67 Percentage Change from Baseline at C1D15 with Central Ki-67 as a Covariate  
Analysis Set: Ki-67 Evaluable Set              
                               
ARV-471 
200 mg N=XXX 
 Anastrozole  
1 mg N=XX 
Difference 
log(Ki-67 at baseline)  
 
 
 
   n 
xxx 
xx 
 
   Mean (Standard Deviation) 
xx.x(xx.xx) 
xx.x(xx.xx) 
 
   Median 
xx.x 
xx.x 
 
   Min, Max 
xx, xx 
xx, xx 
 
 
 
 
 
log(Ki-67 at C1D15)  
 
 
 
   n 
xxx 
xx 
 
   Mean (Standard Deviation) 
xx.x(xx.xx) 
xx.x(xx.xx) 
 
   Median 
xx.x 
xx.x 
 
   Min, Max 
xx, xx 
xx, xx 
 
 
 
 
 
log(Ki-67 at C1D15) - log(Ki-67 at baseline)  
 
 
 
   n 
xxx 
xx 
 
   Mean (Standard Deviation) 
xx.x(xx.xx) 
xx.x(xx.xx) 
 
   Median 
xx.x 
xx.x 
 
   Min, Max 
xx, xx 
xx, xx 
 
   LSM (Standard Error)[1]  
xx.x(xx.xx) 
xx.x(xx.xx) 
xx.x(xx.xx) 
   80% Confidence Interval for LSM[1]  
xx.xx, xx.xx 
xx.xx, xx.xx 
 
   95% Confidence Interval for LSM[1] 
xx.xx, xx.xx 
xx.xx, xx.xx 
 
   80% Confidence Interval for LSM Difference[1] 
 
 
xx.xx, xx.xx 
   95% Confidence Interval for LSM Difference[1] 
 
 
xx.xx, xx.xx 
 
 
 
 
Ratio between Ki-67 at C1D15 and Ki-67 at baseline  
 
 
 
   Geometric Means[2]  
xx.x 
xx.x 
xx.x 
   80% Confidence Interval for Geometric Means[2] 
xx.xx, xx.xx 
xx.xx, xx.xx 
 
   95% Confidence Interval for Geometric Means[2] 
xx.xx, xx.xx 
xx.xx, xx.xx 
 
   80% Confidence Interval for Geometric Means Difference[2] 
 
 
xx.xx, xx.xx 
   95% Confidence Interval for Geometric Means Difference[2] 
 
 
xx.xx, xx.xx 
 
 
 
 
Note: The endpoint is the ratio between the Ki-67 measurements obtained from C1D15 visit and baseline, which will be 
derived as = exp(log(Ki-67 at C1D15) - log(Ki-67 at baseline)). 
[1] Analysis based on an analysis of covariance (ANCOVA) model with baseline Ki-67 score (assessed centrally: <20% vs 
≥20%), the tumor size (≤2 cm, >2 to <5 cm, or ≥5 cm) as covariates for treatment. Baseline Ki-67 score and/or the tumor 
size categories are derived based on data collected instead of data reported in IRT. 
[2] Back transformed values of [1]. 
Source: Listing 16.2.6.1. 
Date of data extraction: DDMMMYYYY; Date of Creation: DDMMMYYYY.  
 
 


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Table 14.2.1.1.2 
Summary of Ki-67 Percentage Change from Baseline at C1D15 with Local Ki-67 as a Covariate 
Analysis Set: Ki-67 Evaluable Set  
 
ARV-471 
200 mg N=XXX 
 Anastrozole  
1 mg N=XX 
Difference 
log(Ki-67 at baseline)  
 
 
 
   n 
xxx 
xx 
 
   Mean (Standard Deviation) 
xx.x(xx.xx) 
xx.x(xx.xx) 
 
   Median 
xx.x 
xx.x 
 
   Min, Max 
xx, xx 
xx, xx 
 
 
 
 
 
log(Ki-67 at C1D15)  
 
 
 
   n 
xxx 
xx 
 
   Mean (Standard Deviation) 
xx.x(xx.xx) 
xx.x(xx.xx) 
 
   Median 
xx.x 
xx.x 
 
   Min, Max 
xx, xx 
xx, xx 
 
 
 
 
 
log(Ki-67 at C1D15) - log(Ki-67 at baseline) 
 
 
 
   n 
xxx 
xx 
 
   Mean (Standard Deviation) 
xx.x(xx.xx) 
xx.x(xx.xx) 
 
   Median 
xx.x 
xx.x 
 
   Min, Max 
xx, xx 
xx, xx 
 
   LSM (Standard Error)[1]  
xx.x(xx.xx) 
xx.x(xx.xx) 
xx.x(xx.xx) 
   80% Confidence Interval for LSM[1] 
xx.xx, xx.xx 
xx.xx, xx.xx 
 
   95% Confidence Interval for LSM[1] 
xx.xx, xx.xx 
xx.xx, xx.xx 
 
   80% Confidence Interval for LSM Difference[1] 
 
 
xx.xx, xx.xx 
   95% Confidence Interval for LSM Difference[1] 
 
 
xx.xx, xx.xx 
 
 
 
 
Ratio between Ki-67 at C1D15 and Ki-67 at baseline 
 
 
 
 
   Geometric Means[2]  
xx.x 
xx.x 
xx.x 
   80% Confidence Interval for Geometric Means[2] 
xx.xx, xx.xx 
xx.xx, xx.xx 
 
   95% Confidence Interval for Geometric Means[2] 
xx.xx, xx.xx 
xx.xx, xx.xx  
 
   80% Confidence Interval for Geometric Means Difference[2] 
 
 
xx.xx, xx.xx 
   95% Confidence Interval for Geometric Means Difference[2] 
 
 
xx.xx, xx.xx 
Note: The endpoint is the ratio between the Ki-67 measurements obtained from C1D15 visit and baseline, which will be 
derived as = exp(log(Ki-67 at C1D15) - log(Ki-67 at baseline)). 
[1] Analysis based on an analysis of covariance (ANCOVA) model with baseline Ki-67 score (assessed locally: <20% vs 
≥20%), the tumor size (≤2 cm, >2 to <5 cm, or ≥5 cm) as covariates for treatment. Baseline Ki-67 score and/or the tumor 
size categories are derived based on data collected instead of data reported in IRT. 
[2] Back transformed values of [1]. 
Source: Listing 16.2.6.1. 
Date of data extraction: DDMMMYYYY; Date of Creation: DDMMMYYYY. 
 


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Table 14.2.1.1.3 
Summary of Ki-67 Percentage Change from Baseline at C1D15 without Covariate   
Analysis Set: Ki-67 Evaluable Set  
 
ARV-471 
200 mg N=XXX 
 Anastrozole  
1 mg N=XX 
Difference 
log(Ki-67 at baseline)  
 
 
 
   n 
xxx 
xx 
 
   Mean (Standard Deviation) 
xx.x(xx.xx) 
xx.x(xx.xx) 
 
   Median 
xx.x 
xx.x 
 
   Min, Max 
xx, xx 
xx, xx 
 
 
 
 
 
log(Ki-67 at C1D15)  
 
 
 
   n 
xxx 
xx 
 
   Mean (Standard Deviation) 
xx.x(xx.xx) 
xx.x(xx.xx) 
 
   Median 
xx.x 
xx.x 
 
   Min, Max 
xx, xx 
xx, xx 
 
 
 
 
 
log(Ki-67 at C1D15) - log(Ki-67 at baseline) 
 
 
 
   n 
xxx 
xx 
 
   Mean (Standard Deviation) 
xx.x(xx.xx) 
xx.x(xx.xx) 
 
   Median 
xx.x 
xx.x 
 
   Min, Max 
xx, xx 
xx, xx 
 
   LSM (Standard Error)[1]  
xx.x(xx.xx) 
xx.x(xx.xx) 
xx.x(xx.xx) 
   80% Confidence Interval for LSM[1] 
xx.xx, xx.xx 
xx.xx, xx.xx 
 
   95% Confidence Interval for LSM[1] 
xx.xx, xx.xx 
xx.xx, xx.xx 
 
   80% Confidence Interval for LSM Difference[1] 
 
 
xx.xx, xx.xx 
   95% Confidence Interval for LSM Difference[1] 
 
 
xx.xx, xx.xx 
 
 
 
 
Ratio between Ki-67 at C1D15 and Ki-67 at baseline 
 
 
 
 
   Geometric Means[2]  
xx.x 
xx.x 
xx.x 
   80% Confidence Interval for Geometric Means[2] 
xx.xx, xx.xx 
xx.xx, xx.xx 
 
   95% Confidence Interval for Geometric Means[2] 
xx.xx, xx.xx 
xx.xx, xx.xx  
 
   80% Confidence Interval for Geometric Means Difference[2] 
 
 
xx.xx, xx.xx 
   95% Confidence Interval for Geometric Means Difference[2] 
 
 
xx.xx, xx.xx 
 
 
 
 
Note: The endpoint is the ratio between the Ki-67 measurements obtained from C1D15 visit and baseline, which will be 
derived as = exp(log(Ki-67 at C1D15) - log(Ki-67 at baseline)). 
[1] Analysis based on an analysis of variance (ANOVA) model. 
[2] Back transformed values of [1]. 
Source: Listing 16.2.6.1. 


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Table 14.2.1.2.1 
Summary of Ki-67 Percentage Change from Baseline at C1D15– Subgroup Analysis by Tumor Size   
Analysis Set: Ki-67 Evaluable Set 
Tumor Size: ≤2 cm   
 
ARV-471      
200 mg N=XXX 
 Anastrozole  
1 mg N=XX 
Difference 
log(Ki-67 at baseline)  
 
 
 
   n 
xxx 
xx 
 
   Mean (Standard Deviation) 
xx.x(xx.xx) 
xx.x(xx.xx) 
 
   Median 
xx.x 
xx.x 
 
   Min, Max 
xx, xx 
xx, xx 
 
 
 
 
 
log(Ki-67 at C1D15)  
 
 
 
   n 
xxx 
xx 
 
   Mean (Standard Deviation) 
xx.x(xx.xx) 
xx.x(xx.xx) 
 
   Median 
xx.x 
xx.x 
 
   Min, Max 
xx, xx 
xx, xx 
 
 
 
 
 
log(Ki-67 at C1D15) - log(Ki-67 at baseline) 
 
 
 
   n 
xxx 
xx 
 
   Mean (Standard Deviation) 
xx.x(xx.xx) 
xx.x(xx.xx) 
 
   Median 
xx.x 
xx.x 
 
   Min, Max 
xx, xx 
xx, xx 
 
   LSM (Standard Error)[1] 
xx.x(xx.xx) 
xx.x(xx.xx) 
xx.x(xx.xx) 
   80% Confidence Interval for LSM[1] 
xx.xx, xx.xx 
xx.xx, xx.xx 
 
   95% Confidence Interval for LSM[1] 
xx.xx, xx.xx 
xx.xx, xx.xx 
 
   80% Confidence Interval for LSM Difference[1] 
 
 
xx.xx, xx.xx 
   95% Confidence Interval for LSM Difference[1] 
 
 
xx.xx, xx.xx 
 
 
 
 
Ratio between Ki-67 at C1D15 and Ki-67 at baseline 
 
 
 
   Geometric Means[2] 
xx.x 
xx.x 
xx.x 
   80% Confidence Interval for Geometric Means[2] 
xx.xx, xx.xx 
xx.xx, xx.xx 
 
   95% Confidence Interval for Geometric Means[2] 
xx.xx, xx.xx 
xx.xx, xx.xx 
 
   80% Confidence Interval for Geometric Means Difference[2] 
 
 
xx.xx, xx.xx 
   95% Confidence Interval for Geometric Means Difference[2] 
 
 
xx.xx, xx.xx 
 
 
 
 
Note: The endpoint is the ratio between the Ki-67 measurements obtained from C1D15 visit and baseline, which will be 
derived as = exp(log(Ki-67 at C1D15) - log(Ki-67 at baseline)). 
Note: Baseline tumor size categories are derived based on data collected instead of data reported in IRT. 
[1] Analysis based on an analysis of variance (ANOVA) model. 
[2] Back transformed values of [1]. 
Source: Listing 16.2.6.1. 
Programming Note:  


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Repeat the table for ‘Tumor Size: >2 to <5 cm’, and ‘Tumor Size: ≥5 cm’ on new page. 
 


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41 
Table 14.2.1.2.2  
Summary of Ki-67 Percentage Change from Baseline at C1D15 – Subgroup Analysis by Local Ki-67 Baseline Score  
Analysis Set: Ki-67 Evaluable Set  
Local Ki-67 Baseline Score: < 20%  
 
ARV-471 
200 mg N=XXX 
 Anastrozole  
1 mg N=XX 
Difference 
log(Ki-67 at baseline)  
 
 
 
   n 
xxx 
xx 
 
   Mean (Standard Deviation) 
xx.x(xx.xx) 
xx.x(xx.xx) 
 
   Median 
xx.x 
xx.x 
 
   Min, Max 
xx, xx 
xx, xx 
 
 
 
 
 
log(Ki-67 at C1D15) 
 
 
 
   n 
xxx 
xx 
 
   Mean (Standard Deviation) 
xx.x(xx.xx) 
xx.x(xx.xx) 
 
   Median 
xx.x 
xx.x 
 
   Min, Max 
xx, xx 
xx, xx 
 
 
 
 
 
log(Ki-67 at C1D15) - log(Ki-67 at baseline) 
 
 
 
   n  
xxx 
xx 
 
   Mean (Standard Deviation) 
xx.x(xx.xx) 
xx.x(xx.xx) 
 
   Median 
xx.x 
xx.x 
 
   Min, Max 
xx, xx 
xx, xx 
 
   LSM (Standard Error)[1] 
xx.x(xx.xx) 
xx.x(xx.xx) 
xx.x(xx.xx) 
   80% Confidence Interval for LSM[1] 
xx.xx, xx.xx 
xx.xx, xx.xx 
 
   95% Confidence Interval for LSM[1] 
xx.xx, xx.xx 
xx.xx, xx.xx 
 
   80% Confidence Interval for LSM Difference[1] 
 
 
xx.xx, xx.xx 
   95% Confidence Interval for LSM Difference[1] 
 
 
xx.xx, xx.xx 
 
 
 
 
Ratio between Ki-67 at C1D15 and Ki-67 at baseline 
 
 
 
   Geometric Means[2]  
xx.x 
xx.x 
xx.x 
   80% Confidence Interval for Geometric Means[2] 
xx.xx, xx.xx 
xx.xx, xx.xx 
 
   95% Confidence Interval for Geometric Means[2] 
xx.xx, xx.xx 
xx.xx, xx.xx 
 
   80% Confidence Interval for Geometric Means Difference[2] 
 
 
xx.xx, xx.xx 
   95% Confidence Interval for Geometric Means Difference[2] 
 
 
xx.xx, xx.xx 
 
 
 
 
Note: The endpoint is the ratio between the Ki-67 measurements obtained from C1D15 visit and baseline, which will be 
derived as = exp(log(Ki-67 at C1D15) - log(Ki-67 at baseline)). 
Note: Baseline Ki-67 score are derived based on data collected instead of data reported in IRT. 
[1] Analysis based on an analysis of variance (ANOVA) model. 
[2] Back transformed values of [1]. 
Source: Listing 16.2.6.1. 
Programming Note:  


Arvinas Estrogen Receptor, Inc (Arvinas) 
 
 
CONFIDENTIAL 
ARV-471-BC-201 
 
<Final 2.0> 
<date> / <time> / <program name> 
 
Page xxx of yyy 
 
42 
Repeat the table for ‘Local Ki-67 Baseline Score: ≥ 20%” on new page. 
Table 14.2.1.2.3 
Summary of Ki-67 Percentage Change from Baseline at C1D15– Subgroup Analysis by Central Ki-67 Baseline Score of 20%  
Analysis Set: Ki-67 Evaluable Set  
Central Ki-67 Baseline Score: < 20%  
 
ARV-471 
200 mg N=XXX 
 Anastrozole  
1 mg N=XX 
Difference 
log(Ki-67 at baseline) 
 
 
 
   n 
xxx 
xx 
 
   Mean (Standard Deviation) 
xx.x(xx.xx) 
xx.x(xx.xx) 
 
   Median 
xx.x 
xx.x 
 
   Min, Max 
xx, xx 
xx, xx 
 
 
 
 
 
log(Ki-67 at C1D15)  
 
 
 
   n 
xxx 
xx 
 
   Mean (Standard Deviation) 
xx.x(xx.xx) 
xx.x(xx.xx) 
 
   Median 
xx.x 
xx.x 
 
   Min, Max 
xx, xx 
xx, xx 
 
 
 
 
 
log(Ki-67 at C1D15) - log(Ki-67 at baseline) 
 
 
 
   n  
xxx 
xx 
 
   Mean (Standard Deviation) 
xx.x(xx.xx) 
xx.x(xx.xx) 
 
   Median 
xx.x 
xx.x 
 
   Min, Max 
xx, xx 
xx, xx 
 
   LSM (Standard Error)[1] 
xx.x(xx.xx) 
xx.x(xx.xx) 
xx.x(xx.xx) 
   80% Confidence Interval for LSM[1] 
xx.xx, xx.xx 
xx.xx, xx.xx 
 
   95% Confidence Interval for LSM[1] 
xx.xx, xx.xx 
xx.xx, xx.xx 
 
   80% Confidence Interval for LSM Difference[1] 
 
 
xx.xx, xx.xx 
   95% Confidence Interval for LSM Difference[1] 
 
 
xx.xx, xx.xx 
 
 
 
 
Ratio between Ki-67 at C1D15 and Ki-67 at baseline 
 
 
 
   Geometric Means[2]  
xx.x 
xx.x 
xx.x 
   80% Confidence Interval for Geometric Means[2] 
xx.xx, xx.xx 
xx.xx, xx.xx 
 
   95% Confidence Interval for Geometric Means[2] 
xx.xx, xx.xx 
xx.xx, xx.xx 
 
   80% Confidence Interval for Geometric Means Difference[2] 
 
 
xx.xx, xx.xx 
   95% Confidence Interval for Geometric Means Difference[2] 
 
 
xx.xx, xx.xx 
 
 
 
 
Note: The endpoint is the ratio between the Ki-67 measurements obtained from C1D15 visit and baseline, which will be derived as = 
exp(log(Ki-67 at C1D15) - log(Ki-67 at baseline)). 
Note: Baseline Ki-67 score are derived based on data collected instead of data reported in IRT.[1] Analysis based on an analysis of 
variance (ANOVA) model. 
[2] Back transformed values of [1]. 
Source: Listing 16.2.6.1. 


Arvinas Estrogen Receptor, Inc (Arvinas) 
 
 
CONFIDENTIAL 
ARV-471-BC-201 
 
<Final 2.0> 
<date> / <time> / <program name> 
 
Page xxx of yyy 
 
43 
Programming Note:  
Repeat the table for ‘Central Ki-67 Baseline Score: ≥ 20%” on new page. 
 
 


Arvinas Estrogen Receptor, Inc (Arvinas) 
 
 
CONFIDENTIAL 
ARV-471-BC-201 
 
<Final 2.0> 
<date> / <time> / <program name> 
 
Page xxx of yyy 
 
44 
Table 14.2.1.2.4 
Summary of Ki-67 Percentage Change from Baseline at C1D15 – Subgroup Analysis by Central Ki-67 Baseline Score of 5%  
Analysis Set: Ki-67 Evaluable Set  
Central Ki-67 Baseline Score: < 5%  
 
ARV-471 
200 mg N=XXX 
 Anastrozole  
1 mg N=XX 
Difference 
log(Ki-67 at baseline) 
 
 
 
   n 
xxx 
xx 
 
   Mean (Standard Deviation) 
xx.x(xx.xx) 
xx.x(xx.xx) 
 
   Median 
xx.x 
xx.x 
 
   Min, Max 
xx, xx 
xx, xx 
 
 
 
 
 
log(Ki-67 at C1D15)  
 
 
 
   n 
xxx 
xx 
 
   Mean (Standard Deviation) 
xx.x(xx.xx) 
xx.x(xx.xx) 
 
   Median 
xx.x 
xx.x 
 
   Min, Max 
xx, xx 
xx, xx 
 
 
 
 
 
log(Ki-67 at C1D15) - log(Ki-67 at baseline) 
 
 
 
   n  
xxx 
xx 
 
   Mean (Standard Deviation) 
xx.x(xx.xx) 
xx.x(xx.xx) 
 
   Median 
xx.x 
xx.x 
 
   Min, Max 
xx, xx 
xx, xx 
 
   LSM (Standard Error)[1] 
xx.x(xx.xx) 
xx.x(xx.xx) 
xx.x(xx.xx) 
   80% Confidence Interval for LSM[1] 
xx.xx, xx.xx 
xx.xx, xx.xx 
 
   95% Confidence Interval for LSM[1] 
xx.xx, xx.xx 
xx.xx, xx.xx 
 
   80% Confidence Interval for LSM Difference[1] 
 
 
xx.xx, xx.xx 
   95% Confidence Interval for LSM Difference[1] 
 
 
xx.xx, xx.xx 
 
 
 
 
Ratio between Ki-67 at C1D15 and Ki-67 at baseline 
 
 
 
   Geometric Means[2]  
xx.x 
xx.x 
xx.x 
   80% Confidence Interval for Geometric Means[2] 
xx.xx, xx.xx 
xx.xx, xx.xx 
 
   95% Confidence Interval for Geometric Means[2] 
xx.xx, xx.xx 
xx.xx, xx.xx 
 
   80% Confidence Interval for Geometric Means Difference[2] 
 
 
xx.xx, xx.xx 
   95% Confidence Interval for Geometric Means Difference[2] 
 
 
xx.xx, xx.xx 
 
 
 
 
Note: The endpoint is the ratio between the Ki-67 measurements obtained from C1D15 visit and baseline, which will be 
derived as = exp(log(Ki-67 at C1D15) - log(Ki-67 at baseline)). 
Note: Baseline Ki-67 score are derived based on data collected instead of data reported in IRT. 
[1] Analysis based on an analysis of variance (ANOVA) model. 
[2] Back transformed values of [1]. 
Source: Listing 16.2.6.1. 
Programming Note:  


Arvinas Estrogen Receptor, Inc (Arvinas) 
 
 
CONFIDENTIAL 
ARV-471-BC-201 
 
<Final 2.0> 
<date> / <time> / <program name> 
 
Page xxx of yyy 
 
45 
Repeat the table for ‘Central Ki-67 Baseline Score: ≥ 5%” on new page. 
 


Arvinas Estrogen Receptor, Inc (Arvinas) 
 
 
CONFIDENTIAL 
ARV-471-BC-201 
 
<Final 2.0> 
<date> / <time> / <program name> 
 
Page xxx of yyy 
 
46 
Table 14.2.1.3.1 
Summary of Ki-67 Percentage Change from Baseline at Surgery with Central Ki-67 as a Covariate  
Analysis Set: Full Analysis Set 
 
 
 
ARV-471 
200 mg N=XXX 
 Anastrozole  
1 mg N=XX 
Difference 
log(Ki-67 at baseline)  
 
 
 
   n 
xxx 
xx 
 
   Mean (Standard Deviation) 
xx.x(xx.xx) 
xx.x(xx.xx) 
 
   Median 
xx.x 
xx.x 
 
   Min, Max 
xx, xx 
xx, xx 
 
 
 
 
 
log(Ki-67 at Surgery)  
 
 
 
   n 
xxx 
xx 
 
   Mean (Standard Deviation) 
xx.x(xx.xx) 
xx.x(xx.xx) 
 
   Median 
xx.x 
xx.x 
 
   Min, Max 
xx, xx 
xx, xx 
 
 
 
 
 
log(Ki-67 at Surgery) - log(Ki-67 at baseline) 
 
 
 
   n 
xxx 
xx 
 
   Mean (Standard Deviation) 
xx.x(xx.xx) 
xx.x(xx.xx) 
 
   Median 
xx.x 
xx.x 
 
   Min, Max 
xx, xx 
xx, xx 
 
   LSM (Standard Error)[1]  
xx.x(xx.xx) 
xx.x(xx.xx) 
xx.x(xx.xx) 
   80% Confidence Interval for LSM[1] 
xx.xx, xx.xx 
xx.xx, xx.xx 
 
   95% Confidence Interval for LSM[1] 
xx.xx, xx.xx 
xx.xx, xx.xx 
 
   80% Confidence Interval for LSM Difference[1] 
 
 
xx.xx, xx.xx 
   95% Confidence Interval for LSM Difference[1] 
 
 
xx.xx, xx.xx 
 
 
 
 
Ratio between Ki-67 at Surgery and Ki-67 at baseline 
 
 
 
   Geometric Means[2] 
xx.x 
xx.x 
xx.x 
   80% Confidence Interval for Geometric Means[2] 
xx.xx, xx.xx 
xx.xx, xx.xx 
 
   95% Confidence Interval for Geometric Means[2] 
xx.xx, xx.xx 
xx.xx, xx.xx 
 
   80% Confidence Interval for Geometric Means Difference[2] 
 
 
xx.xx, xx.xx 
   95% Confidence Interval for Geometric Means Difference[2] 
 
 
xx.xx, xx.xx 
 
 
 
 
Note: The endpoint is the ratio between the Ki-67 measurements obtained from Surgery visit and baseline, which will be 
derived as = exp(log(Ki-67 at Surgery) - log(Ki-67 at baseline)). 
[1] Analysis based on an analysis of covariance (ANCOVA) model with baseline Ki-67 score (assessed centrally: <20% vs 
≥20%), the tumor size (≤2 cm, >2 to <5 cm, or ≥5 cm) as covariates for treatment. Baseline Ki-67 score and/or the tumor 
size categories are derived based on data collected instead of data reported in IRT. 
[2] Back transformed values of [1]. 
Source: Listing 16.2.6.1. 


Arvinas Estrogen Receptor, Inc (Arvinas) 
 
 
CONFIDENTIAL 
ARV-471-BC-201 
 
<Final 2.0> 
<date> / <time> / <program name> 
 
Page xxx of yyy 
 
47 
Programming Note:  
Table 14.2.1.3.2 
Summary of Ki-67 Percentage Change from Baseline at Surgery with Local Ki-67 as a Covariate 
Analysis Set: Full Analysis Set 
 
                              
ARV-471 
200 mg N=XXX 
 Anastrozole  
1 mg N=XX 
Difference 
log(Ki-67 at baseline)  
 
 
 
   n 
xxx 
xx 
 
   Mean (Standard Deviation) 
xx.x(xx.xx) 
xx.x(xx.xx) 
 
   Median 
xx.x 
xx.x 
 
   Min, Max 
xx, xx 
xx, xx 
 
 
 
 
 
log(Ki-67 at Surgery) 
 
 
 
   n 
xxx 
xx 
 
   Mean (Standard Deviation) 
xx.x(xx.xx) 
xx.x(xx.xx) 
 
   Median 
xx.x 
xx.x 
 
   Min, Max 
xx, xx 
xx, xx 
 
 
 
 
 
log(Ki-67 at Surgery) - log(Ki-67 at baseline) 
 
 
 
   n 
xxx 
xx 
 
   Mean (Standard Deviation) 
xx.x(xx.xx) 
xx.x(xx.xx) 
 
   Median 
xx.x 
xx.x 
 
   Min, Max 
xx, xx 
xx, xx 
 
   LSM (Standard Error)[1]  
xx.x(xx.xx) 
xx.x(xx.xx) 
xx.x(xx.xx) 
   80% Confidence Interval for LSM[1] 
xx.xx, xx.xx 
xx.xx, xx.xx 
 
   95% Confidence Interval for LSM[1] 
xx.xx, xx.xx 
xx.xx, xx.xx 
 
   80% Confidence Interval for LSM Difference[1] 
 
 
xx.xx, xx.xx 
   95% Confidence Interval for LSM Difference[1] 
 
 
xx.xx, xx.xx 
 
 
 
 
Ratio between Ki-67 at Surgery and Ki-67 at baseline 
 
 
 
   Geometric Means[2] 
xx.x 
xx.x 
xx.x 
   80% Confidence Interval for Geometric Means[2] 
xx.xx, xx.xx 
xx.xx, xx.xx 
 
   95% Confidence Interval for Geometric Means[2] 
xx.xx, xx.xx 
xx.xx, xx.xx 
 
   80% Confidence Interval for Geometric Means Difference[2] 
 
 
xx.xx, xx.xx 
   95% Confidence Interval for Geometric Means Difference[2] 
 
 
xx.xx, xx.xx 
 
 
 
 
Note: The endpoint is the ratio between the Ki-67 measurements obtained from Surgery visit and baseline, which will be 
derived as = exp(log(Ki-67 at Surgery) - log(Ki-67 at baseline)). 
[1] Analysis based on an analysis of covariance (ANCOVA) model with baseline Ki-67 score (assessed locally: <20% vs 
≥20%), the tumor size (≤2 cm, >2 to <5 cm, or ≥5 cm) as covariates for treatment. Baseline Ki-67 score and/or the tumor 
size categories are derived based on data collected instead of data reported in IRT. 
[2] Back transformed values of [1]. 
Source: Listing 16.2.6.1. 


Arvinas Estrogen Receptor, Inc (Arvinas) 
 
 
CONFIDENTIAL 
ARV-471-BC-201 
 
<Final 2.0> 
<date> / <time> / <program name> 
 
Page xxx of yyy 
 
48 
Programming Note:  
Table 14.2.1.3.3 
Summary of Ki-67 Percentage Change from Baseline at Surgery without Covariate 
Analysis Set: Full Analysis Set 
 
                              
ARV-471 
200 mg N=XXX 
 Anastrozole  
1 mg N=XX 
Difference 
log(Ki-67 at baseline)  
 
 
 
   n 
xxx 
xx 
 
   Mean (Standard Deviation) 
xx.x(xx.xx) 
xx.x(xx.xx) 
 
   Median 
xx.x 
xx.x 
 
   Min, Max 
xx, xx 
xx, xx 
 
 
 
 
 
log(Ki-67 at Surgery) 
 
 
 
   n 
xxx 
xx 
 
   Mean (Standard Deviation) 
xx.x(xx.xx) 
xx.x(xx.xx) 
 
   Median 
xx.x 
xx.x 
 
   Min, Max 
xx, xx 
xx, xx 
 
 
 
 
 
log(Ki-67 at Surgery) - log(Ki-67 at baseline) 
 
 
 
   n 
xxx 
xx 
 
   Mean (Standard Deviation) 
xx.x(xx.xx) 
xx.x(xx.xx) 
 
   Median 
xx.x 
xx.x 
 
   Min, Max 
xx, xx 
xx, xx 
 
   LSM (Standard Error)[1]  
xx.x(xx.xx) 
xx.x(xx.xx) 
xx.x(xx.xx) 
   80% Confidence Interval for LSM[1] 
xx.xx, xx.xx 
xx.xx, xx.xx 
 
   95% Confidence Interval for LSM[1] 
xx.xx, xx.xx 
xx.xx, xx.xx 
 
   80% Confidence Interval for LSM Difference[1] 
 
 
xx.xx, xx.xx 
   95% Confidence Interval for LSM Difference[1] 
 
 
xx.xx, xx.xx 
 
 
 
 
Ratio between Ki-67 at Surgery and Ki-67 at baseline 
 
 
 
   Geometric Means[2] 
xx.x 
xx.x 
xx.x 
   80% Confidence Interval for Geometric Means[2] 
xx.xx, xx.xx 
xx.xx, xx.xx 
 
   95% Confidence Interval for Geometric Means[2] 
xx.xx, xx.xx 
xx.xx, xx.xx 
 
   80% Confidence Interval for Geometric Means Difference[2] 
 
 
xx.xx, xx.xx 
   95% Confidence Interval for Geometric Means Difference[2] 
 
 
xx.xx, xx.xx 
 
 
 
 
Note: The endpoint is the ratio between the Ki-67 measurements obtained from Surgery visit and baseline, which will be 
derived as = exp(log(Ki-67 at Surgery) - log(Ki-67 at baseline)). 
[1] Analysis based on an analysis of variance (ANOVA) model. 
[2] Back transformed values of [1]. 
Source: Listing 16.2.6.1. 


Arvinas Estrogen Receptor, Inc (Arvinas) 
 
 
CONFIDENTIAL 
ARV-471-BC-201 
 
<Final 2.0> 
<date> / <time> / <program name> 
 
Page xxx of yyy 
 
49 
Table 14.2.1.4.1 
Summary of Ki-67 Percentage Change from Baseline at Surgery – Subgroup Analysis by Tumor Size   
Analysis Set: Full Analysis Set  
Tumor Size: ≤2 cm   
 
ARV-471 
200 mg N=XXX 
 Anastrozole  
1 mg N=XX 
Difference 
log(Ki-67 at baseline) 
 
 
 
   n 
xxx 
xx 
 
   Mean (Standard Deviation) 
xx.x(xx.xx) 
xx.x(xx.xx) 
 
   Median 
xx.x 
xx.x 
 
   Min, Max 
xx, xx 
xx, xx 
 
 
 
 
 
log(Ki-67 at Surgery 
 
 
 
   n) 
xxx 
xx 
 
   Mean (Standard Deviation) 
xx.x(xx.xx) 
xx.x(xx.xx) 
 
   Median 
xx.x 
xx.x 
 
   Min, Max 
xx, xx 
xx, xx 
 
 
 
 
 
log(Ki-67 at Surgery) - log(Ki-67 at baseline) 
 
 
 
   n 
xxx 
xx 
 
   Mean (Standard Deviation) 
xx.x(xx.xx) 
xx.x(xx.xx) 
 
   Median 
xx.x 
xx.x 
 
   Min, Max 
xx, xx 
xx, xx 
 
   LSM (Standard Error)[1] 
xx.x(xx.xx) 
xx.x(xx.xx) 
xx.x(xx.xx) 
   80% Confidence Interval for LSM[1] 
xx.xx, xx.xx 
xx.xx, xx.xx 
 
   95% Confidence Interval for LSM[1] 
xx.xx, xx.xx 
xx.xx, xx.xx 
 
   80% Confidence Interval for LSM Difference[1] 
 
 
xx.xx, xx.xx 
   95% Confidence Interval for LSM Difference[1] 
 
 
xx.xx, xx.xx 
 
 
 
 
Ratio between Ki-67 at Surgery and Ki-67 at baseline 
 
 
 
   Geometric Means[2] 
xx.x 
xx.x 
xx.x 
   80% Confidence Interval for Geometric Means[2] 
xx.xx, xx.xx 
xx.xx, xx.xx 
 
   95% Confidence Interval for Geometric Means[2] 
xx.xx, xx.xx 
xx.xx, xx.xx 
 
   80% Confidence Interval for Geometric Means Difference[2] 
 
 
xx.xx, xx.xx 
   95% Confidence Interval for Geometric Means Difference[2] 
 
 
xx.xx, xx.xx 
 
 
 
 
Note: The endpoint is the ratio between the Ki-67 measurements obtained from Surgery visit and baseline, which will be 
derived as = exp(log(Ki-67 at Surgery) - log(Ki-67 at baseline)). 
Note: Baseline tumor size categories are derived based on data collected instead of data reported in IRT. 
[1] Analysis based on an analysis of variance (ANOVA) model. 
[2] Back transformed values of [1]. 
Source: Listing 16.2.6.1. 
Programming Note:  


Arvinas Estrogen Receptor, Inc (Arvinas) 
 
 
CONFIDENTIAL 
ARV-471-BC-201 
 
<Final 2.0> 
<date> / <time> / <program name> 
 
Page xxx of yyy 
 
50 
Repeat the table for ‘Tumor Size: >2 to <5 cm’, and ‘Tumor Size: ≥5 cm’ on new page. 


Arvinas Estrogen Receptor, Inc (Arvinas) 
 
 
CONFIDENTIAL 
ARV-471-BC-201 
 
<Final 2.0> 
<date> / <time> / <program name> 
 
Page xxx of yyy 
 
51 
Table 14.2.1.4.2 
Summary of Ki-67 Percentage Change from Baseline at Surgery – Subgroup Analysis by Local Ki-67 Baseline Score  
Analysis Set: Full Analysis Set  
Local Ki-67 Baseline Score: < 20%  
 
ARV-471 
200 mg N=XXX 
Anastrozole  
1 mg N=XX 
Difference 
log(Ki-67 at baseline) 
 
 
 
   n 
xxx 
xx 
 
   Mean (Standard Deviation) 
xx.x(xx.xx) 
xx.x(xx.xx) 
 
   Median 
xx.x 
xx.x 
 
   Min, Max 
xx, xx 
xx, xx 
 
 
 
 
 
log(Ki-67 at Surgery 
 
 
 
   n) 
xxx 
xx 
 
   Mean (Standard Deviation) 
xx.x(xx.xx) 
xx.x(xx.xx) 
 
   Median 
xx.x 
xx.x 
 
   Min, Max 
xx, xx 
xx, xx 
 
 
 
 
 
log(Ki-67 at Surgery) - log(Ki-67 at baseline) 
 
 
 
   n  
xxx 
xx 
 
   Mean (Standard Deviation) 
xx.x(xx.xx) 
xx.x(xx.xx) 
 
   Median 
xx.x 
xx.x 
 
   Min, Max 
xx, xx 
xx, xx 
 
   LSM (Standard Error)[1] 
xx.x(xx.xx) 
xx.x(xx.xx) 
xx.x(xx.xx) 
   80% Confidence Interval for LSM[1] 
xx.xx, xx.xx 
xx.xx, xx.xx 
 
   95% Confidence Interval for LSM[1] 
xx.xx, xx.xx 
xx.xx, xx.xx 
 
   80% Confidence Interval for LSM Difference[1] 
 
 
xx.xx, xx.xx 
   95% Confidence Interval for LSM Difference[1] 
 
 
xx.xx, xx.xx 
 
 
 
 
Ratio between Ki-67 at Surgery and Ki-67 at baseline 
 
 
 
   Geometric Means[2] 
xx.x 
xx.x 
xx.x 
   80% Confidence Interval for Geometric Means[2] 
xx.xx, xx.xx 
xx.xx, xx.xx 
 
   95% Confidence Interval for Geometric Means[2] 
xx.xx, xx.xx 
xx.xx, xx.xx 
 
   80% Confidence Interval for Geometric Means Difference[2] 
 
 
xx.xx, xx.xx 
   95% Confidence Interval for Geometric Means Difference[2] 
 
 
xx.xx, xx.xx 
 
 
 
 
Note: The endpoint is the ratio between the Ki-67 measurements obtained from Surgery visit and baseline, which will be 
derived as = exp(log(Ki-67 at Surgery) - log(Ki-67 at baseline)). 
Note: Baseline Ki-67 score are derived based on data collected instead of data reported in IRT. 
[1] Analysis based on an analysis of variance (ANOVA) model. 
[2] Back transformed values of [1]. 
Source: Listing 16.2.6.1. 
Programming Note:  


Arvinas Estrogen Receptor, Inc (Arvinas) 
 
 
CONFIDENTIAL 
ARV-471-BC-201 
 
<Final 2.0> 
<date> / <time> / <program name> 
 
Page xxx of yyy 
 
52 
Repeat the table for ‘Local Ki-67 Baseline Score: ≥ 20%” on new page. 
 
 


Arvinas Estrogen Receptor, Inc (Arvinas) 
 
 
CONFIDENTIAL 
ARV-471-BC-201 
 
<Final 2.0> 
<date> / <time> / <program name> 
 
Page xxx of yyy 
 
53 
Table 14.2.1.4.3 
Summary of Ki-67 Percentage Change from Baseline at Surgery – Subgroup Analysis by Central Ki-67 Baseline Score  
Analysis Set: Full Analysis Set  
Central Ki-67 Baseline Score: < 20%  
 
ARV-471 
200 mg N=XXX 
 Anastrozole  
1 mg N=XX 
Difference 
log(Ki-67 at baseline)  
 
 
 
   n 
xxx 
xx 
 
   Mean (Standard Deviation) 
xx.x(xx.xx) 
xx.x(xx.xx) 
 
   Median 
xx.x 
xx.x 
 
   Min, Max 
xx, xx 
xx, xx 
 
 
 
 
 
log(Ki-67 at Surgery) 
 
 
 
   n 
xxx 
xx 
 
   Mean (Standard Deviation) 
xx.x(xx.xx) 
xx.x(xx.xx) 
 
   Median 
xx.x 
xx.x 
 
   Min, Max 
xx, xx 
xx, xx 
 
 
 
 
 
log(Ki-67 at Surgery) - log(Ki-67 at baseline) 
 
 
 
   n 
xxx 
xx 
 
   Mean (Standard Deviation) 
xx.x(xx.xx) 
xx.x(xx.xx) 
 
   Median 
xx.x 
xx.x 
 
   Min, Max 
xx, xx 
xx, xx 
 
   LSM (Standard Error)[1] 
xx.x(xx.xx) 
xx.x(xx.xx) 
xx.x(xx.xx) 
   80% Confidence Interval for LSM[1] 
xx.xx, xx.xx 
xx.xx, xx.xx 
 
   95% Confidence Interval for LSM[1] 
xx.xx, xx.xx 
xx.xx, xx.xx 
 
   80% Confidence Interval for LSM Difference[1] 
 
 
xx.xx, xx.xx 
   95% Confidence Interval for LSM Difference[1] 
 
 
xx.xx, xx.xx 
 
 
 
 
Ratio between Ki-67 at Surgery and Ki-67 at baseline 
 
 
 
   Geometric Means[2] 
xx.x 
xx.x 
xx.x 
   80% Confidence Interval for Geometric Means[2] 
xx.xx, xx.xx 
xx.xx, xx.xx 
 
   95% Confidence Interval for Geometric Means[2] 
xx.xx, xx.xx 
xx.xx, xx.xx 
 
   80% Confidence Interval for Geometric Means Difference[2] 
 
 
xx.xx, xx.xx 
   95% Confidence Interval for Geometric Means Difference[2] 
 
 
xx.xx, xx.xx 
 
 
 
 
Note: The endpoint is the ratio between the Ki-67 measurements obtained from Surgery visit and baseline, which will be 
derived as = exp(log(Ki-67 at Surgery) - log(Ki-67 at baseline)). 
Note: Baseline Ki-67 score are derived based on data collected instead of data reported in IRT. 
[1] Analysis based on an analysis of variance (ANOVA) model. 
[2] Back transformed values of [1]. 
Source: Listing 16.2.6.1. 
Programming Note:  


Arvinas Estrogen Receptor, Inc (Arvinas) 
 
 
CONFIDENTIAL 
ARV-471-BC-201 
 
<Final 2.0> 
<date> / <time> / <program name> 
 
Page xxx of yyy 
 
54 
Repeat the table for ‘Central Ki-67 Baseline Score: ≥ 20%” on new page. 
 
 


Arvinas Estrogen Receptor, Inc (Arvinas) 
 
 
CONFIDENTIAL 
ARV-471-BC-201 
 
<Final 2.0> 
<date> / <time> / <program name> 
 
Page xxx of yyy 
 
55 
Table 14.2.1.5.1 
Summary of Concordance Ki-67 Baseline Score between Central and Local Laboratories 
Analysis Set: Ki-67 Evaluable Set            
 
Local Ki-67 Baseline 
 Score <20% 
Local Ki-67 Baseline 
 Score ≥20% 
Total 
ARV-471 200 mg (N=XXX), n(%)  
 
 
 
   Central Ki-67 Baseline Score <20%  
XXX(XX.X) 
XXX(XX.X) 
XXX(XX.X) 
   Central Ki-67 Baseline Score ≥20% 
XXX(XX.X) 
XXX(XX.X) 
XXX(XX.X) 
   Total    
XXX(XX.X) 
XXX(XX.X) 
XXX(XX.X) 
 
 
 
 
Anastrozole 1 mg (N=XX), n(%) 
 
 
 
   Central Ki-67 Baseline Score <20% 
XX(XX.X) 
XX(XX.X) 
XX(XX.X) 
   Central Ki-67 Baseline Score ≥20% 
XX(XX.X) 
XX(XX.X) 
XX(XX.X) 
   Total 
XX(XX.X) 
XX(XX.X) 
XX(XX.X) 
 
 
 
 
Note: The percentage is based on N. 
Source: Listing 16.2.6.1. 
 


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Table 14.2.1.5.2 
Summary of Concordance Central/Local Ki-67 Baseline Score with Randomization Baseline Ki-67 Score 
Analysis Set: Ki-67 Evaluable Set                      
 
Randomization Baseline  
Ki-67 Score <20%  
Randomization Baseline  
Ki-67 Score ≥20% 
Total 
ARV-471 200 mg (N=XXX), n(%)   
 
 
 
   Central Ki-67 Baseline Score <20%  
XXX(XX.X) 
XXX(XX.X) 
XXX(XX.X) 
   Central Ki-67 Baseline Score ≥20% 
XXX(XX.X) 
XXX(XX.X) 
XXX(XX.X) 
   Total    
XXX(XX.X) 
XXX(XX.X) 
XXX(XX.X) 
 
 
 
 
ARV-471 200 mg (N=XXX), n(%) 
 
 
 
   Local Ki-67 Baseline Score <20%  
XXX(XX.X) 
XXX(XX.X) 
XXX(XX.X) 
   Local Ki-67 Baseline Score ≥20% 
XXX(XX.X) 
XXX(XX.X) 
XXX(XX.X) 
   Total    
XXX(XX.X) 
XXX(XX.X) 
XXX(XX.X) 
 
 
 
 
Anastrozole 1 mg (N=XX), n(%) 
 
 
 
   Central Ki-67 Baseline Score <20%  
XX(XX.X) 
XX(XX.X) 
XX(XX.X) 
   Central Ki-67 Baseline Score ≥20% 
XX(XX.X) 
XX(XX.X) 
XX(XX.X) 
   Total 
XX(XX.X) 
XX(XX.X) 
XX(XX.X) 
 
 
 
 
Anastrozole 1 mg (N=XX), n(%) 
 
 
 
   Local Ki-67 Baseline Score <20%  
XX(XX.X) 
XX(XX.X) 
XX(XX.X) 
   Local Ki-67 Baseline Score ≥20% 
XX(XX.X) 
XX(XX.X) 
XX(XX.X) 
   Total 
XX(XX.X) 
XX(XX.X) 
XX(XX.X) 
 
 
 
 
Note: The percentage is based on N. 
Source: Listing 16.2.6.1. 
 
 
 


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Table 14.2.1.5.3 
Summary of Concordance Acutal Primary Breast Tumor Size with Randomization Primary Breast Tumor Size 
Analysis Set: Ki-67 Evaluable Set                     
 
Randomization  
Primary Breast  
Tumor Size  
<=2 cm   
Randomization  
Primary Breast 
Tumor Size  
>2-<5 cm 
Randomization 
Primary Breast 
Tumor Size  
>2-<5 cm 
Total 
ARV-471200 mg (N=XXX), n(%) 
 
 
 
 
   Acutal Primary Breast Tumor Size <=2 cm  
XXX(XX.X) 
XXX(XX.X) 
XXX(XX.X) 
XXX(XX.X) 
   Acutal Primary Breast Tumor Size >2-<5 cm 
XXX(XX.X) 
XXX(XX.X) 
XXX(XX.X) 
XXX(XX.X) 
   Acutal Primary Breast Tumor Size >2-<5 cm 
XXX(XX.X) 
XXX(XX.X) 
XXX(XX.X) 
XXX(XX.X) 
   Total    
XXX(XX.X) 
XXX(XX.X) 
XXX(XX.X) 
XXX(XX.X) 
 
 
 
 
 
ARV-471200 mg (N=XXX), n(%) 
 
 
 
 
   Acutal Primary Breast Tumor Size <=2 cm  
XXX(XX.X) 
XXX(XX.X) 
XXX(XX.X) 
XXX(XX.X) 
   Acutal Primary Breast Tumor Size >2-<5 cm 
XXX(XX.X) 
XXX(XX.X) 
XXX(XX.X) 
XXX(XX.X) 
   Acutal Primary Breast Tumor Size >2-<5 cm 
XXX(XX.X) 
XXX(XX.X) 
XXX(XX.X) 
XXX(XX.X) 
   Total    
XXX(XX.X) 
XXX(XX.X) 
XXX(XX.X) 
XXX(XX.X) 
 
 
 
 
 
Note: The percentage is based on N. 
Source: Listing 16.2.6.1. 
 
 


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Table 14.2.2.1.1 
Summary of Post-Surgery Pathological Response and pCR Rate - Determined by Site Pathologist 
Analysis Set: Full Analysis Set  
 
ARV-471  
200 mg N=XXX 
Anastrozole  
1 mg N=XX 
Difference 
Participants Not Receiving Surgery, n(%) 
XXX(XX.X) 
XX(XX.X) 
 
Participants Receiving Unscheduled Surgery, n(%)    
XXX(XX.X) 
XX(XX.X) 
 
Post-Surgery Pathological Response in Participants 
Receiving Surgery at C6D18, n(%) 
 
 
 
   Pathological Complete Response (pCR) 
XXX(XX.X) 
XX(XX.X) 
 
   Pathological Partial Response (pPR) 
XXX(XX.X) 
XX(XX.X) 
 
   No Response (NR) 
XXX(XX.X) 
XX(XX.X) 
 
 
 
 
 
pCR Rate in Participants Receiving Surgery at C6D18, n(%) 
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
   80% Wilson confidence interval  
XX.X,XX.X 
XX.X,XX.X 
XX.X,XX.X  
   95% Wilson confidence interval  
XX.X,XX.X 
XX.X,XX.X 
XX.X,XX.X  
 
 
 
 
Note: pCR rate is the proportion of participants with pCR. 
Source: Listing 16.2.6.2. 
 
 
 
 
 
 


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Table 14.2.2.1.2 
Summary of Post-Surgery Pathological Response and pCR Rate – Calculated  
Analysis Set: Full Analysis Set  
 
ARV-471  
200 mg N=XXX 
Anastrozole  
1 mg N=XX 
Difference 
Participants Not Receiving Surgery, n(%) 
XXX(XX.X) 
XX(XX.X) 
 
Participants Receiving Unscheduled Surgery, n(%)    
XXX(XX.X) 
XX(XX.X) 
 
Post-Surgery Pathological Response in Participants Receiving Surgery at 
C6D18, n(%) 
 
 
 
   Calculated Pathological Complete Response (pCR) 
XXX(XX.X) 
XX(XX.X) 
 
   Non pCR  
XXX(XX.X) 
XX(XX.X) 
 
 
 
 
 
pCR Rate in Participants Receiving Surgery at C6D18, n(%) 
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
    80% Wilson confidence interval  
XX.X,XX.X 
XX.X,XX.X 
XX.X,XX.X  
    95% Wilson confidence interval  
XX.X,XX.X 
XX.X,XX.X 
XX.X,XX.X  
 
 
 
 
Note: pCR is programmatically derived according to the definition in the protocol using Disease Staging – Post-Surgery 
data: pCR is defined as no invasive cancer in the breast and sampled axillary lymph nodes following completion of 
neoadjuvant systemic therapy (Pathologic Tumor - ypT = ypT0 or ypTis, and Pathologic Lymph Nodes – ypN = ypN0).pCR rate 
is the proportion of participants with pCR. 
Source: Listing 16.2.6.2. 
 
 
 
 
 


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Table 14.2.2.1.3.1 
Summary of Post-Surgery Disease Staging 
Analysis Set: Full Analysis Set  
 
ARV-471 
200 mg N=XXX 
 Anastrozole  
1 mg N=XX 
Total 
N=XXX 
Participants Not Receiving Surgery, n(%) 
XXX(XX.X) 
XX(XX.X) 
XX(XX.X) 
Participants Receiving Unscheduled Surgery, n(%)    
XXX(XX.X) 
XX(XX.X) 
XX(XX.X) 
Pathologic Tumor - ypT in Participants Receiving Surgery at 
C6D18, n(%) 
 
 
 
   ypTx  
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
   ypT0 
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
   ypTis 
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
   ypT1mi 
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
   ypT1a 
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
   ypT1b 
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
   ypT1c 
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
   ypT2 
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
   ypT3 
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
   ypT4a 
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
   ypT4b 
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
   ypT4c 
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
 
 
 
 
Multiple Foci of Residual Tumor? in Participants Receiving 
Surgery at C6D18, n(%) 
 
 
 
   Yes 
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
   No  
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
 
 
 
 
Pathologic Lymph Nodes – ypN in Participants Receiving 
Surgery at C6D18, n(%) 
 
 
 
   ypNX  
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
   ypN0 
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
   ypN0(i+) 
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
   ypN0(mol+) 
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
   ypN1 
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
   ypN1mi 
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
   ypN1a 
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
   ypN1b 
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
   ypN1c 
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
   ypN2 
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
   ypN2a 
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
   ypN2b 
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
   ypN3 
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
   ypN3a 
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
   ypN3b 
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
   ypN3c 
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 


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Distant Metastasis (M) in Participants Receiving Surgery at 
C6D18, n(%) 
 
 
 
   M0  
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
   pM1 
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
   Unknown 
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
 
 
 
 
Lymphatic Vascular Invasion Classification in Participants 
Receiving Surgery at C6D18, n(%) 
 
 
 
   Present  
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
   Not Present 
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
   Unknown 
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
 
 
 
 
Source: Listing 16.2.6.8. 
Date of data extraction: DDMMMYYYY; Date of Creation: DDMMMYYYY. 
 
 
 
Repeat the following table with Table 14.2.2.1.3.1 shell 
Table 14.2.2.1.3.2 
Summary of Post-Surgery Disease Staging 
Analysis Set: Ki-67 Evaluable Set  
 


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Table 14.2.2.2 
Summary of Modified Pre-operative Endocrine Prognostic Index (mPEPI) Score and mPEPI 0 Rate  
Analysis Set: Full Analysis Set  
 
ARV-471 
200 mg N=XXX  
Anastrozole  
1 mg N=XX 
Difference 
Participants Not Assessed at C6D18, n(%) 
XXX(XX.X) 
XX(XX.X) 
 
 
 
 
 
(mPEPI) Score at at C6D18, n(%) 
 
 
 
   0 
XXX(XX.X) 
XX(XX.X) 
 
   1~2 
XXX(XX.X) 
XX(XX.X) 
 
   3 
XXX(XX.X) 
XX(XX.X) 
 
   >3 
XXX(XX.X) 
XX(XX.X) 
 
 
 
 
 
mPEPI 0 Rate, n(%) 
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
   80% Wilson confidence interval 
XX.X,XX.X 
XX.X,XX.X 
XX.X,XX.X 
   95% Wilson confidence interval 
XX.X,XX.X 
XX.X,XX.X 
XX.X,XX.X 
 
 
 
 
Odds Ratio of mPEPI0 Rate [1] 
XX.XX 
 
 
   80% confidence interval [1] 
XX.XX,XX.XX 
 
 
   95% confidence interval [1] 
XX.XX,XX.XX 
 
 
 
 
 
 
Odds Ratio of mPEPI0 Rate [2] 
XX.XX 
 
 
   80% confidence interval [2] 
XX.XX,XX.XX 
 
 
   95% confidence interval [2] 
XX.XX,XX.XX 
 
 
 
 
 
 
Note: mPEPI0 rate is the proportion of participants achieving 0 for total mPEPI after treatment (before surgery). 
[1] Analysis based on Cochran-Mantel-Haenszel method adjusted for the stratification factors, including baseline Ki-67 
score (assessed centrally: <20% vs ≥20%) and tumor size (≤2 cm, >2 to <5 cm, or ≥5 cm). Baseline Ki-67 score and/or the 
tumor size categories are derived based on data collected instead of data reported in IRT. 
[2] Analysis based on Cochran-Mantel-Haenszel method adjusted for the stratification factors, including baseline Ki-67 
score (assessed locally: <20% vs ≥20%) and tumor size (≤2 cm, >2 to <5 cm, or ≥5 cm). Baseline Ki-67 score and/or the 
tumor size categories are derived based on data collected instead of data reported in IRT. 
Source: Listing 16.2.6.1. 
 
 


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Table 14.2.2.3 
Summary of Breast Conserving Surgery (BCS) and BCS Rate  
Analysis Set: Full Analysis Set  
 
ARV-471   
200 mg N=XXX 
Anastrozole  
1 mg N=XX 
Difference 
Participants Not Receiving Surgery, n(%) 
XXX(XX.X) 
XX(XX.X) 
 
Participants Receiving Unscheduled Surgery, n(%)    
XXX(XX.X) 
XX(XX.X) 
 
Participants Receiving Mastectomy at C6D18, n(%) 
XXX(XX.X) 
XX(XX.X) 
 
Participants Receiving Breast Conserving Surgery at C6D18, n(%) 
XXX(XX.X) 
XX(XX.X) 
 
 
 
 
 
BCS Rate in Participants Receiving Breast Conserving Surgery at 
C6D18, n(%) 
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
   80% Wilson confidence interval 
XX.X,XX.X 
XX.X,XX.X 
XX.X,XX.X 
   95% Wilson confidence interval 
XX.X,XX.X 
XX.X,XX.X 
XX.X,XX.X 
 
 
 
 
Note: Breast conserving surgery (BCS) Rate is the proportion of participants receiving breast conserving surgery. 
Source: Listing 16.2.6.2. 
 
 
 


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Table 14.2.2.4 
Summary of Radiographic Response per mRECIST during Cycle 6 
Analysis Set: Full Analysis Set       
 
ARV-471 
200 mg N=XXX 
Anastrozole  
1 mg N=XX 
Radiographic Response per mRECIST during Cycle 6, n(%) 
 
 
   Complete response (CR) 
XXX(XX.X) 
XX(XX.X) 
   Partial response (PR) 
XXX(XX.X) 
XX(XX.X) 
   Stable disease (SD) 
XXX(XX.X) 
XX(XX.X) 
   Progressive disease (PD) 
XXX(XX.X) 
XX(XX.X) 
   Not evaluable (NE) 
XXX(XX.X) 
XX(XX.X) 
 
 
 
Note: Participants without disease assessment is categorized as Not evaluable. 
Source: Listing 16.4.6.1.  
 
 
 


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Table 14.2.2.5.1 
Summary of Complete Cycle Cell Arrest (CCCA) and CCCA Rate  
Analysis Set: Full Analysis Set  
 
ARV-471 
200 mg N=XXX 
Anastrozole  
1 mg N=XX 
Difference 
Complete Cycle Cell Arrest at Week 2, n(%) 
 
 
 
   No 
XXX(XX.X) 
XX(XX.X) 
 
   Yes 
XXX(XX.X) 
XX(XX.X) 
 
 
 
 
 
   CCCA Rate, n(%) 
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
      80% Wilson confidence interval 
XX.X,XX.X 
XX.X,XX.X 
XX.X,XX.X 
      95% Wilson confidence interval 
XX.X,XX.X 
XX.X,XX.X 
XX.X,XX.X 
   Odds Ratio of CCCA Rate [1] 
XX.XX 
 
 
      80% confidence interval [1] 
XX.XX,XX.XX 
 
 
      95% confidence interval [1] 
XX.XX,XX.XX 
 
 
   Odds Ratio of CCCA Rate [2] 
XX.XX 
 
 
      80% confidence interval [2] 
XX.XX,XX.XX 
 
 
      95% confidence interval [2] 
XX.XX,XX.XX 
 
 
 
 
 
 
Participants Not Receiving Surgery, n(%) 
XXX(XX.X) 
XX(XX.X) 
 
Participants Receiving Unscheduled Surgery, n(%)    
XXX(XX.X) 
XX(XX.X) 
 
Complete Cycle Cell Arrest at C6D18 Surgery, n(%) 
 
 
 
   No 
XXX(XX.X) 
XX(XX.X) 
 
   Yes 
XXX(XX.X) 
XX(XX.X) 
 
 
 
 
 
   CCCA Rate, n(%) 
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
      80% Wilson confidence interval 
XX.X,XX.X 
XX.X,XX.X 
XX.X,XX.X 
      95% Wilson confidence interval 
XX.X,XX.X 
XX.X,XX.X 
XX.X,XX.X 
   Odds Ratio of CCCA Rate [1] 
XX.XX 
 
 
      80% confidence interval [1] 
XX.XX,XX.XX 
 
 
      95% confidence interval [1] 
XX.XX,XX.XX 
 
 
   Odds Ratio of CCCA Rate [2] 
XX.XX 
 
 
      80% confidence interval [2] 
XX.XX,XX.XX 
 
 
      95% confidence interval [2] 
XX.XX,XX.XX 
 
 
 
 
 
 
Note: Complete cycle cell arrest (CCCA) at Week 2/surgery is defined as Ki67 score ≤ 2.7%. CCCA rate is the proportion 
of participants achieving CCCA) at Week 2 (or C1D15)/surgery. 
[1] Analysis based on Cochran-Mantel-Haenszel method adjusted for the stratification factors, including baseline Ki-67 
score (assessed centrally: <20% vs ≥20%) and tumor size (≤2 cm, >2 to <5 cm, or ≥5 cm). Baseline Ki-67 score and/or the 
tumor size categories are derived based on data collected instead of data reported in IRT. 
[2] Analysis based on Cochran-Mantel-Haenszel method adjusted for the stratification factors, including baseline Ki-67 
score (assessed locally: <20% vs ≥20%) and tumor size (≤2 cm, >2 to <5 cm, or ≥5 cm). Baseline Ki-67 score and/or the 
tumor size categories are derived based on data collected instead of data reported in IRT. 


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Source: Listing 16.2.6.2.  
 
 


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Table 14.2.2.5.2 
Summary of Complete Cycle Cell Arrest (CCCA) and CCCA Rate – Subgroup Analysis by Central Ki-67 Baseline Score 
Analysis Set: Full Analysis Set  
 Central Ki-67 Baseline Score: < 5% 
 
 
ARV-471 
200 mg N=XXX 
Anastrozole  
1 mg N=XX 
Difference 
Complete Cycle Cell Arrest at Week 2, n(%) 
XXX(XX.X) 
XX(XX.X) 
 
   No 
XXX(XX.X) 
XX(XX.X) 
 
   Yes 
XXX(XX.X) 
XX(XX.X) 
 
 
 
 
 
   CCCA Rate, n(%) 
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
      80% Wilson confidence interval 
XX.X,XX.X 
XX.X,XX.X 
XX.X,XX.X 
      95% Wilson confidence interval 
XX.X,XX.X 
XX.X,XX.X 
XX.X,XX.X 
   Odds Ratio of CCCA Rate [1] 
XX.XX 
 
 
      80% confidence interval [1] 
XX.XX,XX.XX 
 
 
      95% confidence interval [1] 
XX.XX,XX.XX 
 
 
   Odds Ratio of CCCA Rate [2] 
XX.XX 
 
 
      80% confidence interval [2] 
XX.XX,XX.XX 
 
 
      95% confidence interval [2] 
XX.XX,XX.XX 
 
 
 
 
 
 
Participants Not Receiving Surgery, n(%) 
XXX(XX.X) 
XX(XX.X) 
 
Participants Receiving Unscheduled Surgery, n(%)    
XXX(XX.X) 
XX(XX.X) 
 
Complete Cycle Cell Arrest at C6D18 Surgery, n(%) 
XXX(XX.X) 
XX(XX.X) 
 
   No 
XXX(XX.X) 
XX(XX.X) 
 
   Yes 
XXX(XX.X) 
XX(XX.X) 
 
 
 
 
 
   CCCA Rate, n(%) 
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
      80% Wilson confidence interval 
XX.X,XX.X 
XX.X,XX.X 
XX.X,XX.X 
      95% Wilson confidence interval 
XX.X,XX.X 
XX.X,XX.X 
XX.X,XX.X 
   Odds Ratio of CCCA Rate [1] 
XX.XX 
 
 
      80% confidence interval [1] 
XX.XX,XX.XX 
 
 
      95% confidence interval [1] 
XX.XX,XX.XX 
 
 
   Odds Ratio of CCCA Rate [2] 
XX.XX 
 
 
      80% confidence interval [2] 
XX.XX,XX.XX 
 
 
      95% confidence interval [2] 
XX.XX,XX.XX 
 
 
 
 
 
 
Note: Complete cycle cell arrest (CCCA) at Week 2/surgery is defined as Ki67 score ≤ 2.7%. CCCA rate is the proportion 
of participants achieving CCCA at Week 2 (or C1D15)/surgery. 
[1] Analysis based on Cochran-Mantel-Haenszel method adjusted for the stratification factors, including baseline Ki-67 
score (assessed centrally: <20% vs ≥20%) and tumor size (≤2 cm, >2 to <5 cm, or ≥5 cm). Baseline Ki-67 score and/or the 
tumor size categories are derived based on data collected instead of data reported in IRT. 
[2] Analysis based on Cochran-Mantel-Haenszel method adjusted for the stratification factors, including baseline Ki-67 
score (assessed locally: <20% vs ≥20%) and tumor size (≤2 cm, >2 to <5 cm, or ≥5 cm). Baseline Ki-67 score and/or the 
tumor size categories are derived based on data collected instead of data reported in IRT. 


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Source: Listing 16.2.6.2.  
Programming Note:  
Repeat the table for ‘Central Ki-67 Baseline Score: ≥ 5%” on new page. 
 














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Table 14.2.4.1.1 
Summary of ER AQUA Score Percentage Change at C1D15 from Baseline Value 
Analysis Set: Full Analysis Set  
 
ARV-471  
200 mg N=XXX 
Anastrozole  
1 mg N=XX 
Difference 
ER AQUA score at baseline  
 
 
 
   n  
xxx 
xx 
 
   Mean (Standard Deviation) 
xx.x(xx.xx) 
xx.x(xx.xx) 
 
   Median 
xx.x 
xx.x 
 
   Min, Max 
xx, xx 
xx, xx 
 
 
 
 
 
ER AQUA score at C1D15 
 
 
 
   n 
xxx 
xx 
 
   Mean (Standard Deviation) 
xx.x(xx.xx) 
xx.x(xx.xx) 
 
   Median 
xx.x 
xx.x 
 
   Min, Max 
xx, xx 
xx, xx 
 
 
 
 
 
ER AQUA score percentage change at C1D15 
 
 
 
   n 
xxx 
xx 
 
   Mean (Standard Deviation) 
xx.x(xx.xx) 
xx.x(xx.xx) 
 
   Median 
xx.x 
xx.x 
 
   Min, Max 
xx, xx 
xx, xx 
 
   LSM (Standard Error)[1] 
xx.x(xx.xx) 
xx.x(xx.xx) 
xx.x(xx.xx) 
   80% Confidence Interval for LSM[1] 
xx.xx, xx.xx 
xx.xx, xx.xx 
 
   95% Confidence Interval for LSM[1] 
xx.xx, xx.xx 
xx.xx, xx.xx 
 
   80% Confidence Interval for LSM Difference[1] 
 
 
xx.xx, xx.xx 
   95% Confidence Interval for LSM Difference[1] 
 
 
xx.xx, xx.xx 
 
 
 
 
Note: AQUA = absolute quantification score in arbitrary units. 
[1] Analysis based on an analysis of covariance (ANCOVA) model with baseline Ki-67 score (assessed centrally: <20% vs 
≥20%), the tumor size (≤2 cm, >2 to <5 cm, or ≥5 cm) as covariates for treatment. Baseline Ki-67 score and/or the tumor 
size categories are derived based on data collected instead of data reported in IRT. 
Source: Listing 16.2.6.2. 
Programming Note:  
 
 
 


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76 
Table 14.2.4.1.2 
Summary of ER AQUA Score Percentage Change at C1D15 from Baseline Value without Covariate   
Analysis Set: Full Analysis Set  
 
ARV-471 
200 mg N=XXX 
 Anastrozole  
1 mg N=XX 
Difference 
ER AQUA score at baseline 
 
 
 
   n 
xxx 
xx 
 
   Mean (Standard Deviation) 
xx.x(xx.xx) 
xx.x(xx.xx) 
 
   Median 
xx.x 
xx.x 
 
   Min, Max 
xx, xx 
xx, xx 
 
 
 
 
 
ER AQUA score at C1D15 
 
 
 
   n 
xxx 
xx 
 
   Mean (Standard Deviation) 
xx.x(xx.xx) 
xx.x(xx.xx) 
 
   Median 
xx.x 
xx.x 
 
   Min, Max 
xx, xx 
xx, xx 
 
 
 
 
 
ER AQUA score percentage change at C1D15 
 
 
 
   n 
xxx 
xx 
 
   Mean (Standard Deviation) 
xx.x(xx.xx) 
xx.x(xx.xx) 
 
   Median 
xx.x 
xx.x 
 
   Min, Max 
xx, xx 
xx, xx 
 
   LSM (Standard Error)[1] 
xx.x(xx.xx) 
xx.x(xx.xx) 
xx.x(xx.xx) 
   80% Confidence Interval for LSM[1] 
xx.xx, xx.xx 
xx.xx, xx.xx 
 
   95% Confidence Interval for LSM[1] 
xx.xx, xx.xx 
xx.xx, xx.xx 
 
   80% Confidence Interval for LSM Difference[1] 
 
 
xx.xx, xx.xx 
   95% Confidence Interval for LSM Difference[1] 
 
 
xx.xx, xx.xx 
 
 
 
 
 
 
 
 
Note: AQUA = absolute quantification score in arbitrary units. 
[1] Analysis based on an analysis of variance (ANOVA) model. 
Source: Listing 16.2.6.2. 
Programming Note:  
 
 
 


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77 
Table 14.2.4.1.3 
Summary of Log-Transformed ER AQUA Score Change at C1D15 from Baseline Value without Covariate   
Analysis Set: Full Analysis Set  
 
ARV-471 
200 mg N=XXX 
 Anastrozole  
1 mg N=XX 
Difference 
log(ER AQUA score at baseline)  
 
 
 
   n 
xxx 
xx 
 
   Mean (Standard Deviation) 
xx.x(xx.xx) 
xx.x(xx.xx) 
 
   Median 
xx.x 
xx.x 
 
   Min, Max 
xx, xx 
xx, xx 
 
 
 
 
 
log(ER AQUA score at C1D15)  
 
 
 
   n 
xxx 
xx 
 
   Mean (Standard Deviation) 
xx.x(xx.xx) 
xx.x(xx.xx) 
 
   Median 
xx.x 
xx.x 
 
   Min, Max 
xx, xx 
xx, xx 
 
 
 
 
 
log(ER AQUA score at C1D15) - log(ER AQUA score at baseline) 
 
 
 
   n 
xxx 
xx 
 
   Mean (Standard Deviation) 
xx.x(xx.xx) 
xx.x(xx.xx) 
 
   Median 
xx.x 
xx.x 
 
   Min, Max 
xx, xx 
xx, xx 
 
   LSM (Standard Error)[1]  
xx.x(xx.xx) 
xx.x(xx.xx) 
xx.x(xx.xx) 
   80% Confidence Interval for LSM[1] 
xx.xx, xx.xx 
xx.xx, xx.xx 
 
   95% Confidence Interval for LSM[1] 
xx.xx, xx.xx 
xx.xx, xx.xx 
 
   80% Confidence Interval for LSM Difference[1] 
 
 
xx.xx, xx.xx 
   95% Confidence Interval for LSM Difference[1] 
 
 
xx.xx, xx.xx 
 
 
 
 
Ratio between ER AQUA score at C1D15 and baseline 
 
 
 
 
   Geometric Means[2]  
xx.x 
xx.x 
xx.x 
   80% Confidence Interval for Geometric Means[2] 
xx.xx, xx.xx 
xx.xx, xx.xx 
 
   95% Confidence Interval for Geometric Means[2] 
xx.xx, xx.xx 
xx.xx, xx.xx  
 
   80% Confidence Interval for Geometric Means Difference[2] 
 
 
xx.xx, xx.xx 
   95% Confidence Interval for Geometric Means Difference[2] 
 
 
xx.xx, xx.xx 
 
 
 
 
 
 
 
 
Note: AQUA = absolute quantification score in arbitrary units. 
[1] Analysis based on an analysis of variance (ANOVA) model. 
[2] Back transformed values of [1]. 
Source: Listing 16.2.6.2. 
 
 


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78 
Table 14.2.4.2.1 
Summary of ER AQUA Score Percentage Change at Surgery from Baseline Value 
Analysis Set: Full Analysis Set  
 
  ARV-471   
200 mg N=XXX 
Anastrozole  
1 mg N=XX 
Difference 
ER AQUA score at baseline  
 
 
 
   n  
xxx 
xx 
 
   Mean (Standard Deviation) 
xx.x(xx.xx) 
xx.x(xx.xx) 
 
   Median 
xx.x 
xx.x 
 
   Min, Max 
xx, xx 
xx, xx 
 
 
 
 
 
ER AQUA score at surgery 
 
 
 
   n 
xxx 
xx 
 
   Mean (Standard Deviation) 
xx.x(xx.xx) 
xx.x(xx.xx) 
 
   Median 
xx.x 
xx.x 
 
   Min, Max 
xx, xx 
xx, xx 
 
 
 
 
 
ER AQUA score percentage change at surgery 
 
 
 
   n 
xxx 
xx 
 
   Mean (Standard Deviation) 
xx.x(xx.xx) 
xx.x(xx.xx) 
 
   Median 
xx.x 
xx.x 
 
   Min, Max 
xx, xx 
xx, xx 
 
   LSM (Standard Error)[1] 
xx.x(xx.xx) 
xx.x(xx.xx) 
xx.x(xx.xx) 
   80% Confidence Interval for LSM[1] 
xx.xx, xx.xx 
xx.xx, xx.xx 
 
   95% Confidence Interval for LSM[1] 
xx.xx, xx.xx 
xx.xx, xx.xx 
 
   80% Confidence Interval for LSM Difference[1] 
 
 
xx.xx, xx.xx 
   95% Confidence Interval for LSM Difference[1] 
 
 
xx.xx, xx.xx 
 
 
 
 
Note: AQUA = absolute quantification score in arbitrary units. 
[1] Analysis based on an analysis of covariance (ANCOVA) model with baseline Ki-67 score (assessed centrally: <20% vs  
≥20%), the tumor size (≤2 cm, >2 to <5 cm, or ≥5 cm) as covariates for treatment. Baseline Ki-67 score and/or the tumor 
size categories are derived based on data collected instead of data reported in IRT. 
Source: Listing 16.2.6.2. 
 
 


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79 
Table 14.2.4.2.2 
Summary of ER AQUA Score Percentage Change at Surgery from Baseline Value without Covariate   
Analysis Set: Full Analysis Set  
 
ARV-471 
200 mg N=XXX 
 Anastrozole  
1 mg N=XX 
Difference 
ER AQUA score at baseline 
 
 
 
   n 
xxx 
xx 
 
   Mean (Standard Deviation) 
xx.x(xx.xx) 
xx.x(xx.xx) 
 
   Median 
xx.x 
xx.x 
 
   Min, Max 
xx, xx 
xx, xx 
 
 
 
 
 
ER AQUA score at surgery 
 
 
 
   n 
xxx 
xx 
 
   Mean (Standard Deviation) 
xx.x(xx.xx) 
xx.x(xx.xx) 
 
   Median 
xx.x 
xx.x 
 
   Min, Max 
xx, xx 
xx, xx 
 
 
 
 
 
ER AQUA score percentage change at surgery 
 
 
 
   n 
xxx 
xx 
 
   Mean (Standard Deviation) 
xx.x(xx.xx) 
xx.x(xx.xx) 
 
   Median 
xx.x 
xx.x 
 
   Min, Max 
xx, xx 
xx, xx 
 
   LSM (Standard Error)[1] 
xx.x(xx.xx) 
xx.x(xx.xx) 
xx.x(xx.xx) 
   80% Confidence Interval for LSM[1] 
xx.xx, xx.xx 
xx.xx, xx.xx 
 
   95% Confidence Interval for LSM[1] 
xx.xx, xx.xx 
xx.xx, xx.xx 
 
   80% Confidence Interval for LSM Difference[1] 
 
 
xx.xx, xx.xx 
   95% Confidence Interval for LSM Difference[1] 
 
 
xx.xx, xx.xx 
 
 
 
 
 
 
 
 
Note: AQUA = absolute quantification score in arbitrary units. 
[1] Analysis based on an analysis of variance (ANOVA) model. 
Source: Listing 16.2.6.2. 
Programming Note:  
 
 
 


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80 
Table 14.2.4.2.3 
Summary of Log-Transformed ER AQUA Score Change at Surgery from Baseline Value without Covariate   
Analysis Set: Full Analysis Set  
 
ARV-471 
200 mg N=XXX 
 Anastrozole  
1 mg N=XX 
Difference 
log(ER AQUA score at baseline)  
 
 
 
   n 
xxx 
xx 
 
   Mean (Standard Deviation) 
xx.x(xx.xx) 
xx.x(xx.xx) 
 
   Median 
xx.x 
xx.x 
 
   Min, Max 
xx, xx 
xx, xx 
 
 
 
 
 
log(ER AQUA score at surgery)  
 
 
 
   n 
xxx 
xx 
 
   Mean (Standard Deviation) 
xx.x(xx.xx) 
xx.x(xx.xx) 
 
   Median 
xx.x 
xx.x 
 
   Min, Max 
xx, xx 
xx, xx 
 
 
 
 
 
log(ER AQUA score at surgery) - log(ER AQUA score at baseline) 
 
 
 
   n 
xxx 
xx 
 
   Mean (Standard Deviation) 
xx.x(xx.xx) 
xx.x(xx.xx) 
 
   Median 
xx.x 
xx.x 
 
   Min, Max 
xx, xx 
xx, xx 
 
   LSM (Standard Error)[1]  
xx.x(xx.xx) 
xx.x(xx.xx) 
xx.x(xx.xx) 
   80% Confidence Interval for LSM[1] 
xx.xx, xx.xx 
xx.xx, xx.xx 
 
   95% Confidence Interval for LSM[1] 
xx.xx, xx.xx 
xx.xx, xx.xx 
 
   80% Confidence Interval for LSM Difference[1] 
 
 
xx.xx, xx.xx 
   95% Confidence Interval for LSM Difference[1] 
 
 
xx.xx, xx.xx 
 
 
 
 
Ratio between ER AQUA score at Surgery and baseline 
 
 
 
   Geometric Means[2]  
xx.x 
xx.x 
xx.x 
   80% Confidence Interval for Geometric Means[2] 
xx.xx, xx.xx 
xx.xx, xx.xx 
 
   95% Confidence Interval for Geometric Means[2] 
xx.xx, xx.xx 
xx.xx, xx.xx  
 
   80% Confidence Interval for Geometric Means Difference[2] 
 
 
xx.xx, xx.xx 
   95% Confidence Interval for Geometric Means Difference[2] 
 
 
xx.xx, xx.xx 
 
 
 
 
Note: AQUA = absolute quantification score in arbitrary units. 
[1] Analysis based on an analysis of variance (ANOVA) model. 
[2] Back transformed values of [1]. 
Source: Listing 16.2.6.2. 
 
 
 


Arvinas Estrogen Receptor, Inc (Arvinas) 
 
 
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ARV-471-BC-201 
 
<Final 2.0> 
<date> / <time> / <program name> 
 
Page xxx of yyy 
 
81 
Table 14.2.5.1.1 
Summary of PR H-score Percentage Change at C1D15 from Baseline Value without Covariate   
Analysis Set: Full Analysis Set  
 
ARV-471 
200 mg N=XXX 
 Anastrozole  
1 mg N=XX 
Difference 
PR H-score at baseline 
 
 
 
   n 
xxx 
xx 
 
   Mean (Standard Deviation) 
xx.x(xx.xx) 
xx.x(xx.xx) 
 
   Median 
xx.x 
xx.x 
 
   Min, Max 
xx, xx 
xx, xx 
 
 
 
 
 
PR H-score at C1D15 
 
 
 
   n 
xxx 
xx 
 
   Mean (Standard Deviation) 
xx.x(xx.xx) 
xx.x(xx.xx) 
 
   Median 
xx.x 
xx.x 
 
   Min, Max 
xx, xx 
xx, xx 
 
 
 
 
 
PR H-score percentage change at C1D15 
 
 
 
   n 
xxx 
xx 
 
   Mean (Standard Deviation) 
xx.x(xx.xx) 
xx.x(xx.xx) 
 
   Median 
xx.x 
xx.x 
 
   Min, Max 
xx, xx 
xx, xx 
 
   LSM (Standard Error)[1] 
xx.x(xx.xx) 
xx.x(xx.xx) 
xx.x(xx.xx) 
   80% Confidence Interval for LSM[1] 
xx.xx, xx.xx 
xx.xx, xx.xx 
 
   95% Confidence Interval for LSM[1] 
xx.xx, xx.xx 
xx.xx, xx.xx 
 
   80% Confidence Interval for LSM Difference[1] 
 
 
xx.xx, xx.xx 
   95% Confidence Interval for LSM Difference[1] 
 
 
xx.xx, xx.xx 
 
 
 
 
 
 
 
 
Note: PR (progesterone receptor) H-score = (SCORE_1)*1 + (SCORE_2)*2 + (SCORE_3)*3 from PgR636 assessment. 
[1] Analysis based on an analysis of variance (ANOVA) model. 
Source: Listing 16.2.6.1. 
Programming Note:  
 
 
 


Arvinas Estrogen Receptor, Inc (Arvinas) 
 
 
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<Final 2.0> 
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82 
Table 14.2.5.1.2 
Summary of Log-Transformed PR H-score Change at C1D15 from Baseline Value without Covariate   
Analysis Set: Full Analysis Set  
 
ARV-471 
200 mg N=XXX 
 Anastrozole  
1 mg N=XX 
Difference 
log(PR H-score at baseline)  
 
 
 
   n 
xxx 
xx 
 
   Mean (Standard Deviation) 
xx.x(xx.xx) 
xx.x(xx.xx) 
 
   Median 
xx.x 
xx.x 
 
   Min, Max 
xx, xx 
xx, xx 
 
 
 
 
 
log(PR H-score at C1D15)  
 
 
 
   n 
xxx 
xx 
 
   Mean (Standard Deviation) 
xx.x(xx.xx) 
xx.x(xx.xx) 
 
   Median 
xx.x 
xx.x 
 
   Min, Max 
xx, xx 
xx, xx 
 
 
 
 
 
log(PR H-score at C1D15) - log(PR H-score at baseline) 
 
 
 
   n 
xxx 
xx 
 
   Mean (Standard Deviation) 
xx.x(xx.xx) 
xx.x(xx.xx) 
 
   Median 
xx.x 
xx.x 
 
   Min, Max 
xx, xx 
xx, xx 
 
   LSM (Standard Error)[1]  
xx.x(xx.xx) 
xx.x(xx.xx) 
xx.x(xx.xx) 
   80% Confidence Interval for LSM[1] 
xx.xx, xx.xx 
xx.xx, xx.xx 
 
   95% Confidence Interval for LSM[1] 
xx.xx, xx.xx 
xx.xx, xx.xx 
 
   80% Confidence Interval for LSM Difference[1] 
 
 
xx.xx, xx.xx 
   95% Confidence Interval for LSM Difference[1] 
 
 
xx.xx, xx.xx 
 
 
 
 
Ratio between PR H-score at C1D15 and baseline 
 
 
 
   Geometric Means[2]  
xx.x 
xx.x 
xx.x 
   80% Confidence Interval for Geometric Means[2] 
xx.xx, xx.xx 
xx.xx, xx.xx 
 
   95% Confidence Interval for Geometric Means[2] 
xx.xx, xx.xx 
xx.xx, xx.xx  
 
   80% Confidence Interval for Geometric Means Difference[2] 
 
 
xx.xx, xx.xx 
   95% Confidence Interval for Geometric Means Difference[2] 
 
 
xx.xx, xx.xx 
 
 
 
 
Note: PR (progesterone receptor) H-score = (SCORE_1)*1 + (SCORE_2)*2 + (SCORE_3)*3 from PgR636 assessment.  
[1] Analysis based on an analysis of variance (ANOVA) model. 
[2] Back transformed values of [1]. 
Source: Listing 16.2.6.1. 
 
 


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<Final 2.0> 
<date> / <time> / <program name> 
 
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83 
Table 14.2.5.2.1 
Summary of PR H-score Percentage Change at Surgery from Baseline Value without Covariate   
Analysis Set: Full Analysis Set  
 
ARV-471 
200 mg N=XXX 
 Anastrozole  
1 mg N=XX 
Difference 
PR H-score at baseline 
 
 
 
   n 
xxx 
xx 
 
   Mean (Standard Deviation) 
xx.x(xx.xx) 
xx.x(xx.xx) 
 
   Median 
xx.x 
xx.x 
 
   Min, Max 
xx, xx 
xx, xx 
 
 
 
 
 
PR H-score at surgery 
 
 
 
   n 
xxx 
xx 
 
   Mean (Standard Deviation) 
xx.x(xx.xx) 
xx.x(xx.xx) 
 
   Median 
xx.x 
xx.x 
 
   Min, Max 
xx, xx 
xx, xx 
 
 
 
 
 
PR H-score percentage change at surgery 
 
 
 
   n 
xxx 
xx 
 
   Mean (Standard Deviation) 
xx.x(xx.xx) 
xx.x(xx.xx) 
 
   Median 
xx.x 
xx.x 
 
   Min, Max 
xx, xx 
xx, xx 
 
   LSM (Standard Error)[1] 
xx.x(xx.xx) 
xx.x(xx.xx) 
xx.x(xx.xx) 
   80% Confidence Interval for LSM[1] 
xx.xx, xx.xx 
xx.xx, xx.xx 
 
   95% Confidence Interval for LSM[1] 
xx.xx, xx.xx 
xx.xx, xx.xx 
 
   80% Confidence Interval for LSM Difference[1] 
 
 
xx.xx, xx.xx 
   95% Confidence Interval for LSM Difference[1] 
 
 
xx.xx, xx.xx 
 
 
 
 
 
 
 
 
Note: PR (progesterone receptor) H-score = (SCORE_1)*1 + (SCORE_2)*2 + (SCORE_3)*3 from PgR636 assessment. 
[1] Analysis based on an analysis of variance (ANOVA) model. 
Source: Listing 16.2.6.1. 
Programming Note:  
 
 
 


Arvinas Estrogen Receptor, Inc (Arvinas) 
 
 
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<Final 2.0> 
<date> / <time> / <program name> 
 
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84 
Table 14.2.5.2.2 
Summary of Log-Transformed PR H-score Change at Surgery from Baseline Value without Covariate   
Analysis Set: Full Analysis Set  
 
ARV-471 
200 mg N=XXX 
 Anastrozole  
1 mg N=XX 
Difference 
log(PR H-score at baseline)  
 
 
 
   n 
xxx 
xx 
 
   Mean (Standard Deviation) 
xx.x(xx.xx) 
xx.x(xx.xx) 
 
   Median 
xx.x 
xx.x 
 
   Min, Max 
xx, xx 
xx, xx 
 
 
 
 
 
log(PR H-score at surgery)  
 
 
 
   n 
xxx 
xx 
 
   Mean (Standard Deviation) 
xx.x(xx.xx) 
xx.x(xx.xx) 
 
   Median 
xx.x 
xx.x 
 
   Min, Max 
xx, xx 
xx, xx 
 
 
 
 
 
log(PR H-score at surgery) - log(PR H-score at baseline) 
 
 
 
   n 
xxx 
xx 
 
   Mean (Standard Deviation) 
xx.x(xx.xx) 
xx.x(xx.xx) 
 
   Median 
xx.x 
xx.x 
 
   Min, Max 
xx, xx 
xx, xx 
 
   LSM (Standard Error)[1]  
xx.x(xx.xx) 
xx.x(xx.xx) 
xx.x(xx.xx) 
   80% Confidence Interval for LSM[1] 
xx.xx, xx.xx 
xx.xx, xx.xx 
 
   95% Confidence Interval for LSM[1] 
xx.xx, xx.xx 
xx.xx, xx.xx 
 
   80% Confidence Interval for LSM Difference[1] 
 
 
xx.xx, xx.xx 
   95% Confidence Interval for LSM Difference[1] 
 
 
xx.xx, xx.xx 
 
 
 
 
Ratio between PR H-score at surgery and baseline 
 
 
 
   Geometric Means[2]  
xx.x 
xx.x 
xx.x 
   80% Confidence Interval for Geometric Means[2] 
xx.xx, xx.xx 
xx.xx, xx.xx 
 
   95% Confidence Interval for Geometric Means[2] 
xx.xx, xx.xx 
xx.xx, xx.xx  
 
   80% Confidence Interval for Geometric Means Difference[2] 
 
 
xx.xx, xx.xx 
   95% Confidence Interval for Geometric Means Difference[2] 
 
 
xx.xx, xx.xx 
 
 
 
 
Note: PR (progesterone receptor) H-score = (SCORE_1)*1 + (SCORE_2)*2 + (SCORE_3)*3 from PgR636 assessment. 
[1] Analysis based on an analysis of variance (ANOVA) model. 
[2] Back transformed values of [1]. 
Source: Listing 16.2.6.1. 
 




Arvinas Estrogen Receptor, Inc (Arvinas) 
 
 
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86 
Table 14.3.2.1 
Summary of Treatment Emergent Adverse Events by System Organ Class and Preferred Term     
Analysis Set: Safety Analysis Set                
System organ class 
   Preferred Term 
   ARV-471     
200 mg N=XXX 
 Anastrozole  
1 mg N=XX 
Total 
N=XXX 
 
 
 
 
Subjects with any TEAE, n(%) 
XX(XX.X) 
XX(XX.X) 
XX(XX.X) 
 
 
 
 
System organ class 1  
XX(XX.X) 
XX(XX.X) 
XX(XX.X) 
  Preferred Term 1   
XX(XX.X) 
XX(XX.X) 
XX(XX.X) 
  Preferred Term 2 
XX(XX.X) 
XX(XX.X) 
XX(XX.X) 
 
 
 
 
System organ class 2 
XX(XX.X) 
XX(XX.X) 
XX(XX.X) 
  Preferred Term 1  
XX(XX.X) 
XX(XX.X) 
XX(XX.X) 
  Preferred Term 2 
XX(XX.X) 
XX(XX.X) 
XX(XX.X) 
 
 
 
 
Note: Adverse events are coded using Medical Dictionary for Regulatory Activities (MedDRA) version 27.0. 
Note: A TEAE is an AE that emerges or worsens (ie increase in CTCAE grade) on/after the first dose of ARV-
471/Anastrozole to 30 days from the last administration of the study intervention (ie, study drug treatment or surgical resection, 
whichever occurs last). 
Source: Listings 16.2.7.1. 
 
Programming Note:  
 
 
 
 


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87 
Repeat the following tables with Table 14.3.2.1 shell 
 
Table 14.3.2.2 
Summary of Treatment Emergent Adverse Events Related to Study Drug by System Organ Class  
and Preferred Term  
Analysis Set: Safety Analysis Set   
Programming Note: update “Subjects with any TEAE” to “Subjects with any TEAE Related to Study Drug” 
 
 
Table 14.3.2.3 
Summary of Treatment Emergent Adverse Events with Grade 3 or Higher by System Organ Class  
and Preferred Term  
Analysis Set: Safety Analysis Set  
Programming Note: update “Subjects with any TEAE” to “Subjects with any Grade 3 or higher TEAE” 
 
 
Table 14.3.2.4 
Summary of Treatment Emergent Adverse Events with Grade 3 or Higher Related to Study Drug by System Organ Class  
and Preferred Term  
Analysis Set: Safety Analysis Set  
Programming Note: update “Subjects with any TEAE” to “Subjects with any Grade 3 or higher TEAE Related to Study Drug” 
 
 
Table 14.3.2.5.1 
Summary of Treatment Emergent Adverse Events Leading to Drug Withdrawn by System Organ Class  
and Preferred Term  
Analysis Set: Safety Analysis Set  
Programming Note: 
update “Subjects with any TEAE” to “Subjects with any TEAE Leading to Drug Withdrawn” 
 
 


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88 
Table 14.3.2.5.2 
Summary of Treatment Emergent Adverse Events Related to Study Drug Leading to Drug Withdrawn  
by System Organ Class and Preferred Term  
Analysis Set: Safety Analysis Set  
Programming Note: 
update “Subjects with any TEAE” to “Subjects with any TEAE Related to Study Drug Leading to Drug Withdrawn” 
 
Table 14.3.2.6.1 
Summary of Treatment Emergent Adverse Events Leading to Drug Interrupted by System Organ Class  
and Preferred Term  
Analysis Set: Safety Analysis Set  
Programming Note:  
update “Subjects with any TEAE” to “Subjects with any TEAE Leading to Drug Interrupted” 
 
Table 14.3.2.6.2 
Summary of Treatment Emergent Adverse Events Related to Study Drug Leading to Drug Interrupted  
by System Organ Class and Preferred Term  
Analysis Set: Safety Analysis Set  
Programming Note:  
update “Subjects with any TEAE” to “Subjects with any TEAE Related to Study Drug Leading to Drug Interrupted” 
 
 
Table 14.3.2.7.1 
Summary of Treatment Emergent Adverse Events Leading to Dose Reduced by System Organ Class  
and Preferred Term  
Analysis Set: Safety Analysis Set  
Programming Note:  
update “Subjects with any TEAE” to “Subjects with any TEAE Leading to Dose Reduced” 
 
Table 14.3.2.7.2 
Summary of Treatment Emergent Adverse Events Related to Study Drug Leading to Dose Reduced  
by System Organ Class and Preferred Term  
Analysis Set: Safety Analysis Set  
Programming Note:  
update “Subjects with any TEAE” to “Subjects with any TEAE Related to Study Drug Leading to Dose Reduced” 


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89 
Table 14.3.2.8 
Summary of Treatment Emergent Adverse Events by Preferred Term  
Analysis Set: Safety Analysis Set                                                           
Preferred Term 
ARV-471 
200 mg N=XX 
 Anastrozole  
1 mg N=XX 
Total 
N=XXX 
 
 
 
 
Subjects with any TEAE, n(%)   
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
 
 
 
 
Preferred Term 1     
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
Preferred Term 2 
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
Preferred Term 3  
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
Preferred Term 4 
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
 
 
 
 
Note: Adverse events are coded using Medical Dictionary for Regulatory Activities (MedDRA) version 27.0. 
Note: A TEAE is an AE that emerges or worsens (ie increase in CTCAE grade) on/after the first dose of ARV-
471/Anastrozole to 30 days from the last administration of the study intervention (ie, study drug treatment or surgical resection, 
whichever occurs last). 
Source: Listings 16.2.7.1. 
 
Programming Note:  
 
 
Repeat the following tables with Table 14.3.2.8 shell 
 
Table 14.3.2.9 
Summary of Treatment Emergent Adverse Events Related to Study Drug by Preferred Term  
Analysis Set: Safety Analysis Set  
Programming Note: update “Subjects with any TEAE” to “Subjects with any TEAE Related to Study Drug” 
 
 


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90 
Table 14.3.2.10 
 Summary of Treatment Emergent Adverse Events by System Organ Class,  
Preferred Term and Maximum CTCAE Grade  
Analysis Set: Safety Analysis Set  
System organ class 
   Preferred Term 
      CTCAE Grade 
ARV-471 
200 mg N=XXX 
 Anastrozole 
1 mg N=XX 
Total 
N=XXX 
 
 
 
 
Subjects with any TEAE, n(%) 
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
  Grade 1 
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
  Grade 2 
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
  Grade 3 
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
  Grade 4 
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
  Grade 5 
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
 
 
 
 
System organ class 1 
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
  Grade 1 
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
  Grade 2 
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
  Grade 3 
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
  Grade 4 
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
  Grade 5 
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
 
 
 
 
  Preferred Term 1  
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
     Grade 1 
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
     Grade 2 
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
     Grade 3 
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
     Grade 4 
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
     Grade 5 
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
 
 
 
 
 
Note: Adverse events are coded using Medical Dictionary for Regulatory Activities (MedDRA) version 27.0, and graded according to the 
NCI-CTCAE version 5.0. 
Note: A TEAE is an AE that emerges or worsens (ie increase in CTCAE grade) on/after the first dose of ARV-
471/Anastrozole to 30 days from the last administration of the study intervention (ie, study drug treatment or surgical resection, 
whichever occurs last). 
Source: Listings 16.2.7.1. 
Repeat the following tables with Table 14.3.2.10 shell 
Table 14.3.2.11 
Summary of Treatment Emergent Adverse Events Related to Study Drug by System Organ Class,  
Preferred Term and Maximum CTCAE Grade  
Analysis Set: Safety Analysis Set 
Programming Note: update “Subjects with any TEAE” to “Subjects with any TEAE Related to Study Drug” 
 
 


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Table 14.3.2.12 
Summary of MedDRA SMQ for Torsade de Pointes by Preferred Term and Maximum CTCAE Grade  
Analysis Set: Safety Analysis Set                                                           
Preferred Term 
  CTCAE Grade 
ARV-471 
200 mg N=XX 
 Anastrozole  
1 mg N=XX 
Total 
N=XXX 
 
 
 
 
Subjects with any SMQ for Torsade de Pointes, n(%)   
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
  Grade 1 
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
  Grade 2 
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
  Grade 3 
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
  Grade 4 
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
  Grade 5 
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
 
 
 
 
Preferred Term 1  
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
  Grade 1 
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
  Grade 2 
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
  Grade 3 
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
  Grade 4 
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
  Grade 5 
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
 
 
 
 
Preferred Term 2 
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
  Grade 1 
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
  Grade 2 
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
  Grade 3 
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
  Grade 4 
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
  Grade 5 
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
 
 
 
 
 
Note: Adverse events are coded using Medical Dictionary for Regulatory Activities (MedDRA) version 27.0, and graded according to the 
NCI-CTCAE version 5.0. 
Source: Listings 16.2.7.1. 
 
Programming Note:  
PTs include Electrocardiogram QT interval abnormal, Electrocardiogram QT prolonged, Long QT syndrome, Long QT syndrome 
congenital, Torsade de pointes, Ventricular tachycardia, Arrhythmic storm, Cardiac arrest, Cardiac death, Cardiac fibrillation, Cardio-
respiratory arrest, Electrocardiogram repolarisation abnormality, Electrocardiogram U wave inversion, Electrocardiogram U wave 
present, Electrocardiogram U-wave abnormality, Loss of consciousness, Seizure, Sudden cardiac death, Sudden death, Syncope, 
Ventricular arrhythmia, Ventricular fibrillation, Ventricular flutter, Ventricular tachyarrhythmia. 
 
 


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92 
Repeat the following tables with Table 14.3.2.1 shell 
 
Table 14.3.3.1 
Summary of Serious Treatment Emergent Adverse Events by System Organ Class   
and Preferred Term  
Analysis Set: Safety Analysis Set  
Programming Note:  
update “Subjects with any TEAE” to “Subjects with any Serious TEAE” 
update “Source: Listings 16.2.7.1. ” to “Source: Listings 16.2.7.2.” 
 
 
 
 
Table 14.3.3.2 
Summary of Serious Treatment Emergent Adverse Events Related to Study Drug by System Organ Class  
and Preferred Term  
Analysis Set: Safety Analysis Set  
Programming Note: 
update “Subjects with any TEAE” to “Subjects with any Serious TEAE Related to Study Drug” 
update “Source: Listings 16.2.7.1. ” to “Source: Listings 16.2.7.2.” 
 
 
 
Repeat the following tables with Table 14.3.2.8 shell 
Table 14.3.3.3 
Summary of Serious Treatment Emergent Adverse Events by Preferred Term  
Analysis Set: Safety Analysis Set  
Programming Note:  
update “Subjects with any TEAE” to “Subjects with any Serious TEAE” 
update “Source: Listings 16.2.7.1. ” to “Source: Listings 16.2.7.2.” 
 
 


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Table 14.3.3.4 
Summary of Serious Treatment Emergent Adverse Events Related to Study Drug by Preferred Term  
Analysis Set: Safety Analysis Set  
Programming Note: 
update “Subjects with any TEAE” to “Subjects with any Serious TEAE Related to Study Drug” 
update “Source: Listings 16.2.7.1. ” to “Source: Listings 16.2.7.2.” 
 
 
Repeat the following tables with Table 14.3.2.10 shell 
 
Table 14.3.3.5 
Summary of Serious Treatment Emergent Adverse Events by System Organ Class,  
Preferred Term and Maximum CTCAE Grade 
Analysis Set: Safety Analysis Set  
Programming Note:  
update “Subjects with any TEAE” to “Subjects with any Serious TEAE” 
update “Source: Listings 16.2.7.1. ” to “Source: Listings 16.2.7.2.” 
 
 
Table 14.3.3.6 
Summary of Serious Treatment Emergent Adverse Events Related to Study Drug by System Organ Class,  
Preferred Term and Maximum CTCAE Grade  
Analysis Set: Safety Analysis Set   
Programming Note: 
update “Subjects with any TEAE” to “Subjects with any Serious TEAE Related to Study Drug” 
update “Source: Listings 16.2.7.1. ” to “Source: Listings 16.2.7.2.” 
 
 
 
Repeat the following tables with Table 14.3.2.1 shell 
 
 
Table 14.3.3.7 
Summary of Treatment Emergent Adverse Events Leading to Death by System Organ Class  


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and Preferred Term  
Analysis Set: Safety Analysis Set  
Programming Note:  
update “Subjects with any TEAE” to “Subjects with any TEAE Leading to Death” 
 


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Table 14.3.3.8 
 Summary of Subject Death  
Analysis Set: Safety Analysis Set                           
 
ARV-471 
200 mg N=XXX 
 Anastrozole 
1 mg N=XX 
Total 
N=XXX 
 
 
 
 
Number of Subject Death, n(%)  
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
 
 
 
 
Reason of Subject Death, n(%) 
 
 
 
   Disease progression  
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
   Adverse Event 
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
   Unknown 
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
   Other 
XXX(XX.X) 
XX(XX.X) 
XXX(XX.X) 
 
 
 
 
Source: Listing 16.2.1.1. 
 
Programming Note:  
 
 




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97 
Repeat the following tables with Table 14.3.7.1 shell 
 
Table 14.3.7.3 
Summary of Coagulation Laboratory by Visit  
Analysis Set: Safety Analysis Set    
 
Replace ‘Source: Listing 16.2.8.3’ with ‘Source: Listing 16.2.8.5’ 
 
 
 
Table 14.3.7.5 
Summary of Serum Chemistry Laboratory by Visit  
Analysis Set: Safety Analysis Set  
 
Replace ‘Source: Listing 16.2.8.3’ with ‘Source: Listing 16.2.8.4’ 
 
 
 
 
 
 


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Table 14.3.7.2.1 
Shift of Hematology CTCAE Grade from Baseline to Worst Post-baseline  
Analysis Set: Safety Analysis Set 
                  
Test: Anemia  
 
 
Worst Post-baseline CTCAE Grade, n(%)    
Baseline  
CTCAE Grade 
Missing 
0 
1 
2 
3 
4 
Total 
ARV-471200 mg (N=XXX)  
Missing 
XX(XX.X) 
XX(XX.X) 
XX(XX.X) 
XX(XX.X) 
XX(XX.X) 
XX(XX.X) 
XX(XX.X) 
0  
XX(XX.X) 
XX(XX.X) 
XX(XX.X) 
XX(XX.X) 
XX(XX.X) 
XX(XX.X) 
XX(XX.X) 
1 
XX(XX.X) 
XX(XX.X) 
XX(XX.X) 
XX(XX.X) 
XX(XX.X) 
XX(XX.X) 
XX(XX.X) 
2 
XX(XX.X) 
XX(XX.X) 
XX(XX.X) 
XX(XX.X) 
XX(XX.X) 
XX(XX.X) 
XX(XX.X) 
3 
XX(XX.X) 
XX(XX.X) 
XX(XX.X) 
XX(XX.X) 
XX(XX.X) 
XX(XX.X) 
XX(XX.X) 
4 
XX(XX.X) 
XX(XX.X) 
XX(XX.X) 
XX(XX.X) 
XX(XX.X) 
XX(XX.X) 
XX(XX.X) 
Total 
XX(XX.X) 
XX(XX.X) 
XX(XX.X) 
XX(XX.X) 
XX(XX.X) 
XX(XX.X) 
XX(100) 
 
 
 
 
 
 
 
 
Anastrozole 1 mg (N=XX) 
Missing 
XX(XX.X) 
XX(XX.X) 
XX(XX.X) 
XX(XX.X) 
XX(XX.X) 
XX(XX.X) 
XX(XX.X) 
0  
XX(XX.X) 
XX(XX.X) 
XX(XX.X) 
XX(XX.X) 
XX(XX.X) 
XX(XX.X) 
XX(XX.X) 
1 
XX(XX.X) 
XX(XX.X) 
XX(XX.X) 
XX(XX.X) 
XX(XX.X) 
XX(XX.X) 
XX(XX.X) 
2 
XX(XX.X) 
XX(XX.X) 
XX(XX.X) 
XX(XX.X) 
XX(XX.X) 
XX(XX.X) 
XX(XX.X) 
3 
XX(XX.X) 
XX(XX.X) 
XX(XX.X) 
XX(XX.X) 
XX(XX.X) 
XX(XX.X) 
XX(XX.X) 
4 
XX(XX.X) 
XX(XX.X) 
XX(XX.X) 
XX(XX.X) 
XX(XX.X) 
XX(XX.X) 
XX(XX.X) 
Total 
XX(XX.X) 
XX(XX.X) 
XX(XX.X) 
XX(XX.X) 
XX(XX.X) 
XX(XX.X) 
XX(100) 
 
 
 
 
 
 
 
 
Total (N=XXX) 
Missing 
XX(XX.X) 
XX(XX.X) 
XX(XX.X) 
XX(XX.X) 
XX(XX.X) 
XX(XX.X) 
XX(XX.X) 
0  
XX(XX.X) 
XX(XX.X) 
XX(XX.X) 
XX(XX.X) 
XX(XX.X) 
XX(XX.X) 
XX(XX.X) 
1 
XX(XX.X) 
XX(XX.X) 
XX(XX.X) 
XX(XX.X) 
XX(XX.X) 
XX(XX.X) 
XX(XX.X) 
2 
XX(XX.X) 
XX(XX.X) 
XX(XX.X) 
XX(XX.X) 
XX(XX.X) 
XX(XX.X) 
XX(XX.X) 
3 
XX(XX.X) 
XX(XX.X) 
XX(XX.X) 
XX(XX.X) 
XX(XX.X) 
XX(XX.X) 
XX(XX.X) 
4 
XX(XX.X) 
XX(XX.X) 
XX(XX.X) 
XX(XX.X) 
XX(XX.X) 
XX(XX.X) 
XX(XX.X) 
Total 
XX(XX.X) 
XX(XX.X) 
XX(XX.X) 
XX(XX.X) 
XX(XX.X) 
XX(XX.X) 
XXX(100) 
 
 
 
 
 
 
 
 
Note: The baseline value is defined to be the last non-missing assessment on/before the date of the first ARV-
471/anastrozole dose. 
Note: Grade is derived using CTCAE 5.0. 
Source: Listing 16.2.8.3. 
 
Programming Note:  
Each Test starts from a new page  
 
 
 


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Table 14.3.7.2.2 
Summary of Hematology CTCAE On-Treatment Worsening 
Analysis Set: Safety Analysis Set 
                 
ARV-471 200 mg N=XXX 
 
Anastrozole 1 mg N=XX 
N’ 
Worsened from Baseline, n(%) 
 
N’ 
Worsten from Baseline, n(%) 
Neutrophil count decreased 
XXX 
XX(XX.X) 
 
XXX 
XX(XX.X) 
White blood cell count decrease 
XXX 
XX(XX.X) 
 
XXX 
XX(XX.X) 
Anemia 
XXX 
XX(XX.X) 
 
XXX 
XX(XX.X) 
Platelat count decreased 
XXX 
XX(XX.X) 
 
XXX 
XX(XX.X) 
 
 
 
 
 
Note: The baseline value is defined to be the last non-missing assessment on/before the date of the first ARV-
471/anastrozole dose. 
Note: Include lab data up to 28 days after the last dose of study intervention, which is grade using CTCAE 5.0. 
Note: N’ is the number of participants with baseline and at least on on-treatment assessment for the parameter of 
interest. It is the denominator of the percentage. n is the number of participants with CTCAE grade of on-treatment lab 
results worsten than baseline CTCAE grade.  
Note: Treatment-worsening shift includes grade 0 baseline to grade 1/2/3/4 postbaseline, grade 1 at baseline to grade 
2/3/4 postbaseline, grade 2 at baseline to grade 3/4 postbaseline, or grade 3 at baseline to grade 4 postbaseline. 
Source: Listing 16.2.8.3 
 
Programming Note:  
 
 
 
  
 
 


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Repeat the following tables with Table 14.3.7.2.1 shell 
 
Table 14.3.7.4 
Shift of Coagulation CTCAE Grade from Baseline to Worst Post-baseline  
Analysis Set: Safety Analysis Set  
 
Replace ‘Source: Listing 16.2.8.3’ with ‘Source: Listing 16.2.8.5’ 
 
 
Table 14.3.7.6 
Shift of Serum Chemistry CTCAE Grade from Baseline to Worst Post-baseline  
Analysis Set: Safety Analysis Set  
 
 
Replace ‘Source: Listing 16.2.8.3’ with ‘Source: Listing 16.2.8.4’ 
 
 
































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Figure 14.3.2.8  
Tornado Plot for Treatment Emergent Adverse Events by Preferred Term  
Analysis Set: Safety Analysis Set  
Note: Adverse events are coded using Medical Dictionary for Regulatory Activities (MedDRA) version 27.0. 
Note: A TEAE is an AE that emerges or worsens (ie increase in CTCAE grade) on/after the first dose of ARV-
471/Anastrozole to 30 days from the last administration of the study intervention (ie, study drug treatment or surgical resection, 
whichever occurs last). 
Source: Table 14.3.2.8, Table 14.3.2.3 and Listings 16.2.7.1. 
Programming Note:  
x Add figure legend to indicate Arm A and Arm B  color.  
 
 
 
 
 
 
 
in >= 5% Subjects 
Grade 3 or higher 






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Listing 16.2.2 
Deviations from the Clinical Protocol 
Analysis Set: Full Analysis Set  
Randomized Treatment: ARV-471 200 mg 
Subject 
ID  
Date of Protocol  
Deviation (Study 
Day)  
        
Protocol Deviation Description 
Protocol Deviation Category  
Protocol 
Deviation 
Severity  
XXXX-XXX 
DDMMMYYYY (xx) 
XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX 
XXXXXXXXXXXX 
Minor 
DDMMMYYYY (xx) 
XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX 
XXXXXXXXXXXXXXXXXXXXXXXXXX 
Minor 
DDMMMYYYY (xx) 
XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX 
XXXXXXXXXXXXXXXXXXXXXX 
Minor 
XXXX-XXX 
DDMMMYYYY (xx) 
XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX 
XXXXXXXXXXXXXXXXXXXXXXXXXX 
Minor 
XXXX-XXX 
DDMMMYYYY (xx) 
XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX 
XXXXXXXXXXXXXXXXXXXXXX 
Minor 
 
 
 
 
Note: Day 1 is the date of first ARV-471/anastrozole dose. Study Day = Assessment Date – Date of Day 1 + 1 for 
assessment dates on or after date of Day 1. Study Day = Assessment Date – Date of Day 1 for assessment prior to Day 1. 
 
 
Programming Note:  
x Sorting order is by Subject ID, Date of Protocol Deviation.  
 
  
 


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Listing 16.2.4.1 
Demographic Characteristics  
Analysis Set: Full Analysis Set 
Randomized Treatment: ARV-471 200 mg  
 Subject 
ID 
Year of 
Birth/Age 
(years) 
Sex/  
Ethnicity  
Race  
Weight (kg) 
at Baseline 
Height (cm) 
at Baseline 
ECOG 
Performance 
Status at 
Baseline  
XXXX-XXX 
YYYY/XX 
Female 
Hispanic or Latino 
American Indian or Alaskan Native 
xxx.x 
xxx.x 
0 
XXXX-XXX 
YYYY/XX 
Female 
Not Hispanic or Latino 
Asian 
xxx.x 
xxx.x 
0 
XXXX-XXX 
YYYY/XX 
Female 
Not Reported 
Black or African American  
xxx.x 
xxx.x 
1 
XXXX-XXX 
YYYY/XX 
Female 
Not Reported 
Native Hawaiian or Other Pacific Islander 
xxx.x 
xxx.x 
1 
XXXX-XXX 
YYYY/XX 
Female 
Not Hispanic or Latino 
White 
xxx.x 
xxx.x 
1 
XXXX-XXX 
YYYY/XX 
Female 
Not Hispanic or Latino 
Not Reported 
xxx.x 
xxx.x 
1 
XXXX-XXX 
YYYY/XX 
Female 
Not Hispanic or Latino 
White 
xxx.x 
xxx.x 
0 
XXXX-XXX 
YYYY/XX 
Female 
Not Reported 
Other: XXXXXX 
xxx.x 
xxx.x 
1 
 
 
 
 
 
 
 
 
 
 
 
Programming Note:  
x  Sorting order is by Subject ID.  
 
 
 
 
 


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Listing 16.2.4.2 
Medical History 
Analysis Set: Full Analysis Set  
Randomized Treatment: ARV-471 200 mg  
Subject  
ID 
Category  
System Organ Class/ 
Preferred Term/  
Medical Condition or Past Surgery Term  
Start Date  
(Study Day)/ 
Stop Date   
(Study Day) 
CTCAE Grade 
Taking 
Medication for 
Condition? 
XXXX-XXX 
Medical Condition 
XXXXXXXXXXXXXXXXXXXXX/ 
XXXXXXXXXXXXXXXXXXX/ 
XXXXXXXXXXXXXXXXXXXXXX 
DDMMMYYY (xx)/ 
Ongoing 
Grade 1  
No 
 
Medical Condition 
XXXXXXXXXXXXXXXXXXXXX/ 
XXXXXXXXXXXXXXXXXXX/ 
XXXXXXXXXXXXXXXXXXXXXX 
DDMMMYYY (xx)/ 
DDMMMYYY (xx) 
Grade 2 
Yes 
 
Surgery 
XXXXXXXXXXXXXXXXXXXXX/ 
XXXXXXXXXXXXXXXXXXX/ 
XXXXXXXXXXXXXXXXXXXXXX 
DDMMMYYY (xx)/ 
DDMMMYYY (xx) 
Grade 3 
Yes 
XXXX-XXX 
Medical Condition 
XXXXXXXXXXXXXXXXXXXXX/ 
XXXXXXXXXXXXXXXXXXX/ 
XXXXXXXXXXXXXXXXXXXXXX 
DDMMMYYY (xx)/ 
DDMMMYYY (xx) 
Grade 4 
Yes 
 
Medical Condition 
XXXXXXXXXXXXXXXXXXXXX/ 
XXXXXXXXXXXXXXXXXXX/ 
XXXXXXXXXXXXXXXXXXXXXX 
DDMMMYYY (xx)/ 
DDMMMYYY (xx) 
Grade 1  
No 
 
Medical Condition 
XXXXXXXXXXXXXXXXXXXXX/ 
XXXXXXXXXXXXXXXXXXX/ 
XXXXXXXXXXXXXXXXXXXXXX 
DDMMMYYY (xx)/ 
Ongoing 
Grade 2 
Yes 
 
Medical Condition 
XXXXXXXXXXXXXXXXXXXXX/ 
XXXXXXXXXXXXXXXXXXX/ 
XXXXXXXXXXXXXXXXXXXXXX 
DDMMMYYY (xx)/ 
Ongoing 
Grade 1  
Yes 
 
 
 
 
 
 
Note: Day 1 is the date of first ARV-471/anastrozole dose. Study Day = Assessment Date – Date of Day 1 + 1 for 
assessment dates on or after date of Day 1. Study Day = Assessment Date – Date of Day 1 for assessment prior to Day 1. 
Note: Medical Condition/Past Surgery was coded with MedDRA version 24.1. 
 
 
Programming Note:  
Sorting order is by Subject ID, System Organ Class, Preferred Term. 
 
 
 


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122 
Listing 16.2.4.3 
Disease Staging - Initial Diagnosis  
Analysis Set: Full Analysis Set 
Randomized Treatment: ARV-471 200 mg  
Subject  
ID  
 
Date of Initial 
Diagnosis  
(Study Day) 
 
Primary 
Diagnosis 
 
Disease Stage 
at Initial 
Diagnosis 
 
Primary Tumor/ 
Regional Lymph Node/ 
Distant Metastasis 
 
Histopathological 
Classification 
 
Histopathological 
Grade 
 
XXXX-XXX 
DDMMMYYY(xx) 
ER+ HER2- BC 
Stage 0  
TX/cNX/Unknown  
In-Situ Carcinoma  
Grade 1 
XXXX-XXX 
DDMMMYYY(xx) 
ER+ HER2- BC 
Stage IA 
T0/cN0/M0 
Invasive Ductal Carcinoma 
Grade 3 
XXXX-XXX 
DDMMMYYY(xx) 
ER+ HER2- BC 
Stage IB 
Tis/cN1/M1 
Invasive Lobular Carcinoma 
Grade 1 
XXXX-XXX 
DDMMMYYY(xx) 
ER+ HER2- BC 
Stage IIA 
T1mi/cN2a/M0 
Invasive Carcinoma NOS 
Grade x 
XXXX-XXX 
DDMMMYYY(xx) 
ER+ HER2- BC 
Stage IIB 
T1a/cN2b/M0 
Invasive Mucinous 
Grade 1 
XXXX-XXX 
DDMMMYYY(xx) 
ER+ HER2- BC 
Stage IIIA  
T1b/cN2c/M0 
Adenocarcinoma 
Grade 2 
XXXX-XXX 
DDMMMYYY(xx) 
ER+ HER2- BC 
Unknown 
T1c/cN3c/M1  
Other: XXXXXXX 
Grade 1 
 
 
 
 
 
 
 
Note: Day 1 is the date of first ARV-471/anastrozole dose. Study Day = Assessment Date – Date of Day 1 + 1 for 
assessment dates on or after date of Day 1. Study Day = Assessment Date – Date of Day 1 for assessment prior to Day 1. 
Note: BC = Breast Cancer. 
 
 
Programming Note:  
x Sorting order is by Subject ID 
 


Arvinas Estrogen Receptor, Inc (Arvinas) 
 
 
CONFIDENTIAL 
ARV-471-BC-201 
 
<Final 2.0> 
<date> / <time> / <program name> 
 
Page xxx of yyy 
 
123 
Listing 16.2.4.4 
Disease Staging - Current Diagnosis  
Analysis Set: Full Analysis Set 
Randomized Treatment: ARV-471 200 mg  
Subject  
ID  
Date of Current 
Staging  
(Study Day) 
 
Primary 
Diagnosis 
 
Disease Stage 
at Initial 
Diagnosis 
 
Primary Tumor/ 
Regional Lymph Node/ 
Distant Metastasis 
 
Histopathological  
Classification/ 
Histopathological Grade 
 
Imaging 
Modality/  
Planned Type 
of Surgery 
 
XXXX-XXX 
DDMMMYYY(xx) 
ER+ HER2- BC 
Stage 0  
TX/cNX/Unknown  
In-Situ Carcinoma/1  
CT/Mastectomy 
XXXX-XXX 
DDMMMYYY(xx) 
ER+ HER2- BC 
Stage IA 
T0/cN0/M0 
Invasive Ductal Carcinoma/3 
MRI/Mastectomy 
XXXX-XXX 
DDMMMYYY(xx) 
ER+ HER2- BC 
Stage IB 
Tis/cN1/M1 
Invasive Lobular Carcinoma/2 
Ultrasound/BCS 
XXXX-XXX 
DDMMMYYY(xx) 
ER+ HER2- BC 
Stage IIA 
T1mi/cN2a/M0 
Invasive Carcinoma NOS/2 
Mammogram/BCS 
XXXX-XXX 
DDMMMYYY(xx) 
ER+ HER2- BC 
Stage IIB 
T1a/cN2b/M0 
Invasive Mucinous/1 
PET-CT/BCS 
XXXX-XXX 
DDMMMYYY(xx) 
ER+ HER2- BC 
Stage IIIA  
T1b/cN2c/M0 
Adenocarcinoma/1 
PET-MRI/BCS 
XXXX-XXX 
DDMMMYYY(xx) 
ER+ HER2- BC 
Unknown 
T1c/cN3c/M1  
Other: XXXXXXX/X 
CT/BCS 
 
 
 
 
 
 
 
Note: Day 1 is the date of first ARV-471/anastrozole dose. Study Day = Assessment Date – Date of Day 1 + 1 for 
assessment dates on or after date of Day 1. Study Day = Assessment Date – Date of Day 1 for assessment prior to Day 1. 
Note: BC = Breast Cancer; BCS = Breast conserving surgery.  
 
 
 
Programming Note:  
x Sorting order is by Subject ID 
  
 


Arvinas Estrogen Receptor, Inc (Arvinas) 
 
 
CONFIDENTIAL 
ARV-471-BC-201 
 
<Final 2.0> 
<date> / <time> / <program name> 
 
Page xxx of yyy 
 
124 
Listing 16.2.4.5 
Molecular Biology of Disease   
Analysis Set: Full Analysis Set 
Randomized Treatment: ARV-471 200 mg  
Subject  
ID  
Analyte/ 
Biomarker 
 
Date of 
Collection 
(Study Day) 
 
Specimen  
Type 
 
Sample Site 
 
Analytical 
Method/Result 
 
Quantitative 
Parameter 
 
Quantitative 
Result (%) 
 
XXXX-XXX 
HER2 
DDMMMYYY(xx) Tumor tissue  
Breast  
IHC/1+ 
 
 
 
KI67  
DDMMMYYY(xx) Tumor tissue  Lymph Node 
 
Tumor cells 
xx.x 
 
Estrogen receptor 
DDMMMYYY(xx) Tumor tissue  Other: XXXXX  
 
Tumor cells 
xx.x 
 
Progesterone receptor DDMMMYYY(xx) Tumor tissue  
Breast  
 
Tumor cells 
xx.x 
XXXX-XXX 
HER2 
DDMMMYYY(xx) Tumor tissue  
Breast  
ISH/Negative 
 
 
 
KI67  
DDMMMYYY(xx) Tumor tissue  
Breast  
 
Tumor cells 
xx.x 
 
Estrogen receptor 
DDMMMYYY(xx) Tumor tissue  Other: XXXXX 
 
Tumor cells 
xx.x 
 
Progesterone receptor DDMMMYYY(xx) Tumor tissue  Other: XXXXX 
 
Tumor cells 
xx.x 
Note: Day 1 is the date of first ARV-471/anastrozole dose. Study Day = Assessment Date – Date of Day 1 + 1 for 
assessment dates on or after date of Day 1. Study Day = Assessment Date – Date of Day 1 for assessment prior to Day 1. 
* indicates the baseline value. 
 
 
Programming Note:  
Sorting order is by Subject ID, Analyte/Biomarker, Date of Collection. 
Include data in ‘Molecular Biology of Disease - HER2 Status’ and ‘Molecular Biology of Disease - Hormone Receptor/KI67 Status’ 
 
 


Arvinas Estrogen Receptor, Inc (Arvinas) 
 
 
CONFIDENTIAL 
ARV-471-BC-201 
 
<Final 2.0> 
<date> / <time> / <program name> 
 
Page xxx of yyy 
 
125 
Listing 16.2.4.6 
Prior and Concomitant Medications  
Analysis Set: Full Analysis Set 
Randomized Treatment: ARV-471 200 mg  
Subject  
ID  
Prior or 
Concomitant 
 
ATC Category II/ 
Preferred Name/  
 Medication Name 
 
Start Date (Study Day)/ 
 
Stop Date (Study Day) 
 
Dose/ 
  
Unit   
Frequency/ 
 Route 
  
Use  
XXXX-XXX 
Prior 
XXXXXXXXXXXXXX/ 
XXXXXXXXXXXXX/ 
XXXXXXXXXXXXXXX 
DDMMMYYY (XX)/ 
Ongoing 
XX/ 
Capsule 
TID/ 
Oral  
AE:#1, #5 
 
Concomitant 
XXXXXXXXXXXXXX/ 
XXXXXXXXXXXXX/ 
XXXXXXXXXXXXXXX 
DDMMMYYY (XX)/ 
DDMMMYYY (XX) 
XX/  
Gram 
QIS/ 
Intramuscular 
MH  
 
Concomitant 
XXXXXXXXXXXXXX/ 
XXXXXXXXXXXXX/ 
XXXXXXXXXXXXXXX 
DDMMMYYY (XX)/ 
DDMMMYYY (XX) 
XX/  
Microgram 
BID/ 
Subcutaneous 
MH 
 
XXXX-XXX 
Concomitant 
XXXXXXXXXXXXXX/ 
XXXXXXXXXXXXX/ 
XXXXXXXXXXXXXXX 
DDMMMYYY (XX)/ 
DDMMMYYY (XX) 
XX/  
Spray 
UNKNOWN / 
Topical 
AE:#1 
 
Concomitant 
XXXXXXXXXXXXXX/ 
XXXXXXXXXXXXX/ 
XXXXXXXXXXXXXXX  
DDMMMYYY (XX)/ 
DDMMMYYY (XX) 
XX/ 
Other: XXXX 
Other: XXX/ 
Unknown 
Prophylaxis 
XXXX-XXX 
Prior 
XXXXXXXXXXXXXX/ 
XXXXXXXXXXXXX/ 
XXXXXXXXXXXXXXX 
DDMMMYYY (XX)/ 
DDMMMYYY (XX) 
XX/  
Tablet 
QAM/ 
Other: XXXX 
Other: XXXXX 
 
 
 
 
 
 
 
Note: Day 1 is the date of first ARV-471/anastrozole dose. Study Day = Assessment Date – Date of Day 1 + 1 for assessment dates on or 
after date of Day 1. Study Day = Assessment Date – Date of Day 1 for assessment prior to Day 1. 
Note: Prior and Concomitant Medications are coded with WHODRUG Global B3 Sep 2022. 
Note: Prior medications include non-study drug medications that are ended before Day 1. Concomitant medications include non-study drug 
medications that are used/started on/after Day 1 and within 30 days from the last administration of the study intervention 
(ie, study drug treatment or surgical resection, whichever occurs last). 
 
Programming Note:  
x Sorting order is by Subject ID, Prior or Concomitant, ATC Category II, Preferred Name 
 
 
 
  
 


Arvinas Estrogen Receptor, Inc (Arvinas) 
 
 
CONFIDENTIAL 
ARV-471-BC-201 
 
<Final 2.0> 
<date> / <time> / <program name> 
 
Page xxx of yyy 
 
126 
Listing 16.2.5.1 
Study Drug Exposure and Compliance  
Analysis Set: Safety Analysis Set 
Treatment: ARV-471 200 mg 
Subject  
ID 
Duration of 
Treatment 
(week) 
Cumulative 
 Dose (mg) 
Absolute Dose 
Intensity 
(mg/week) 
Relative Dose 
Intensity  
(%) 
 
Total Planned 
Dose (mg) 
Compliance  
(%)  
Number  
of Doses 
Interrupted 
Number  
of Doses 
Reduced 
XXXX-XXX 
XX.X 
XX 
XX.X 
XX.X 
XX 
XX.X 
XXX 
XXX 
XXXX-XXX 
XX.X 
XX 
XX.X 
XX.X 
XX 
XX.X 
XXX 
XXX 
XXXX-XXX 
XX.X 
XX 
XX.X 
XX.X 
XX 
XX.X 
XXX 
XXX 
XXXX-XXX 
XX.X 
XX 
XX.X 
XX.X 
XX 
XX.X 
XXX 
XXX 
XXXX-XXX 
XX.X 
XX 
XX.X 
XX.X 
XX 
XX.X 
XXX 
XXX 
XXXX-XXX 
XX.X 
XX 
XX.X 
XX.X 
XX 
XX.X 
XXX 
XXX 
 
 
 
 
 
 
 
 
Note: Duration of treatment (week) is defined as the time from the date of first dose to the date of last dose. 
Cumulative dose (mg) is the sum of ‘Actual total daily dose’ × (End date- Start date+1) per record. Total planned dose 
(mg) is the sum of ‘Planned total daily dose’ × (End date- Start date+1) per record. Compliance is 100*(Cumulative 
dose/Total planned dose), accounting for planned dose modifications and interruptions. Absolute dose intensity 
(mg/week)is (Cumulative Dose (mg))/(Duration of Treatment (week)). Relative dose intesity (%) is (Absolute Dose 
Intensity (mg/week))/(Initial Planned  Weekly Dose (mg/week), 1400 for ARV-471 and 7 for Anastrozole)). 
 
 
 
 
Programming Note:  
x  Sorting order is by Subject ID.  
 
 


Arvinas Estrogen Receptor, Inc (Arvinas) 
 
 
CONFIDENTIAL 
ARV-471-BC-201 
 
<Final 2.0> 
<date> / <time> / <program name> 
 
Page xxx of yyy 
 
127 
Listing 16.2.5.2 
Study Drug Administration  
Analysis Set: Safety Analysis Set 
Actual Treatment: ARV-471 200 mg  
Subject  
ID  
Planned Total 
Daily Dose/Unit 
Route/ 
Frequency  
Start Date 
(Study Day) 
 
End Date 
(Study Day) 
 
Actual 
Total Daily 
Dose/Unit 
 
Action Taken 
Regarding Dose 
Administration? 
 
Reason for Dose 
Adjustment   
XXXX-XXX 
xx/XXXX 
Oral/QD 
DDMMMYYY (XX) DDMMMYYY (XX) 
xx/XXXX 
No action taken  
 
 
xx/XXXX 
Oral/QD 
DDMMMYYY (XX) DDMMMYYY (XX) 
xx/XXXX 
Interrupted 
Other: XXXX 
 
xx/XXXX 
Oral/QD 
DDMMMYYY (XX) DDMMMYYY (XX) 
xx/XXXX 
Discontinued 
AE: #x 
 
xx/XXXX 
Oral/QD 
DDMMMYYY (XX) DDMMMYYY (XX) 
xx/XXXX 
Reduced 
Missed dose 
 
xx/XXXX 
Oral/QD 
DDMMMYYY (XX) DDMMMYYY (XX) 
xx/XXXX 
No action taken  
 
XXXX-XXX 
xx/XXXX 
Oral/QD 
DDMMMYYY (XX) DDMMMYYY (XX) 
xx/XXXX 
Interrupted 
Medication error 
 
xx/XXXX 
Oral/QD 
DDMMMYYY (XX) DDMMMYYY (XX) 
xx/XXXX 
No action taken  
 
 
xx/XXXX 
Oral/QD 
DDMMMYYY (XX) DDMMMYYY (XX) 
xx/XXXX 
No action taken  
 
 
xx/XXXX 
Oral/QD 
DDMMMYYY (XX) DDMMMYYY (XX) 
xx/XXXX 
Increased 
 
 
 
 
 
 
 
 
 
Note: Day 1 is the date of first ARV-471/anastrozole dose. Study Day = Assessment Date – Date of Day 1 + 1 for 
assessment dates on or after date of Day 1. Study Day = Assessment Date – Date of Day 1 for assessment prior to Day 1. 
Note: AE = Adverse Event; Missed dose = Participant missed/Skipped dose.  
 
 
Programming Note:  
x Sorting order is by Subject ID, Start date. 
 


Arvinas Estrogen Receptor, Inc (Arvinas) 
 
 
CONFIDENTIAL 
ARV-471-BC-201 
 
<Final 2.0> 
<date> / <time> / <program name> 
 
Page xxx of yyy 
 
128 
Listing 16.2.5.3 
PK Dosing - ARV-471  
Analysis Set: Safety Analysis Set 
Actual Treatment: ARV-471 200 mg 
Subject  
ID 
Visit 
 
Reference Time 
Point 
     
 
Route/  
Frequency 
Start Date Time  
(Study Day) 
 
Actual 
Dose 
(mg) 
 
Dose Taken 
with Food? 
 
Vomit within 
6 Hours 
After 
Dosing? 
 
Post Dose 
Vomiting Start 
Date Time 
 
XXXX-XXX 
C1D15 
Prior dose 
 
Oral/QD DDMMMYYY HH:MM(XX) 
XXX 
No 
No 
 
 
C2D1 
Prior dose 
 
Oral/QD DDMMMYYY HH:MM(XX) 
XXX 
No 
Yes/AE#XXX 
DDMMMYYY HH:MM 
 
C6D18 
Prior dose 
 
Oral/QD DDMMMYYY HH:MM(XX) 
XXX 
No 
No 
 
XXXX-XXX 
C1D15 
In clinic dose 
 
Oral/QD DDMMMYYY HH:MM(XX) 
XXX 
Yes 
No 
 
 
C2D1 
In clinic dose 
 
Oral/QD DDMMMYYY HH:MM(XX) 
XXX 
No 
Yes/AE#XXXX 
DDMMMYYY HH:MM 
 
C6D18 
In clinic dose 
 
Oral/QD DDMMMYYY HH:MM(XX) 
XXX 
Yes 
No 
 
 
 
 
 
 
 
 
 
 
 
Note: Day 1 is the date of first ARV-471/anastrozole dose. Study Day = Assessment Date – Date of Day 1 + 1 for 
assessment dates on or after date of Day 1. Study Day = Assessment Date – Date of Day 1 for assessment prior to Day 1. 
 
 
 
Programming Note:  
x Sorting order is by Subject ID, Start Date. 


Arvinas Estrogen Receptor, Inc (Arvinas) 
 
 
CONFIDENTIAL 
ARV-471-BC-201 
 
<Final 2.0> 
<date> / <time> / <program name> 
 
Page xxx of yyy 
 
129 
Listing 16.2.5.4 
ARV-471 and ARV-473 Plasma Concentration 
Analysis Set: PK Analysis Set  
Actual Treatment: ARV-471 200 mg 
Subject  
ID 
 
Test (unit) 
 
Visit 
 
Collection Date Time  
(Study Day) 
 
Time Point  
 
Result 
 
Comments 
 
Flag[1] 
 
XXXX-XXX 
ARV-471 (unit) 
C1D15 
DDMMMYYYY HH:MM (XX) Pre-biopsy 
xxx.x 
 
 
 
 
C2D1 
DDMMMYYYY HH:MM (XX) Pre-dose 
xxx.x 
 
a 
 
 
 
DDMMMYYYY HH:MM (XX) 1 hour (± 15 min) post-dose 
xxx.x 
 
 
 
 
 
DDMMMYYYY HH:MM (XX) 2 hours (± 15 min) post-dose 
xxx.x 
XXXXXX 
 
 
 
 
DDMMMYYYY HH:MM (XX) 4 hours (± 30 min) post-dose 
xxx.x 
 
 
 
 
C6D18 
DDMMMYYYY HH:MM (XX) pre-surgery  
xxx.x 
 
c 
 
 
 
 
 
 
 
 
 
ARV-473 (unit) 
 
 
 
 
 
 
XXXX-XXX 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Note: Day 1 is the date of first ARV-471/anastrozole dose. Study Day = Assessment Date – Date of Day 1 + 1 for 
assessment dates on or after date of Day 1. Study Day = Assessment Date – Date of Day 1 for assessment prior to Day 1. 
[1] a: Pre-dose samples are collected after dosing time. b: Post-dose samples are collected out of time window on Cycle 
2 Day 1. c: When ARV-471 dose is different from planned dose.  
 
 
 
Programming Note:  
x Sorting order is by Subject ID, Test , Visit.  
 
 


Arvinas Estrogen Receptor, Inc (Arvinas) 
 
 
CONFIDENTIAL 
ARV-471-BC-201 
 
<Final 2.0> 
<date> / <time> / <program name> 
 
Page xxx of yyy 
 
130 
Listing 16.2.6.1 
Efficacy Parameters – Part 1 of 2  
Analysis Set: Full Analysis Set  
RandomizedTreatment: ARV-471 200 mg  
Subject  
ID 
Ki-67 
Evaluable 
Analysis 
Set 
Actual/Random
iztion Size 
of Primary  
Breast Tumor 
(cm) 
% of Tumor 
cells with Ki67 
Local/Central/R
andomization 
 
Ki-67 Expression 
(%) at Baseline/ 
C1D15/Surgery 
 
Ratio of Ki-67 
between 
C1D15/Surgery  
and Baseline 
Percentage Change 
(%) of Ki-67 at 
C1D15/Surgery  
from Baseline 
mPEPI Score  
at Baseline/ 
after 
Treatment  
Percentage 
Change (%) of 
PR H-score at 
C1D15/Surgery 
from Baseline 
XXXX-XXX 
Yes 
≤2/≤2 
<20%/≥20%/<20% 
XX.X/XX.X/XX.X 
XX.X/XX.X 
XX.X/XX.X 
   >3/0 
XX.X/XX.X 
XXXX-XXX 
Yes 
>2to<5/>2to<5  ≥20%/<20%/<20% XX.X/XX.X/XX.X 
XX.X/XX.X 
XX.X/XX.X 
   1~2/0 
XX.X/XX.X 
XXXX-XXX 
Yes 
≥5/≥5  
<20%/<20%/<20% 
XX.X/XX.X/XX.X 
XX.X/XX.X 
XX.X/XX.X 
   3/1~2 
XX.X/XX.X 
XXXX-XXX 
Yes 
≤2/≤2  
 ≥20%/≥20%/≥20% XX.X/XX.X/XX.X 
XX.X/XX.X 
XX.X/XX.X 
   >3/1~2 
XX.X/XX.X 
XXXX-XXX 
Yes 
>2to<5  
≥20%/≥20%/≥20% 
XX.X/XX.X/XX.X 
XX.X/XX.X 
XX.X/XX.X 
   0/0 
XX.X/XX.X 
XXXX-XXX 
Yes 
≥5/>2to<5   ≥20%/≥20%/≥20% XX.X/XX.X/XX.X 
XX.X/XX.X 
XX.X/XX.X 
   1~2/0 
XX.X/XX.X 
XXXX-XXX 
Yes 
≤2/≤2  
<20%/<20%/<20% 
XX.X/XX.X/XX.X 
XX.X/XX.X 
XX.X/XX.X 
   3/0 
XX.X/XX.X 
XXXX-XXX 
No 
>2to<5/≥5   ≥20%/≥20%/≥20% XX.X/XX.X/XX.X 
XX.X/XX.X 
XX.X/XX.X 
   >3/1~2 
XX.X/XX.X 
 
 
 
 
 
 
 
 
Note: mPEPI = Modified Pre-operative Endocrine Prognostic Index.   
Note: Ratio of Ki-67 between C1D15/Surgery and baseline = log(Ki-67 at C1D15/Surgery)-log(Ki-67 at baseline), the 
variable for the primary endpoint.   
Note: Ki-67 Percentage Change from Baseline at C1D15/Surgery = 100 ×(Ki-67 at C1D15/Surgery - Ki-67 at baseline)/Ki-67 at 
baseline. 
  
 
Programming Note:  
x 
Sorting order is by Subject ID.   
 
 
 


Arvinas Estrogen Receptor, Inc (Arvinas) 
 
 
CONFIDENTIAL 
ARV-471-BC-201 
 
<Final 2.0> 
<date> / <time> / <program name> 
 
Page xxx of yyy 
 
131 
Listing 16.2.6.2 
Efficacy Parameters – Part 2 of 2 
Analysis Set: Full Analysis Set 
RandomizedTreatment: ARV-471 200 mg  
Subject 
ID 
Ki-67 
Evaluable 
Analysis 
Set 
Actual/Random
iztion Size 
of Primary 
Breast Tumor 
% of Tumor cells 
with Ki67 
Local/Central/Ra
ndomization 
Post-Surgery 
Pathological 
Response/Derived 
Response  
Breast 
Conserving 
Surger 
Caliper 
Based Best 
Percentage 
Change from 
Baseline (%) 
Complete 
Cycle Cell 
Arrest at 
Week 
2/Surgery 
Percentage 
Change (%) of ER 
AQUA score at 
C1D15/Surgery 
from Baseline  
XXXX-XXX 
Yes 
≤2/≤2 
<20%/≥20%/<20%  
pCR/pCR  
Yes 
xx.x 
Yes/Yes 
XX.X/XX.X 
XXXX-XXX 
Yes 
>2to<5/>2to<5  ≥20%/<20%/<20% 
pPR/non-pCR 
No 
xx.x 
Yes/Yes 
XX.X/XX.X 
XXXX-XXX 
Yes 
≥5/≥5  
<20%/<20%/<20% 
pPR/pCR 
Yes 
xx.x 
No/Yes 
XX.X/XX.X 
XXXX-XXX 
Yes 
≤2/≤2  
 ≥20%/≥20%/≥20% 
pCR/pCR  
Yes 
xx.x 
Yes/No 
XX.X/XX.X 
XXXX-XXX 
Yes 
>2to<5  
≥20%/≥20%/≥20%  
pPR/non-pCR 
Yes 
xx.x 
Yes/Yes 
XX.X/XX.X 
XXXX-XXX 
Yes 
≥5/>2to<5   ≥20%/≥20%/≥20% 
pPR/non-pCR 
Yes 
xx.x 
No/Yes 
XX.X/XX.X 
XXXX-XXX 
Yes 
≤2/≤2  
<20%/<20%/<20%  
pCR/non-pCR 
No 
xx.x 
Yes/Yes 
XX.X/XX.X 
XXXX-XXX 
No 
>2to<5/≥5   ≥20%/≥20%/≥20% 
NR/non-pCR 
Yes 
xx.x 
Yes/Yes 
XX.X/XX.X 
 
 
 
 
 
 
 
 
Note: pCR = Pathological Complete Response.   
Note: Complete cycle cell arrest at Week 2/Surgery is defined as Ki67 score ≤ 2.7%.   
Note: Percentage Change (%) of ER at C1D15/Surgery from Baseline 100 × (ER AQUA at C1D15/surgery – ER AQUA at 
baseline)/ER AQUA at baseline. 
 
 
Programming Note:  
x 
Sorting order is by Subject ID.   
 
 


Arvinas Estrogen Receptor, Inc (Arvinas) 
 
 
CONFIDENTIAL 
ARV-471-BC-201 
 
<Final 2.0> 
<date> / <time> / <program name> 
 
Page xxx of yyy 
 
132 
Listing 16.2.6.3 Target Lesion (TL)  
Analysis Set: Full Analysis Set  
Randomized Treatment: ARV-471 200 mg  
Subject  
ID  
Baseline 
Tumor Size  
Assessment 
Timepoint  
Date of 
Assessment  
(Study Day)  
Sum of TL  
(mm)  
% Change from 
Baseline of TL 
Sum of Primary 
Tumor TL  
(mm)  
% Change from 
Baseline of 
Primary Tunor TL 
XXXX-XXX 
≤2 cm 
Screen 
DDMMMYYY (XX) 
XXX 
 
XXX 
 
 
 
Cycle 1 
DDMMMYYY (XX) 
XXX 
XX.X 
XXX 
XX.X 
 
 
Cycle 2 
DDMMMYYY (XX) 
XXX 
XX.X 
XXX 
XX.X* 
 
 
Cycle 3 
DDMMMYYY (XX) 
XXX 
XX.X 
XXX 
XX.X 
 
 
Cycle 4 
DDMMMYYY (XX) 
XXX 
XX.X* 
XXX 
XX.X 
 
 
Cycle 5 
DDMMMYYY (XX) 
XXX 
XX.X 
XXX 
XX.X 
 
 
Cycle 6 
DDMMMYYY (XX) 
XXX 
XX.X 
XXX 
XX.X 
XXXX-XXX 
≤2 cm 
Screen 
DDMMMYYY (XX) 
XXX 
 
XXX 
 
 
 
Cycle 1 
DDMMMYYY (XX) 
XXX 
XX.X 
XXX 
XX.X 
 
 
Cycle 2 
DDMMMYYY (XX) 
XXX 
XX.X 
XXX 
XX.X 
 
 
Cycle 3 
DDMMMYYY (XX) 
XXX 
XX.X 
XXX 
XX.X* 
 
 
Cycle 4 
DDMMMYYY (XX) 
XXX 
XX.X* 
XXX 
XX.X 
 
 
 
 
 
 
 
 
Note: Day 1 is the date of first ARV-471/anastrozole dose. Study Day = Assessment Date – Date of Day 1 + 1 for 
assessment dates on or after date of Day 1. Study Day = Assessment Date – Date of Day 1 for assessment prior to Day 1. 
Note: Best percentage change of TL from baseline (indicated with *) is maximum decrease or minimum increase if no 
decrease being observed. 
 
 
Programming Note:  
x Sorting order is by Subject ID, Date of Assessment 
 
 
 


Arvinas Estrogen Receptor, Inc (Arvinas) 
 
 
CONFIDENTIAL 
ARV-471-BC-201 
 
<Final 2.0> 
<date> / <time> / <program name> 
 
Page xxx of yyy 
 
133 
Listing 16.2.6.4 Primary Breast Tumor Change - Caliper-based  
Analysis Set: Full Analysis Set  
Randomized Treatment: ARV-471 200 mg  
Subject  
ID  
Baseline 
Tumor Size  
Assessment Timepoint  
Date of Assessment 
(Study Day)  
 
Primary Breast 
Tumor (mm)  
 
% Change  
from Baseline    
Best % Change 
from Baseline ? 
 
XXXX-XXX 
≤2 cm 
Screen 
DDMMMYYY (XX) 
XXX 
 
 
 
 
Cycle 1 
DDMMMYYY (XX) 
XXX 
XX.X 
 
 
 
Cycle 2 
DDMMMYYY (XX) 
XXX 
XX.X 
 
 
 
Cycle 3 
DDMMMYYY (XX) 
XXX 
XX.X 
 
 
 
Cycle 4 
DDMMMYYY (XX) 
XXX 
XX.X 
Yes 
 
 
Cycle 5 
DDMMMYYY (XX) 
XXX 
XX.X 
 
 
 
Cycle 6 
DDMMMYYY (XX) 
XXX 
XX.X 
 
XXXX-XXX 
≤2 cm 
Screen 
DDMMMYYY (XX) 
XXX 
 
 
 
 
Cycle 1 
DDMMMYYY (XX) 
XXX 
XX.X 
 
 
 
Cycle 2 
DDMMMYYY (XX) 
XXX 
XX.X 
 
 
 
Cycle 3 
DDMMMYYY (XX) 
XXX 
XX.X 
 
 
 
Cycle 4 
DDMMMYYY (XX) 
XXX 
XX.X 
Yes 
 
 
 
 
 
 
 
Note: Day 1 is the date of first ARV-471/anastrozole dose. Study Day = Assessment Date – Date of Day 1 + 1 for 
assessment dates on or after date of Day 1. Study Day = Assessment Date – Date of Day 1 for assessment prior to Day 1. 
Note: Best percentage change from baseline is maximum decrease or minimum increase if no decrease being observed. 
 
 
Programming Note:  
x Sorting order is by Subject ID, Date of Assessment 


Arvinas Estrogen Receptor, Inc (Arvinas) 
 
 
CONFIDENTIAL 
ARV-471-BC-201 
 
<Final 2.0> 
<date> / <time> / <program name> 
 
Page xxx of yyy 
 
134 
Listing 16.2.6.5 Tumor Biopsy  
Analysis Set: Full Analysis Set  
Randomized Treatment: ARV-471 200 mg  
Subject  
ID  
Test (SI unit)  
Visit  
Collection Date  
(Study Day)     
Result/ 
% Change from 
Baseline  
Interpretation 
Location/ 
Method 
XXXX-XXX 
Ki-67 (%)  
Screening 
DDMMMYYYY (XX) 
XX.X* 
Positive 
Breast/IHC 
 
 
C1D15 
DDMMMYYYY (XX) 
XX.X/XX.X 
Intermediate Proliferation Rate 
Breast/IHC 
 
 
C6D18 
DDMMMYYYY (XX) 
XX.X/XX.X 
High Proliferation Rate 
Unknown/IHC 
 
<Insert (XXX)> 
Screening 
DDMMMYYYY (XX) 
XX.X* 
High Proliferation Rate 
Breast/IHC 
 
 
C1D15 
DDMMMYYYY (XX) 
XX.X/XX.X 
Intermediate Proliferation Rate 
Breast/IHC 
 
 
C6D18 
DDMMMYYYY (XX) 
XX.X/XX.X 
Positive 
Breast/IHC 
 
 
Unscheduled 
DDMMMYYYY (XX) 
XX.X/XX.X 
Positive 
Breast/IHC 
XXXX-XXX 
Ki-67 (%)  
Screening 
DDMMMYYYY (XX) 
XX.X* 
High Proliferation Rate 
Other:XX/IHC 
 
 
C1D15 
DDMMMYYYY (XX) 
Uninterpretable 
Uninterpretable 
Breast/IHC 
 
 
C6D18 
DDMMMYYYY (XX) 
XX.X/XX.X 
Positive 
Breast/IHC 
 
 
Unscheduled 
DDMMMYYYY (XX) 
XX.X/XX.X 
Positive 
Breast/IHC 
 
 
 
 
 
 
 
Note: Day 1 is the date of first ARV-471/anastrozole dose. Study Day = Assessment Date – Date of Day 1 + 1 for 
assessment dates on or after date of Day 1. Study Day = Assessment Date – Date of Day 1 for assessment prior to Day 1. 
Note: IHC = Immunohistochemistry. 
Note: * indicates baseline value. 
 
 
 
Programming Note:  
x Sorting order is by Subject ID, Test, Collection date 
 
 
 


Arvinas Estrogen Receptor, Inc (Arvinas) 
 
 
CONFIDENTIAL 
ARV-471-BC-201 
 
<Final 2.0> 
<date> / <time> / <program name> 
 
Page xxx of yyy 
 
135 
Listing 16.2.6.6 Imaging Response Assessment - mRECIST  
Analysis Set: Full Analysis Set 
Randomized Treatment: ARV-471 200 mg  
Subject  
ID  
Assessment 
Timepoint  
Date of Assessment 
(Study Day)  
Target Lesion  
Response  
Non-Target Lesion 
Response  
Any New 
Lesions?  
Response at this 
Timepoint 
XXXX-XXX Cycle 1 
DDMMMYYY (XX) 
Partial Response 
Non-CR/Non-PD 
No 
Partial Response 
 
Cycle 2 
DDMMMYYY (XX) 
Partial Response 
Non-CR/Non-PD 
No 
Partial Response 
 
Cycle 3 
DDMMMYYY (XX) 
Partial Response 
Non-CR/Non-PD 
No 
Partial Response 
 
Cycle 4 
DDMMMYYY (XX) 
Partial Response 
Non-CR/Non-PD 
Yes 
Progressive Disease 
 
Cycle 5 
DDMMMYYY (XX) 
Progressive Disease 
Not Evaluable 
Yes 
Progressive Disease 
 
Pre-Surgery 
DDMMMYYY (XX) 
 
 
 
 
XXXX-XXX Cycle 1 
DDMMMYYY (XX) 
Stable Disease 
Not Evaluable 
No 
Stable Disease 
 
Cycle 2 
DDMMMYYY (XX) 
Stable Disease 
Not Evaluable 
No 
Stable Disease 
 
Cycle 3 
DDMMMYYY (XX) 
Not Evaluable 
Complete Response 
No 
Not Evaluable 
 
Cycle 4 
DDMMMYYY (XX) 
Complete Response 
Complete Response 
No 
Complete Response 
 
 
 
 
 
 
 
Note: Day 1 is the date of first ARV-471/anastrozole dose. Study Day = Assessment Date – Date of Day 1 + 1 for 
assessment dates on or after date of Day 1. Study Day = Assessment Date – Date of Day 1 for assessment prior to Day 1. 
 
 
Programming Note:  
x Sorting order is by Subject ID, Date of Procedure 
 
 
 
 


Arvinas Estrogen Receptor, Inc (Arvinas) 
 
 
CONFIDENTIAL 
ARV-471-BC-201 
 
<Final 2.0> 
<date> / <time> / <program name> 
 
Page xxx of yyy 
 
136 
Listing 16.2.6.7 Cytology Results  
Analysis Set: Full Analysis Set 
Randomized Treatment: ARV-471 200 mg  
Subject  
ID  
Date Sample  
Collected (Study Day)  
Specimen Type   
Findings   
XXXX-XXX 
DDMMMYYY (XX) 
Pleural Effusion  
Benign  
 
DDMMMYYY (XX) 
Abdominal/Pelvic Ascites 
Atypical 
XXXX-XXX 
DDMMMYYY (XX) 
Other: XXXXXXXXX 
Suspicious 
 
DDMMMYYY (XX) 
DDMMMYYY (XX) 
Malignant 
XXXX-XXX 
DDMMMYYY (XX) 
DDMMMYYY (XX) 
Other: XXXXXXX 
 
DDMMMYYY (XX) 
DDMMMYYY (XX) 
Benign  
 
DDMMMYYY (XX) 
DDMMMYYY (XX) 
Atypical 
 
 
 
 
Note: Day 1 is the date of first ARV-471/anastrozole dose. Study Day = Assessment Date – Date of Day 1 + 1 for 
assessment dates on or after date of Day 1. Study Day = Assessment Date – Date of Day 1 for assessment prior to Day 1. 
 
 
Programming Note:  
x Sorting order is by Subject ID, Date Sample Collected 
 
 


Arvinas Estrogen Receptor, Inc (Arvinas) 
 
 
CONFIDENTIAL 
ARV-471-BC-201 
 
<Final 2.0> 
<date> / <time> / <program name> 
 
Page xxx of yyy 
 
137 
Listing 16.2.6.8 Disease Staging - Post-Surgery  
Analysis Set: Full Analysis Set 
Randomized Treatment: ARV-471 200 mg  
Subject  
ID  
Ki-67 
Evaluable 
Analysis Set 
Date of Tumor  
Tissue Collected  
(Study Day)  
Pathologic  
Tumor - ypT  
Multiple Foci 
of Residual 
Tumor?  
Pathologic 
Lymph Nodes - 
ypN 
Distant 
Metastasis ypT 
Lymphatic 
Vascular Invasion 
Classification 
  
XXXX-XXX 
Yes 
DDMMMYYY (XX) 
ypTx  
No 
ypNX  
M0  
Present  
XXXX-XXX 
Yes 
DDMMMYYY (XX) 
ypT0 
No 
ypN0 
pM1 
Not Present 
XXXX-XXX 
Yes 
DDMMMYYY (XX) 
ypTis 
No 
ypN0(i+) 
Unknown 
Unknown 
XXXX-XXX 
Yes 
DDMMMYYY (XX) 
ypT1mi 
Yes 
ypN0(mol+) 
M0  
Not Present 
XXXX-XXX 
Yes 
DDMMMYYY (XX) 
ypT1a 
Yes 
ypN1 
M0  
Not Present 
XXXX-XXX 
Yes 
DDMMMYYY (XX) 
ypT1b 
Yes 
ypN1mi 
M0  
Not Present 
XXXX-XXX 
Yes 
DDMMMYYY (XX) 
ypT1c 
No 
ypN1a 
M0  
Not Present 
XXXX-XXX 
No 
DDMMMYYY (XX) 
ypT2 
No 
ypN1b 
Unknown 
Not Present 
 
 
 
 
 
 
 
 
Note: Day 1 is the date of first ARV-471/anastrozole dose. Study Day = Assessment Date – Date of Day 1 + 1 for 
assessment dates on or after date of Day 1. Study Day = Assessment Date – Date of Day 1 for assessment prior to Day 1. 
 
 
Programming Note:  
x Sorting order is by Subject ID, Date of Procedure 
 
 
 


Arvinas Estrogen Receptor, Inc (Arvinas) 
 
 
CONFIDENTIAL 
ARV-471-BC-201 
 
<Final 2.0> 
<date> / <time> / <program name> 
 
Page xxx of yyy 
 
138 
Listing 16.2.7.1 
Adverse Events by Subject  
Analysis Set: Safety Analysis Set  
Actual Treatment: ARV-471 200 mg  
Subject  
ID  
System Organ Class/  
Preferred Term/  
Verbatim 
Start Date  
(StudyDay)/ 
Stop Date   
(StudyDay)/ 
TEAE?  
Serious?/ 
Toxicity  
Grade/ 
Lead to Study 
Discontinued 
Relation to  
Study Drug/  
Action Taken  
with Study Drug 
Related to 
Concomitant 
Medication? 
 / 
Specify 
Outcome/ 
Concomitant 
Medication Given/ 
Non-drug  
Treatment Given? 
XXXX-XXX 
XXXXXXXXXXXXXXXXXXXXX/ 
XXXXXXXXXXXXXXXXXXX/ 
XXXXXXXXXXXXXXXXXXXXXX 
DDMMMYYY (xx)/ 
Ongoing/ 
No 
No/ 
2/ 
No 
Not Related/  
Dose Not Changed 
No 
RED/ 
No/ 
Yes 
 
 
 
 
 
 
 
 
XXXXXXXXXXXXXXXXXXXXX/ 
XXXXXXXXXXXXXXXXXXX/ 
XXXXXXXXXXXXXXXXXXXXXX 
DDMMMYYY (xx)/ 
Ongoing/ 
 Yes 
Yes/ 
4/ 
No 
Related/ 
Dose Reduced 
 
NRED/ 
Yes/ 
No 
 
 
 
 
 
 
XXXX-XXX 
XXXXXXXXXXXXXXXXXXXXX/ 
XXXXXXXXXXXXXXXXXXX/ 
XXXXXXXXXXXXXXXXXXXXXX 
DDMMMYYY (xx)/ 
DDMMMYYY(xx)/ 
 Yes 
Yes/ 
1/ 
No 
Not Related / 
Drug Withdrawn 
Yes/ 
XXXX,XXXXX 
REDWSEQ/ 
No/ 
No 
 
 
 
 
 
 
 
 
XXXXXXXXXXXXXXXXXXXXX/ 
XXXXXXXXXXXXXXXXXXX/ 
XXXXXXXXXXXXXXXXXXXXXX 
DDMMMYYY (xx)/ 
DDMMMYYY (xx)/ 
Yes 
No/ 
5/ 
Yes 
Not Related / 
Not Applicable 
No 
Fatal/ 
Yes/ 
Yes 
 
 
 
 
 
 
 
 
Note: Day 1 is the date of first ARV-471/anastrozole dose. Study Day = Assessment Date – Date of Day 1 + 1 for 
assessment dates on or after date of Day 1. Study Day = Assessment Date – Date of Day 1 for assessment prior to Day 1. 
Note: Adverse events (AE) were evaluated based on NCI-CTCAE (version 5.0),and coded with MedDRA Version 24.1. 
Note: A TEAE is an AE that emerges or worsens (ie increase in CTCAE grade) on/after the first dose of ARV-
471/Anastrozole to 30 days from the last administration of the study intervention (ie, study drug treatment or surgical resection, 
whichever occurs last). 
Note: RED=Recovered/Resolved; NRED=Not Recovered/Not Resolved; REDWSEQ=Recovered/Resolved with Sequelae; REING= 
Recovering/Resolving. 
 
 
Programming Note:  
x Sorting order is by Subject ID, Start Date, System Organ Class and Preferred Term.  
 
Listing 16.2.7.2 
Serious Adverse Events by Subject  
Analysis Set: Safety Analysis Set  
Actual Treatment: ARV-471 200 mg  


Arvinas Estrogen Receptor, Inc (Arvinas) 
 
 
CONFIDENTIAL 
ARV-471-BC-201 
 
<Final 2.0> 
<date> / <time> / <program name> 
 
Page xxx of yyy 
 
139 
Subject  
ID Age/Race/ 
Sex  
System Organ Class/  
Preferred Term/  
Verbatim 
Start Date  
(StudyDay)/ 
Stop Date   
(StudyDay)/ 
TEAE?  
Serious?/ 
Toxicity  
Grade/ 
Lead to Study 
Discontinued 
Relation to  
Study Drug/  
Action Taken  
with Study Drug 
Related to 
Concomitant 
Medication?/ 
Specify 
Outcome/ 
Concomitant 
Medication Given/ 
Non-drug  
Treatment Given? 
XXXX-XXX/ 
XX/W/F 
XXXXXXXXXXXXXXXXXXXXX/ 
XXXXXXXXXXXXXXXXXXX/ 
XXXXXXXXXXXXXXXXXXXXXX 
DDMMMYYY (xx)/ 
Ongoing/ 
No 
Yes/ 
2/ 
No 
Not Related/  
Dose Not Changed 
No 
RED/ 
No/ 
Yes 
 
 
 
 
 
 
 
 
XXXXXXXXXXXXXXXXXXXXX/ 
XXXXXXXXXXXXXXXXXXX/ 
XXXXXXXXXXXXXXXXXXXXXX 
DDMMMYYY (xx)/ 
Ongoing/ 
 Yes 
Yes/ 
4/ 
No 
Related/ 
Dose Reduced 
 
NRED/ 
Yes/ 
No 
 
 
 
 
 
 
XXXX-XXX/ 
XX/B/M 
XXXXXXXXXXXXXXXXXXXXX/ 
XXXXXXXXXXXXXXXXXXX/ 
XXXXXXXXXXXXXXXXXXXXXX 
DDMMMYYY (xx)/ 
DDMMMYYY(xx)/ 
 Yes 
Yes/ 
1/ 
No 
Not Related / 
Drug Withdrawn 
Yes/ 
XXXX,XXXXX 
REDWSEQ/ 
No/ 
No 
 
 
 
 
 
 
 
 
XXXXXXXXXXXXXXXXXXXXX/ 
XXXXXXXXXXXXXXXXXXX/ 
XXXXXXXXXXXXXXXXXXXXXX 
DDMMMYYY (xx)/ 
DDMMMYYY (xx)/ 
Yes 
Yes/ 
5/ 
Yes 
Not Related / 
Not Applicable 
No 
Fatal/ 
Yes/ 
Yes 
 
 
 
 
 
 
 
 
Note: Day 1 is the date of first ARV-471/anastrozole dose. Study Day = Assessment Date – Date of Day 1 + 1 for 
assessment dates on or after date of Day 1. Study Day = Assessment Date – Date of Day 1 for assessment prior to Day 1. 
Note: Adverse events (AE) were evaluated based on NCI-CTCAE (version 5.0),and coded with MedDRA Version 24.1. 
Note: A TEAE is an AE that emerges or worsens (ie increase in CTCAE grade) on/after the first dose of ARV-
471/Anastrozole to 30 days from the last administration of the study intervention (ie, study drug treatment or surgical resection, 
whichever occurs last). 
Note: RED=Recovered/Resolved; NRED=Not Recovered/Not Resolved; REDWSEQ=Recovered/Resolved with Sequelae; REING= 
Recovering/Resolving.  
Note: N = American Indian or Alaskan Native; A = Asian; B = Black or African American; H = Native Hawaiian or Other 
Pacific Islander; W= White; NR = Not Reported; O= Other; M = Male; F = Female. 
 
 
 
Programming Note:  
x Sorting order is by Subject ID, Start Date, System Organ Class and Preferred Term.  
Subject ID/Age/Race/Sex, Preferred Term, Treatment Arm, Onset Day, Grade, Investigator-Assessed Relatedness 
Display order by treatment arm ARV-471 200mg first, then follow by Anastrozole 1mg 
 


Arvinas Estrogen Receptor, Inc (Arvinas) 
 
 
CONFIDENTIAL 
ARV-471-BC-201 
 
<Final 2.0> 
<date> / <time> / <program name> 
 
Page xxx of yyy 
 
140 
Listing 16.2.8.1 
Hematology Tests with CTCAE Grade ≥ 3 
Analysis Set: Safety Analysis Set  
Actual Treatment: ARV-471 200 mg  
Subject  
ID  
Test (SI unit)  
Visit  
Collection Date Time  
(Study Day)     
Result/ 
Change from Baseline/ 
% Change from Baseline  
Reference 
Range 
 
Reference 
Range 
Indicator 
 
CTCAE 
Grade 
 
XXXX-XXX 
Hemoglobin (g/L)  
Screening 
DDMMMYYYY HH:MM (XX) 
XX.X 
XXX,XXX 
Low 
1 
 
 
C1D1 
DDMMMYYYY HH:MM (XX) 
XX.X* 
XXX,XXX 
Normal 
0 
 
 
C1D8 
DDMMMYYYY HH:MM (XX) 
XX.X/XX.X/XX.X 
XXX,XXX 
High 
2 
 
 
<insert> 
 
 
 
 
 
 
<insert> 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
XXXX-XXX 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Note: Day 1 is the date of first ARV-471/anastrozole dose. Study Day = Assessment Date – Date of Day 1 + 1 for 
assessment dates on or after date of Day 1. Study Day = Assessment Date – Date of Day 1 for assessment prior to Day 1. 
Note: Lab data is graded with CTCAE version 5.0. 
Note: * indicates baseline value. 
 
 
Programming Note:  
x Sorting order is by Subject ID, Test, Collection date  
x if a subject has a test with CTCAE grade>=3, all visits of the test will be listed. 
 
 
 
 
Programming note: Repeat Listing 16.2.8.1 for the following listings 
 
Listing 16.2.8.2 Clinical Chemistry Tests with CTCAE Grade ≥ 3  
Analysis Set: Safety Analysis Set  
 
 
 
 
 
 


Arvinas Estrogen Receptor, Inc (Arvinas) 
 
 
CONFIDENTIAL 
ARV-471-BC-201 
 
<Final 2.0> 
<date> / <time> / <program name> 
 
Page xxx of yyy 
 
141 
Listing 16.2.8.3 
Hematology Tests  
Analysis Set: Safety Analysis Set  
Actual Treatment: ARV-471 200 mg  
Subject  
ID  
Test (SI unit)  
Visit  
Collection 
Date(Study Day) 
Result/  
Change from Baselin/ 
Reference 
Range  
Reference 
Range 
Indicator  
CTCAE 
Grade  
 XXXX-XXX 
Hemoglobin (g/L)  
Screening 
DDMMMYYYY (XX) 
XX.X 
XXX,XXX 
Low 
1 
 
 
C1D1 
DDMMMYYYY (XX) 
XX.X* 
XXX,XXX 
Normal 
0 
 
 
C1D8 
DDMMMYYYY (XX) 
XX.X/XX.X 
XXX,XXX 
High 
2 
 
 
<insert> 
 
 
 
 
 
 
<insert> 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
XXXX-XXX 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Note: Day 1 is the date of first ARV-471/anastrozole dose. Study Day = Assessment Date – Date of Day 1 + 1 for 
assessment dates on or after date of Day 1. Study Day = Assessment Date – Date of Day 1 for assessment prior to Day 1. 
Note: Lab data is graded with CTCAE version 5.0. 
Note: * indicates baseline value. 
 
Programming Note:  
x Sorting order is by Subject ID, Test, Collection date  
 
Programming note: Repeat Listing 16.2.8.3 for the following listings 
 
Listing 16.2.8.4 
Clinical Chemistry Tests  
Analysis Set: Safety Analysis Set  
 
 
Listing 16.2.8.5 
Coagulation Tests   
Analysis Set: Safety Analysis Set  
 
 
 


Arvinas Estrogen Receptor, Inc (Arvinas) 
 
 
CONFIDENTIAL 
ARV-471-BC-201 
 
<Final 2.0> 
<date> / <time> / <program name> 
 
Page xxx of yyy 
 
142 
Listing 16.2.8.6 
Urinalysis  
Analysis Set: Safety Analysis Set  
Actual Treatment: ARV-471 200 mg  
Subject  
ID  
Test  
 
Visit  
Collection Date  
(Study Day)  
Result  
(unit, if applicable)  
XXXX-XXX 
Clarity 
 
Screening 
DDMMMYYYY (XX) 
Trace 
 
 
 
C1D1 
DDMMMYYYY (XX) 
1+* 
 
 
 
C1D8 
DDMMMYYYY (XX) 
2+ 
 
 
 
<insert> 
 
 
 
<insert> 
 
 
 
 
 
 
 
 
 
 
XXXX-XXX 
 
 
 
 
 
 
 
 
 
 
 
Note: Day 1 is the date of first ARV-471/anastrozole dose. Study Day = Assessment Date – Date of Day 1 + 1 for 
assessment dates on or after date of Day 1. Study Day = Assessment Date – Date of Day 1 for assessment prior to Day 1. 
Note: * indicates baseline value. 
 
 
Programming Note:  
x 
Sorting order is by Subject ID, Test, Visit.  
  
 


Arvinas Estrogen Receptor, Inc (Arvinas) 
 
 
CONFIDENTIAL 
ARV-471-BC-201 
 
<Final 2.0> 
<date> / <time> / <program name> 
 
Page xxx of yyy 
 
143 
Listing 16.2.9 
Vital Signs 
Analysis Set: Safety Analysis Set  
Actual Treatment: ARV-471 200 mg  
Subject  
ID  
Test (SI unit)  
Visit  
Vital Signs Date   
(Study Day)  
Result/  
Change from Baseline  
XXXX-XXX 
Diastolic Blood Pressure (mmHg) 
Screening 
DDMMMYYYY (XX) 
XX.X 
 
 
C1D1 
DDMMMYYYY (XX) 
XX.X* 
 
 
C1D8 
DDMMMYYYY (XX) 
XX.X/XX.X 
 
 
<insert> 
 
 
 
<insert> 
 
 
 
 
 
 
 
 
XXXX-XXX 
 
 
 
 
 
 
 
 
 
Note: Day 1 is the date of first ARV-471/anastrozole dose. Study Day = Assessment Date – Date of Day 1 + 1 for 
assessment dates on or after date of Day 1. Study Day = Assessment Date – Date of Day 1 for assessment prior to Day 1. 
Note: * indicates baseline value. 
 
 
Programming Note:  
x Sorting order is by Subject ID, Test, Visit.  
x If Clinical provides a list of any parameter deemed significant, list the parameter of all visits of  the patient 
 


Arvinas Estrogen Receptor, Inc (Arvinas) 
 
 
CONFIDENTIAL 
ARV-471-BC-201 
 
<Final 2.0> 
<date> / <time> / <program name> 
 
Page xxx of yyy 
 
144 
Listing 16.2.10 
12-Lead ECG  
Analysis Set: Safety Analysis Set  
Actual Treatment: ARV-471 200 mg  
Subject  
ID  
Test (unit)  
 
Visit  
 
ECG Date Time  
(Study Day) 
 
Time Point  
 
Test  
Number 
 
Result 
  
XXXX-XXX 
Heart Rate (beats per minute) 
Screening 
DDMMMYYYY HH:MM (XX) 
Screening 
 
xxx.x 
 
 
C1D1 
DDMMMYYYY HH:MM (XX) 
Predose  
1 
xxx.x 
 
 
 
DDMMMYYYY HH:MM (XX) 
Predose  
2 
xxx.x 
 
 
 
DDMMMYYYY HH:MM (XX) 
Predose  
3 
xxx.x 
 
 
 
DDMMMYYYY HH:MM (XX) 4hr post dose 
1 
xxx.x 
 
 
 
DDMMMYYYY HH:MM (XX) 4hr post dose 
2 
xxx.x 
 
 
 
DDMMMYYYY HH:MM (XX) 4hr post dose 
3 
xxx.x 
 
 
C1D8 
DDMMMYYYY HH:MM (XX) 
Predose  
1 
xxx.x 
 
 
 
DDMMMYYYY HH:MM (XX) 
Predose  
2 
xxx.x 
 
 
<insert> 
 
 
 
 
 
 
 
 
 
 
 
XXXX-XXX 
 
 
 
 
 
 
 
 
 
 
 
 
 
Note: Day 1 is the date of first ARV-471/anastrozole dose. Study Day = Assessment Date – Date of Day 1 + 1 for 
assessment dates on or after date of Day 1. Study Day = Assessment Date – Date of Day 1 for assessment prior to Day 1. 
 
 
 
Programming Note:  
x Sorting order is by Subject ID, Test , Visit.  


Arvinas Estrogen Receptor, Inc (Arvinas) 
 
 
CONFIDENTIAL 
ARV-471-BC-201 
 
<Final 2.0> 
<date> / <time> / <program name> 
 
Page xxx of yyy 
 
145 
Listing 16.2.11 
ECOG Performance Status   
Analysis Set: Safety Analysis Set  
Actual Treatment: ARV-471 200 mg  
Subject  
ID   
ECOG Performance Status 
performed? 
 
Visit  
ECOG Assessment Date  
(Study Day)  
ECOG Performance 
Status     
XXXX-XXX 
Yes 
Screening 
DDMMMYYYY (XX) 
0 
 
Yes 
C1D1* 
DDMMMYYYY (XX) 
0 
 
Yes 
C1D8 
 
 
 
Yes 
<insert> 
 
 
 
 
 
 
 
XXXX-XXX 
No 
 
 
 
 
 
 
 
 
Note: Day 1 is the date of first ARV-471/anastrozole dose. Study Day = Assessment Date – Date of Day 1 + 1 for 
assessment dates on or after date of Day 1. Study Day = Assessment Date – Date of Day 1 for assessment prior to Day 1. 
Note: * indicates baseline value. 
 
Programming Note:  
x Sorting order is by Subject ID, Visit.  




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