History of Changes for Study: NCT05654623

A Study to Learn About a New Medicine Called ARV-471 (PF-07850327) in People Who Have Advanced Metastatic Breast Cancer. (VERITAC-2)

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Study Record Versions

Version	Submitted Date	Changes
1	December 8, 2022	None (earliest Version on record)
2	December 29, 2022	Study Status, Study Identification, Contacts/Locations and Study Design
3	January 27, 2023	Recruitment Status, Study Status, Contacts/Locations and Oversight
4	February 5, 2023	Contacts/Locations and Study Status
5	March 13, 2023	Study Status and Contacts/Locations
6	April 12, 2023	Contacts/Locations and Study Status
7	May 31, 2023	Contacts/Locations and Study Status
8	June 21, 2023	Contacts/Locations and Study Status
9	July 20, 2023	Contacts/Locations, Study Status, Eligibility, Conditions and Study Description
10	August 15, 2023	Contacts/Locations and Study Status
11	September 8, 2023	Contacts/Locations and Study Status
12	September 19, 2023	Contacts/Locations, References and Study Status
13	February 13, 2024	Contacts/Locations and Study Status
14	April 23, 2024	Study Status

Comparison Format:

Merged
Side-by-Side

Study Identification


Unique Protocol ID:	C4891001
Brief Title:	A Study to Learn About a New Medicine Called ARV-471 (PF-07850327) in People Who Have Advanced Metastatic Breast Cancer. (VERITAC-2)
Official Title:	A PHASE 3, RANDOMIZED, OPEN-LABEL, MULTICENTER TRIAL OF ARV-471 (PF-07850327) VS FULVESTRANT IN PARTICIPANTS WITH ESTROGEN RECEPTOR-POSITIVE, HER2-NEGATIVE ADVANCED BREAST CANCER WHOSE DISEASE PROGRESSED AFTER PRIOR ENDOCRINE BASED TREATMENT FOR ADVANCED DISEASE (VERITAC-2)
Secondary IDs:	2022-500544-38-00 [EU CTIS]

Study Status


Record Verification:	December 2022
Overall Status:	Not yet recruiting
Study Start:	December 15, 2022
Primary Completion:	August 15, 2024 [Anticipated]
Study Completion:	May 15, 2028 [Anticipated]

First Submitted:	November 16, 2022
First Submitted that Met QC Criteria:	December 8, 2022
First Posted:	December 16, 2022 [Actual]

Last Update Submitted that Met QC Criteria:	December 8, 2022
Last Update Posted:	December 16, 2022 [Actual]

Sponsor/Collaborators


Sponsor:	Pfizer
Responsible Party:	Sponsor
Collaborators:	Arvinas Estrogen Receptor, Inc.

Oversight


U.S. FDA-regulated Drug:	Yes
U.S. FDA-regulated Device:	No
Data Monitoring:	Yes

Study Description

Brief Summary:

A study to learn about a new medicine called ARV-471 (PF-07850327) in people who have advanced metastatic breast cancer.

Detailed Description:

The purpose of this study is to learn about the safety and effects of the study medicine ARV-471 (PF-07850327) compared to fulvestrant (FUL) in participants with advanced breast cancer. FUL is a medicine already used for treatment of breast cancer while ARV-471 is a new medicine.

This study is seeking participants with breast cancer who:

Have a disease that comes back in the place where it started or in the nearby region (locoregional recurrent disease) or have a disease that has spread to other parts of the body (metastatic) and cannot be fully cured by surgery or radiation therapy
Are responsive to hormonal therapy such as tamoxifen (it is called estrogen receptor positive disease)
Have received one line of CDK4/6 inhibitor therapy (for example palbociclib) in combination with endocrine therapy (for example letrozole) for advanced disease.
Allowed up to one additional endocrine therapy (for example exemestane) for advanced disease.

Half of the participants will be given ARV-471 while half of the participants will be given FUL.

Participants will take ARV-471 by mouth with food, one time a day. During the first treatment cycle participants will be given FUL by shots into the muscles on Day 1 and again 2 weeks later. Afterwards, FUL shots will be given on the first day of each new treatment cycle. One treatment cycle is 28 days

Participants will receive the study medicine until their breast cancer worsens or side effects become too severe. Participants will have visits at the study clinic about every 4 weeks.

Conditions


Conditions:	Advanced Breast Cancer
Keywords:	ER(+)/HER2(-) Advanced Breast Cancer Advanced cancer of the breast Breast neoplasm Breast tumor Breast cancer Fulvestrant ARV-471 Estrogen receptor positive Metastatic breast cancer ER degrader PROTAC

Study Design


Study Type:	Interventional
Primary Purpose:	Treatment
Study Phase:	Phase 3
Interventional Study Model:	Parallel Assignment
Number of Arms:	2
Masking:	None (Open Label)
Allocation:	Randomized
Enrollment:	561 [Anticipated]

Arms and Interventions

Arms	Assigned Interventions
Experimental: ARV-471	Drug: ARV-471 orally, once daily on a 28-day continuous dosing schedule Other Names: PF-07850327
Active Comparator: Fulvestrant	Drug: Fulvestrant intramuscularly on Days 1 and 15 of Cycle 1 and then on Day 1 of each cycle starting from C2D1 (28-day cycle)

Outcome Measures


Primary Outcome Measures:
1.	Progression Free Survival (PFS) [ Time Frame: From randomization date (every 8 weeks for the first 48 weeks and then every 12 weeks thereafter) to date of first documentation of progression OR death (approximately 2 years). ] Progression-free survival is defined as the time interval from the date of randomization to the date of first documented tumor progression determined by blinded independent central review (BICR) assessment as per Response Evaluation Criteria in Solid Tumors (RECIST 1.1) or death due to any cause, whichever come first.
Secondary Outcome Measures:
1.	Overall survival (OS) [ Time Frame: From randomization date (every 3 months) to date of death (approximately 3 years) ] Overall survival is defined as the time interval from the date of randomization to the date of documented death due to any cause.
2.	Objective Response Rate (ORR) [ Time Frame: From randomization date (every 8 weeks during the first 48 weeks and then every 12 weeks) to the date of progression OR death (approximately to 2 years). ] Objective response rate is defined as the proportion of participants who have a confirmed CR or PR, as best overall response assessed by BICR as per RECIST 1.1, from the date of randomization to the date of disease progression, death due to any cause, whichever occurs first.
3.	Duration of response (DR) [ Time Frame: From the date of the first objective response (every 8 weeks during the first 48 weeks and then every 12 week) to the date of disease progression or death (approximately to 2 years). ] Duration of response is defined as the time from first documented evidence of CR or PR until progressive disease (PD) as determined by BICR assessment as per RECIST 1.1 or death due to any cause, whichever occurs first.
4.	Clinical Benefit Rate [ Time Frame: From randomization date (every 8 weeks during the first 48 weeks and then every 12 weeks) to the date of progression or death (approximately to 2 years). ] Clinical benefit rate is defined as the proportion of participants who have a confirmed CR, PR at any time, or SD or nonCR/non PD for at least 24 weeks determined by BICR assessment as per RECIST 1.1, from the date of randomization until disease progression, death due to any cause, whichever occurs first.
5.	Number of participants with treatment emergent adverse events (TEAEs), serious adverse events (SAEs), electrocardiogram (ECG) and laboratory abnormalities [ Time Frame: From screening until 28 days after the last dose (approximately 2 years). ] Incidence of participants with TEAEs, SAEs ECGs and laboratory abnormalities. TEAE/SAE and laboratory abnormalities will be graded according to NCI CTCAE V5.
6.	QT Interval (QTc) [ Time Frame: From baseline to end of treatment (approximately 2 years). ] Triplicate 12-lead electrocardiogram (ECG) measurements (each recording separated by approximately 2 minutes) are performed.
7.	Plasma Concentration Versus Time of ARV-471 [ Time Frame: From randomization date up to cycle 7 (each cycle is 28 days). ] Plasma concentrations of ARV-471
8.	Health state utility and health status will be assessed using the European Quality of Life Group questionnaire with 5 dimensions and 5 levels per dimension (EQ-5D-5L) [ Time Frame: From screening and every cycle until cycle 6 (each cycle is 28 days), and then every other cycle until 28 days after the last dose (approximately 2 years). ] Change from baseline and time to deterioration between treatment comparison in Quality of Life using the EQ-5D 5L questionnaire.
9.	Disease-related Quality of Life will be assessed using the European Organization for Research and Treatment of Cancer (EORTC) core quality of life questionnaire (QLQ-C30) [ Time Frame: From screening and every cycle until cycle 6 (each cycle is 28 days), and then every other cycle until 28 days after the last dose (approximately 2 years). ] Change from baseline and time to deterioration between treatment comparison in Quality of Life using the EORTC QLQ-C30 questionnaire.
10.	Disease- and treatment-related Quality of Life will be assessed using the European Organization for Research and Treatment of Cancer (EORTC) breast cancer module (QLQ-BR23) questionnaire [ Time Frame: From screening and every cycle until cycle 6 (each cycle is 28 days), and then every other cycle until 28 days after the last dose (approximately 2 years). ] Change from baseline and time to deterioration between treatment comparison in Quality of Life Using the EORTC QLQ-BR23 (Breast) questionnaire.
11.	Clinical Pain and its impact on functioning will be assessed using Brief Pain Inventory Short Form (BPI-SF) questionnaire. [ Time Frame: From screening and every cycle until cycle 6 (cycle=28 days) and then every other cycle until 28 days after the last dose (appr. 2 yrs).The modified BPI-SF (worst pain severity and pain interference) daily from baseline until the EOT (appr 2 yrs) ] Change from baseline and time to deterioration between treatment comparison in Brief Pain Inventory Short Form questionnaire.
12.	circulating deoxyribonucleic acid (DNA) [ Time Frame: From baseline to end of treatment (approximately 2 years). ] Quantitative changes from baseline

Eligibility


Minimum Age:	18 Years
Maximum Age:
Sex:	All
Gender Based:
Accepts Healthy Volunteers:	No
Criteria:	Inclusion Criteria: Adult participants with loco-regional recurrent or metastatic breast disease not amenable to surgical resection or radiation therapy Confirmed diagnosis of ER+/HER2- breast cancer Prior therapies for locoregional recurrent or metastatic disease must fulfill all the following criteria: One line of CDK4/6 inhibitor therapy in combination with endocrine therapy ≤ 1 endocrine therapy in addition to CDK4/6 inhibitor with ET Most recent endocrine treatment duration must have been given for ≥6 months prior to disease progression Radiological progression during or after the last line of therapy Measurable disease evaluable per Response Evaluation Criterion in Solid Tumors (RECIST) v.1.1 or non-measurable bone-only disease Eastern Cooperative Oncology Group (ECOG) performance status 0-1 Participants should be willing to provide blood and tumor tissue Exclusion Criteria: Participants with advanced, symptomatic visceral spread, that are at risk of life-threatening complications in the short term Prior treatment with: ARV-471, fulvestrant, mTOR, PI3K, AKT pathway inhibitors, PARP inhibitor for any setting other investigational novel endocrine therapy (ie, SERD, SERCA, CERAN) for any setting prior CDK4/6 inhibitor treatment in the neoadjuvant/ adjuvant setting prior chemotherapy for advanced/metastatic disease Inadequate liver, kidney and bone marrow function Active brain metastases Participants with significant concomitant illness

Contacts/Locations


Central Contact Person:	Pfizer CT.gov Call Center Telephone: 1-800-718-1021 Email: ClinicalTrials.gov_Inquiries@pfizer.com
Study Officials:	Pfizer CT.gov Call Center Study Director Pfizer
Locations:

IPDSharing


Plan to Share IPD:	Yes Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.
	Supporting Information:
	Time Frame:
	Access Criteria:
	URL: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests

References


Citations:
Links:	URL: https://pmiform.com/clinical-trial-info-request?StudyID=C4891001 Description: To obtain contact information for a study center near you, click here.
Available IPD/Information: