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

Sponsor

Pfizer (Industry)

Overall Status

Recruiting

CT.gov ID

NCT05654623

Collaborator

Arvinas Estrogen Receptor, Inc. (Industry)

560

Enrollment

Locations

Arms

63.8

Anticipated Duration (Months)

Patients Per Site

0.6

Patients Per Site Per Month

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
Advanced Breast Cancer	Drug: ARV-471 Drug: Fulvestrant	Phase 3

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

560 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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)

Anticipated Study Start Date :

Feb 17, 2023

Anticipated Primary Completion Date :

Nov 13, 2024

Anticipated Study Completion Date :

Jun 13, 2028

Arms and Interventions

Arm	Intervention/Treatment
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)

Arm

Intervention/Treatment

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

Progression Free Survival (PFS) [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

Overall survival (OS) [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.
Objective Response Rate (ORR) [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.
Duration of response (DR) [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.
Clinical Benefit Rate [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.
Number of participants with treatment emergent adverse events (TEAEs), serious adverse events (SAEs), electrocardiogram (ECG) and laboratory abnormalities [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.
QT Interval (QTc) [From baseline to end of treatment (approximately 2 years).]
Triplicate 12-lead electrocardiogram (ECG) measurements (each recording separated by approximately 2 minutes) are performed.
Plasma Concentration Versus Time of ARV-471 [From randomization date up to cycle 7 (each cycle is 28 days).]
Plasma concentrations of ARV-471
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) [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.
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) [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.
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 [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.
Clinical Pain and its impact on functioning will be assessed using Brief Pain Inventory Short Form (BPI-SF) questionnaire. [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.
circulating deoxyribonucleic acid (DNA) [From baseline to end of treatment (approximately 2 years).]
Quantitative changes from baseline

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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 and Locations

Locations

	Site	City	State	Country	Postal Code
1	3T Radiology LLC	Coconut Creek	Florida	United States	33073
2	Lakeland Regional Cancer Center	Lakeland	Florida	United States	33805
3	Broward P.E.T. Imaging Center	Lauderdale Lakes	Florida	United States	33313
4	Mid Florida Hematology and Oncology Center	Orange City	Florida	United States	32763
5	POM MRI & Radiology Centers	Plantation	Florida	United States	33313
6	BRCR Global	Plantation	Florida	United States	33322
7	Impression Imaging	Tamarac	Florida	United States	33321
8	Hematology-Oncology Associates of Central New York, PC	East Syracuse	New York	United States	13057
9	Hematology Oncology Associates of Rockland	Nyack	New York	United States	10960
10	Frank C Love Cancer Institute	Oklahoma City	Oklahoma	United States	73102
11	Hightower Clinical Trial Services	Oklahoma City	Oklahoma	United States	73102
12	SSM Health Medical Group - St Anthony	Oklahoma City	Oklahoma	United States	73102
13	Pan American Center for Oncology Trials	Rio Piedras		Puerto Rico	00935
14	FDI Clinical Research	San Juan		Puerto Rico	00927