A Study to Learn About Vepdegestrant When Given With PF-07220060 to People With Advanced or Metastatic Breast Cancer.

AN INTERVENTIONAL SAFETY AND EFFICACY PHASE 1B/2, OPEN-LABEL STUDY TO INVESTIGATE TOLERABILITY, PK, AND ANTITUMOR ACTIVITY OF VEPDEGESTRANT (ARV-471/PF-07850327), AN ORAL PROTEOLYSIS TARGETING CHIMERA, IN COMBINATION WITH PF-07220060 IN PARTICIPANTS AGED 18 YEARS AND OLDER WITH ER+/HER2- ADVANCED OR METASTATIC BREAST CANCER

The purpose of this study is to learn about the safety and effects of giving vepdegestrant along with PF-07220060. Vepdegestrant is studied to see if it can be a possible treatment for advanced metastatic breast cancer. This type of cancer would have spread from where it started (breast) to other parts of the body and would be tough to treat. The study is seeking for participants who have breast cancer that:

• is hard to treat (advanced) and may have spread to other organs (metastatic).
• is sensitive to hormonal therapy (it is called estrogen receptor positive).
• is no longer responding to treatments taken before starting this study.

All the participants will receive vepdegestrant and PF-07220060. Both medicines will be taken by mouth. The medicines will be taken at home. The experience of people receiving the study medicines will be studied. This will help see if the study medicines are safe and effective. Participants will continue to take vepdegestrant and PF-07220060 until:

• their cancer is no longer responding, or
• side effects become too severe. They will have visits at the study clinic about every 4 weeks.

Study Overview

• Status: Active, not recruiting
• Conditions: Breast Cancer
• Intervention / Treatment: Drug: vepdegestrant; Drug: PF-07220060

Detailed Description

C4891026 is a prospective, open-label, multicenter, Phase 1b/2 study to evaluate the safety, antitumor activity, and pharmacokinetic (PK) of vepdegestrant in combination with PF-07220060 in the treatment of participants with Estrogen Receptor Positive/Human Epidermal Growth Factor Receptor 2 Negative (ER+/HER2-) Advanced or Metastatic Breast Cancer.

• Study Type: Interventional
• Enrollment (Actual): 71
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Belgium
  • Antwerpen
    • Edegem, Antwerpen, Belgium, 2650
      • Antwerp University Hospital
  • Bruxelles-capitale, Région de
    • Anderlecht, Bruxelles-capitale, Région de, Belgium, 1070
      • Institut Jules Bordet
  • Vlaams-brabant
    • Leuven, Vlaams-brabant, Belgium, 3000
      • UZ Leuven
  • West-vlaanderen
    • Kortrijk, West-vlaanderen, Belgium, 8500
      • AZ Groeninge Campus Kennedylaan
• Canada
  • Ontario
    • Ottawa, Ontario, Canada, K1H 8L6
      • The Ottawa Hospital - General Campus
    • Toronto, Ontario, Canada, M5G 2M9
      • Princess Margaret Cancer Centre
    • Toronto, Ontario, Canada, M4N 3M5
      • Sunnybrook Research Institute
• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510060
      • Sun Yat-sen University Cancer Center
  • Hubei
    • Wuhan, Hubei, China, 430023
      • Wuhan Union Hospital Cancer Center
  • Shaanxi
    • Xi'an, Shaanxi, China, 710061
      • The First Affiliated Hospital of Xi'an Jiaotong University
• France
  • Hérault
    • Montpellier, Hérault, France, 34298
      • Institut Régional du Cancer Montpellier
  • Loire-atlantique
    • Saint-Herblain, Loire-atlantique, France, 44805
      • Institut de Cancérologie de l'Ouest
  • Provence-Alpes-Côte d'Azur Region
    • Marseille, Provence-Alpes-Côte d'Azur Region, France, 13273
      • Institut Paoli-Calmettes
• Japan
  • Tokyo, Japan, 142-8666
    • Showa Medical University Hospital
  • Chiba
    • Kashiwa, Chiba, Japan, 277-8577
      • National Cancer Center Hospital East
  • Kanagawa
    • Yokohama, Kanagawa, Japan, 2418515
      • Kanagawa cancer center
  • Tokyo
    • Chuo-ku, Tokyo, Japan, 104-0045
      • National Cancer Center Hospital
• Puerto Rico
  • Mayagüez, Puerto Rico, 00680
    • BRCR Global - Mayaguez Administrative Office
  • Mayagüez, Puerto Rico, 00682
    • BRCR Global - Mayagüez
  • Rio Piedras, Puerto Rico, 00935
    • Pan American Center for Oncology Trials, LLC
• Spain
  • Seville, Spain, 41013
    • Hospital Universitario Virgen Del Rocio
  • Barcelona [barcelona]
    • Barcelona, Barcelona [barcelona], Spain, 08035
      • Hospital Universitari Vall d'Hebron
  • Lleida [lérida]
    • Lleida, Lleida [lérida], Spain, 25198
      • Hospital Universitario Arnau de Vilanova de Lleida
  • Madrid, Comunidad de
    • Madrid, Madrid, Comunidad de, Spain, 28041
      • Hospital Universitario 12 de Octubre
• United States
  • Arkansas
    • Fayetteville, Arkansas, United States, 72703
      • Highlands Oncology
    • Rogers, Arkansas, United States, 72758
      • Highlands Oncology
    • Springdale, Arkansas, United States, 72762
      • Highlands Oncology Group
  • California
    • Irvine, California, United States, 92618
      • Hoag Hospital Irvine
    • Irvine, California, United States, 92618
      • Hoag Health Center Irvine
    • Newport Beach, California, United States, 92663
      • Hoag Memorial Hospital Presbyterian
    • Palo Alto, California, United States, 94304
      • Stanford Cancer Center
    • Palo Alto, California, United States, 94304
      • Clinical and Translational Research Unit (CTRU)
    • Palo Alto, California, United States, 94304
      • Stanford Cancer Institute - Clinical Trials Office
    • San Francisco, California, United States, 94158
      • UCSF Medical Center at Mission Bay
  • Colorado
    • Fort Collins, Colorado, United States, 80524
      • UCHealth Poudre Valley Hospital
    • Fort Collins, Colorado, United States, 80528
      • UCHealth Harmony
    • Greeley, Colorado, United States, 80634
      • UCHealth Greeley Hospital
    • Loveland, Colorado, United States, 80538
      • UCHealth - Medical Center of the Rockies
  • Connecticut
    • New Haven, Connecticut, United States, 06511
      • Smilow Cancer Hospital Phase 1 Unit
    • New Haven, Connecticut, United States, 06510
      • Smilow Cancer Hospital - Yale New Haven Health
    • New Haven, Connecticut, United States, 06510
      • Yale - New Haven Hospital - Yale Cancer Center
    • Trumbull, Connecticut, United States, 06611
      • Smilow Cancer Hospital - Trumbull
  • Michigan
    • Grand Rapids, Michigan, United States, 49546
      • START Midwest
  • New Jersey
    • Basking Ridge, New Jersey, United States, 07920
      • MSK Basking Ridge
    • Middletown, New Jersey, United States, 07748
      • MSK Monmouth
    • Montvale, New Jersey, United States, 07645
      • MSK Bergen
  • New York
    • Commack, New York, United States, 11725
      • MSK Commack
    • Harrison, New York, United States, 10604
      • MSK Westchester
    • New York, New York, United States, 10065
      • Memorial Sloan Kettering Cancer Center
    • New York, New York, United States, 10022
      • Rockefeller Outpatient Pavilion (53rd Street)
    • New York, New York, United States, 10065
      • Evelyn H. Lauder Breast and Imaging Center (BAIC).
    • Uniondale, New York, United States, 11553
      • MSK Nassau
  • Texas
    • San Antonio, Texas, United States, 78229
      • START San Antonio
  • Utah
    • Farmington, Utah, United States, 84025
      • University of Utah, Farmington Health Center
    • Salt Lake City, Utah, United States, 84112
      • Huntsman Cancer Institute
    • Salt Lake City, Utah, United States, 84106
      • University of Utah, Sugar House Health Center
    • South Jordan, Utah, United States, 84106
      • South Jordan Health Center - University of Utah
    • West Valley City, Utah, United States, 84119
      • START Mountain Region

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Histological or cytological diagnosis of breast cancer. At time of enrollment this must not be amenable to surgical resection with curative intent (≥1% ER+ stained cells as per local practice on the most recent tumor biopsy HER2- tumor by IHC or in-situ hybridization per ASCO/CAP).

• prior anticancer therapies: Phase 1b: at least 1 line of SOC for A/MBC; Prior fulvestrant allowed; ≤1 prior chemotherapy line (no antibody-drug conjugates permitted) for A/MBC setting allowed. Phase 2: At least one and maximum 2 lines of ET in A/MBC setting and most recent ET-based regimen for >6 months.

  1, and only 1, prior CDK4/6 inhibitor-based regimen required. Up to 1 prior regimen of cytotoxic chemotherapy (no antibody-drug conjugates permitted) in the A/MBC setting; Prior fulvestrant allowed.

• Participant with only non-measurable lesion (Phase1b) or at least 1 measurable lesion as defined by RECIST v1.1. (Phase2) are eligible.

• ECOG PS = 0 or 1 (Phase1b) ; ≤2 (Phase2)

Exclusion Criteria:

• visceral crisis at risk of life-threatening complications in the short term.
• Any condition precluding an adeguate absorption of study interventions.
• newly diagnosed brain metastases, or symptomatic central nervous system (CNS) metastases, carcinomatous meningitis, or leptomeningeal disease. Participants with a history of CNS metastases or cord compression are eligible if they have been definitively treated, clinically stable and discontinued anti-seizure medications and corticosteroids for at least 28 days prior to enrollment in the of study.
• history of any other tumor malignancies within the past 3 years, except for the following: (1) adequately treated basal or squamous cell carcinoma of the skin; (2) curatively treated in situ carcinoma of the cervix. Inflammatory breast cancer are excluded
• impaired cardiovascular function or clinically significant cardiovascular diseases.
• concurrent administration of medications, food, or herb supplements that are strong inhibitors/inducers of CYP3A or UGT2B7, moderate inducers of CYP34 (Phase1b only) and drugs known to predispose to Torsade de Pointes or QT interval prolongation.
• renal impairment, not adequate liver function and/or bone marrow function.
• known active infection

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: vepdegestrant in combination with PF-07220060; vepdegestrant administered orally once daily (QD) continuously and PF-07220060 administered orally twice daily (BID) continuously on 28-day cycles

Drug: vepdegestrant; Daily oral dosages of vepdegestrant continuously, dose escalation/de-escalation in Phase 1b until recommended phase 2 dose (RP2D) determined, cycles lasting 28 days; Other Names: ARV-471 / PF07850327; Drug: PF-07220060; Daily oral dosages of PF-07220060 continuously, dose escalation/de-escalation in Phase 1b until recommended phase 2 dose (RP2D) determined, cycles lasting 28 days

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Dose-Limiting Toxicities (DLTs): Phase 1b	Hematological DLT: neutropenic fever; Grade>=3 thrombocytopenia associated with Grade>=2(clinically significant)bleeding and Grade4 neutropenia/thrombocytopenia lasting <7 days. Non-hematological: Grade>=3 toxicities clinically significant,except those that were not been maximally treated;Grade 2 aspartate aminotransferase(AST), alanine aminotransferase(ALT)/alkaline phosphatase(ALP) levels at baseline as result of liver/bone metastasis,AST,ALT and ALP level>8*baseline/AST/ALT >5*baseline for>=14 days; Hy's Law(concomitant ALT/AST elevation of >=3*upper limit of normal [ULN], total bilirubin elevation>=2*ULN without clear alternative etiology); Grade≥3 electrolyte abnormality with clinical sequelae; QTcF prolongation:any Grade>=3 QT prolongation without clear alternative etiology;any adverse event (AE) attributed to Vepdegestrant and/or PF-07220060 resulting in failure to deliver 75% of doses for either/both agents and any death not clearly due to underlying disease/extraneous causes.	Cycle 1 (28 days)
Percentage of Participants With Confirmed Objective Response (OR) by Derived Investigator Assessment: Phase 2	OR was defined as best overall response (BOR) of confirmed complete response (CR) or partial response (PR) according to response evaluation criteria in solid tumors (RECIST) version (v) 1.1. CR was defined as complete disappearance of all target lesions, except for nodal disease, complete disappearance of all non-target lesions and no new lesions. All nodes, both target and non-target, must decrease to normal (short axis <10 millimeter [mm]). PR was defined as at least a >=30% decrease from baseline in the sum of diameters of all target lesions. The short diameter was used in the sum for nodal target lesions, while the longest diameter was used in the sum for non-nodal target lesions, all target lesions were assessed.	From the date of first dose of study treatment combination until the first documentation of disease progression (PD), death or start of new anticancer therapy, whichever occurred first (maximum treatment exposure of 9.5 months for Phase 2)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Treatment Emergent Adverse Events (TEAEs), Treatment Emergent Serious Adverse Events (TESAEs) and Treatment Related TEAEs: Phase 1b	AE: any untoward medical occurrence in clinical study participant, temporally associated with use of study treatment, whether or not considered related to study treatment. Serious adverse event (SAE): any untoward medical occurrence, at any dose met one or more of following criteria: death, life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability/incapacity, congenital anomaly/birth defect or other important medical events. AEs includes both SAEs and all other AEs (non-SAEs). TEAEs will be those events with onset dates occurring during the on-treatment period. Relatedness to study drug judged by investigator.	From the date of first dose of study treatment combination through study completion
Number of Participants With Laboratory Abnormalities: Phase 1b	Laboratory parameters assessed: hemoglobin, platelets, white blood cells (WBC), absolute neutrophils, absolute lymphocytes, absolute monocytes, absolute eosinophils, absolute basophils, alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), sodium, potassium, magnesium, chloride, total calcium, total bilirubin, urea or blood urea nitrogen (BUN), creatinine, estimated glomerular filtration rate (eGFR), uric acid, glucose (fasted), albumin, phosphorus, lipase and amylase.	From the date of first dose of study treatment combination through study completion
Number of Participants With Electrocardiogram (ECG) Abnormalities: Phase 1b	Twelve lead ECGs were measured with the participant in a supine position after at least 5 minutes.	From the date of first dose of study treatment combination through study completion
Percentage of Participants With Confirmed OR by Derived Investigator Assessment: Phase 1b	OR was defined as BOR of confirmed CR or PR according to RECIST v 1.1. CR was defined as complete disappearance of all target lesions, except for nodal disease, complete disappearance of all non-target lesions and no new lesions. All nodes, both target and non-target, must decrease to normal (short axis <10 mm). PR was defined as at least a >=30% decrease from baseline in the sum of diameters of all target lesions. The short diameter was used in the sum for nodal target lesions, while the longest diameter was used in the sum for non-nodal target lesions, all target lesions were assessed.	From the date of first dose of study treatment combination through study completion
Duration of Response (DOR) by Derived Investigator Assessment: Phase 1b	DoR: for participants with OR: time from first documentation of CR/PR to first documentation of PD/death. CR: complete disappearance of all target lesions (L), except nodal disease, complete disappearance of all non-target L and no new L. Both target and non-target nodes, must decrease to normal. PR: >=30% decrease from baseline in sum of diameters of target L. Short diameter used in sum for nodal target L, longest diameter used in sum for non-nodal target L. PD: 20% increase in sum of diameter of target measurable L above smallest sum observed, minimum absolute increase of 5 mm for target L/unequivocal progression of pre-existing L for non-target L. DOR censored on date of last adequate disease assessment for participants who did not have DOR event, discontinued study treatment due to withdrawal of consent prior to event, started new anticancer therapy prior to event, had event after gap of >2 missing disease assessments, or lost to follow-up. Kaplan-Meier method will be used.	From the date of first dose of study treatment combination through study completion
Clinical Benefit Response (CBR) by Derived Investigator Assessment: Phase 1b	CBR was defined as percentage of participants with BOR of confirmed CR or PR at any time, or stable disease (SD) >=24 weeks as per RECIST v1.1. CR: complete disappearance of all target lesions, except for nodal disease, complete disappearance of all non-target lesions and no new lesions. All nodes, both target and non-target, must decrease to normal (short axis<10 mm). PR: at least >=30% decrease from baseline in sum of diameters of all target lesions. Short diameter was used in sum for nodal target lesions, while longest diameter was used in sum for non-nodal target lesions, all target lesions were assessed. SD: did not qualify for CR, PR, PD. All target lesions were assessed. PD: 20% increase in sum of diameters of target measurable lesions above smallest sum observed, minimum absolute increase of 5mm for target lesions/unequivocal progression of pre-existing lesions for non-target lesion.	From the date of first dose of study treatment combination through study completion
Progression Free Survival (PFS) by Derived Investigator Assessment: Phase 1b	PFS was defined as the time from the date of first dose of study interventions to the date of first documentation of PD or death due to any cause, whichever occurred first as per RECIST v1.1. PD: 20% increase in sum of diameters of target measurable lesions above smallest sum observed, minimum absolute increase of 5mm for target lesions/unequivocal progression of pre-existing lesions for non-target lesion. PFS was censored on the date of last adequate disease assessment for those who did not have a PFS event, discontinued the study treatment due to withdrawal of consent prior to an event, started a new anticancer therapy prior to an event, had an event after a gap of 2 or more missing disease assessments, or lost to follow-up. Kaplan-Meier method will be used.	From the date of first dose of study treatment combination through study completion
Plasma Concentration of Vepdegestrant (ARV-471) and Its Epimer ARV-473: Phase 1b	Plasma concentrations of ARV-471 and its epimer ARV-473 were reported in this outcome measure.	Cycle 1, Day 8: Pre-dose; Cycle 1 Day 15: Pre-dose, 30 minutes, 1, 2, 4 ,6, 8 and 12 hours post-dose; Cycle 2 Days 1 and 15: Pre-dose, anytime between 4 to 8 hour post-dose; Cycles 3, 5, and 7, Day 1: Pre-dose
Plasma Concentration of PF-07220060: Phase 1b		Pre-dose (0 hour) of Day 8 of Cycle 1; pre-dose (0 hour), 0.5,1,2,4,6,8 and 12 hours post-dose of Day 15 of Cycle 1; Pre-dose (0 hour) and anytime between 4 to 8 hour post-dose of Day 1 and 15 of Cycle 2; Pre-dose (0 hour) of Day 1 of Cycle 3, 5 and 7
Steady State Maximum Observed Plasma Concentration (Cmax,ss) of Vepdegestrant (ARV-471) and Its Epimer ARV-473: Phase 1b	Cmax,ss was the steady-state maximum concentration of ARV-471 after multiple doses and was directly observed from data. ARV-473 is an epimer of ARV-471.	Predose (0 hours), 0.5, 1, 2, 4, 6, 8, and 12 hours post dose on Cycle 1 Day 15
Cmax,ss of PF-07220060: Phase 1b		Predose (0 hours), 0.5, 1, 2, 4, 6, 8, and 12 hours post dose on Cycle 1 Day 15
Steady State Time to Maximum Plasma Concentration (Tmax,ss) of Vepdegestrant (ARV-471) and Its Epimer ARV-473: Phase 1b	Tmax,ss was the steady-state time to maximum plasma concentration after multiple doses and was directly observed from data. ARV-473 is an epimer of ARV-471. ARV-473 is an epimer of ARV-471.	Predose (0 hours), 0.5, 1, 2, 4, 6, 8, and 12 hours post dose on Cycle 1 Day 15
Tmax,ss of PF-07220060: Phase 1b	Tmax,ss was the steady-state time to maximum plasma concentration after multiple doses and was directly observed from data.	Predose (0 hours), 0.5, 1, 2, 4, 6, 8, and 12 hours post dose on Cycle 1 Day 15
Steady State Area Under the Plasma Concentration-Time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUClast,ss) of Vepdegestrant (ARV-471) and Its Epimer ARV-473: Phase 1b	AUClast,ss was defined as area under the plasma concentration time curve from time zero to the last measurable concentration as steady state. AUClast,ss was calculated using linear/log trapezoidal method.	Predose (0 hours), 0.5, 1, 2, 4, 6, 8, and 12 hours post dose on Cycle 1 Day 15
AUClast,ss of PF-07220060: Phase 1b	AUClast,ss was defined as area under the plasma concentration time curve from time zero to the last measurable concentration as steady state. AUClast,ss was calculated using linear/log trapezoidal method.	Predose (0 hours), 0.5, 1, 2, 4, 6, 8, and 12 hours post dose on Cycle 1 Day 15
Apparent Total Clearance (CL/F) of Vepdegestrant (ARV-471): Phase 1b	Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. CL/F was calculated as dose administered divided by AUCinf. AUCinf was calculated as AUClast + (Clast/kel), where, AUClast= area under the concentration-time curve from time 0 to time of last measurable concentration, Clast was the predicted plasma concentration at the last quantifiable time point estimated from the log-linear regression analysis and kel was the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve.	Predose (0 hours), 0.5, 1, 2, 4, 6, 8, and 12 hours post dose on Cycle 1 Day 15
CL/F of PF-07220060: Phase 1b	Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. CL/F was calculated as dose administered divided by AUCinf. AUCinf was calculated as AUClast + (Clast/kel), where, AUClast= area under the concentration-time curve from time 0 to time of last measurable concentration, Clast was the predicted plasma concentration at the last quantifiable time point estimated from the log-linear regression analysis and kel was the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve.	Predose (0 hours), 0.5, 1, 2, 4, 6, 8, and 12 hours post dose on Cycle 1 Day 15
Apparent Volume of Distribution (Vz/F) of PF-07220060: Phase 1b	Vz/F was calculated as Dose/(AUCinf * kel). AUCinf was calculated as AUClast + (Clast/kel), where, AUClast= area under the concentration-time curve from time 0 to time of last measurable concentration, Clast was the predicted plasma concentration at the last quantifiable time point estimated from the log-linear regression analysis and kel was the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve.	Predose (0 hours), 0.5, 1, 2, 4, 6, 8, and 12 hours post dose on Cycle 1 Day 15
Terminal Half-Life (t1/2) of PF-07220060: Phase 1b	T1/2 was calculated as loge(2)/kel, where kel is the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve.	Predose (0 hours), 0.5, 1, 2, 4, 6, 8, and 12 hours post dose on Cycle 1 Day 15
DOR by Derived Investigator Assessment: Phase 2	DOR: for participants with OR: time from first documentation of CR/PR to first documentation of PD/death. CR: complete disappearance of all target lesions (L), except nodal disease, complete disappearance of all non-target L and no new L. Both target and non-target nodes, must decrease to normal. PR: >=30% decrease from baseline in sum of diameters of target L. Short diameter used in sum for nodal target L, longest diameter used in sum for non-nodal target L. PD: 20% increase in sum of diameter of target measurable L above smallest sum observed, minimum absolute increase of 5 mm for target L/unequivocal progression of pre-existing L for non-target L. DOR censored on date of last adequate disease assessment for participants who did not have DOR event, discontinued study treatment due to withdrawal of consent prior to event, started new anticancer therapy prior to event, had event after gap of >2 missing disease assessments, or lost to follow-up. Kaplan-Meier method will be used.	From the date of first dose of study treatment combination through study completion
Percentage of Participants With CBR by Derived Investigator Assessment: Phase 2	CBR was defined as percentage of participants with BOR of confirmed CR or PR at any time, or stable disease (SD) >=24 weeks as per RECIST v1.1. CR: complete disappearance of all target lesions, except for nodal disease, complete disappearance of all non-target lesions and no new lesions. All nodes, both target and non-target, must decrease to normal (short axis<10 mm). PR: at least >=30% decrease from baseline in sum of diameters of all target lesions. Short diameter was used in sum for nodal target lesions, while longest diameter was used in sum for non-nodal target lesions, all target lesions were assessed. SD: did not qualify for CR, PR, PD. All target lesions were assessed. PD: 20% increase in sum of diameters of target measurable lesions above smallest sum observed, minimum absolute increase of 5mm for target lesions/unequivocal progression of pre-existing lesions for non-target lesion.	From the date of first dose of study treatment combination through study completion
PFS by Derived Investigator Assessment: Phase 2	PFS was defined as the time from the date of first dose of study interventions to the date of first documentation of PD or death due to any cause, whichever occurred first as per RECIST v1.1. PD: 20% increase in sum of diameters of target measurable lesions above smallest sum observed, minimum absolute increase of 5mm for target lesions/unequivocal progression of pre-existing lesions for non-target lesion. PFS was censored on the date of last adequate disease assessment for those who did not have a PFS event, discontinued the study treatment due to withdrawal of consent prior to an event, started a new anticancer therapy prior to an event, had an event after a gap of 2 or more missing disease assessments, or lost to follow-up. Kaplan-Meier method will be used.	From the date of first dose of study treatment combination through study completion
Overall Survival (OS): Phase 2	OS was defined as the time from the date of first dose of study treatment combination to the date of death due to any cause. Participants last known to be alive were censored at the date of last contact. Kaplan-Meier method will be used.	From the date of first dose of study treatment combination through study completion
Number of Participants With TEAEs, TESAEs and Treatment Related TEAEs: Phase 2	AE: any untoward medical occurrence in clinical study participant, temporally associated with use of study treatment, whether or not considered related to study treatment. SAE: any untoward medical occurrence, at any dose met one or more of following criteria: death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability/incapacity, congenital anomaly/birth defect or other important medical events. AEs includes both SAEs and all other AEs (non-SAEs). TEAEs will be those events with onset dates occurring during the on-treatment period. Relatedness to study drug judged by investigator.	From the date of first dose of study treatment combination through study completion
Number of Participants With ECG Abnormalities: Phase 2	Twelve lead ECGs were measured with the participant in a supine position after at least 5 minutes.	From the date of first dose of study treatment combination through study completion
Number of Participants With Laboratory Abnormalities: Phase 2	Laboratory parameters assessed included hemoglobin, platelets, WBC, absolute neutrophils, absolute lymphocytes, absolute monocytes, absolute eosinophils, absolute basophils, ALT, AST, ALP, sodium, potassium, magnesium, chloride, total calcium, total bilirubin, urea or BUN, creatinine, eGFR, uric acid, glucose (fasted), albumin, phosphorus, lipase and amylase.	From the date of first dose of study treatment combination through study completion
Plasma Concentration of Vepdegestrant (ARV-471) and Its Epimer ARV-473: Phase 2	Plasma concentrations of ARV-471 and its epimer ARV-473 were reported in this outcome measure.	Cycle 1, Day 15 and Cycle 2 Days 1 and 15: Pre-dose, anytime between 4 to 8 hour post-dose; Cycles 3, 5, and 7, Day 1: Pre-dose
Plasma Concentration of PF-07220060: Phase 2	Plasma concentrations of ARV-471 and its epimer ARV-473 were reported in this outcome measure.	Cycle 1, Day 15 and Cycle 2 Days 1 and 15: Pre-dose, anytime between 4 to 8 hours post-dose; Cycles 3, 5, and 7, Day 1: Pre-dose
Change From Baseline in Circulating Tumor Deoxyribonucleic Acid (ctDNA) Plasma Level: Phase 2		Baseline and up to End of Treatment

Collaborators and Investigators

• Sponsor: Pfizer
• Collaborators: Arvinas Estrogen Receptor, Inc.
• Investigators: Study Director: Pfizer CT.gov Call Center, Pfizer

Publications and helpful links

Helpful Links

• <p>To obtain contact information for a study center near you, click here.</p>

Study record dates

Study Major Dates

• Study Start (Actual): February 19, 2024
• Primary Completion (Actual): September 5, 2025
• Study Completion (Estimated): May 25, 2027

Study Registration Dates

• First Submitted: December 13, 2023
• First Submitted That Met QC Criteria: January 4, 2024
• First Posted (Actual): January 16, 2024

Study Record Updates

• Last Update Posted (Actual): September 30, 2026
• Last Update Submitted That Met QC Criteria: September 3, 2026
• Last Verified: September 1, 2026

More Information

Terms related to this study

• Keywords: metastatic breast cancer; Proteolysis Targeting Chimera (PROTAC)
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Skin Diseases; Breast Diseases; Skin and Connective Tissue Diseases; Breast Neoplasms
• Other Study ID Numbers: C4891026; 2023-508130-33-00 (Registry Identifier: CTIS (EU)); TACTIVE-K (Other Identifier: Alias Study Number); 2023 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

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.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No