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

Browse trials for

• Breast Neoplasms 12,543

Keywords

• Proteolysis Targeting Chimera (PROTAC)
• metastatic breast cancer

Breast Neoplasms

12,543 studies on the registry are indexed under Breast Neoplasms; 2,892 are open to participants now.

This study's enrollment of 71 is close to the median of 72 across 9,302 interventional studies indexed under Breast Neoplasms.

Lead sponsor

Pfizer is the lead sponsor of 3,244 studies on the registry; 139 are open to participants now.

Of its 582 completed or terminated interventional studies of FDA-regulated products, 381 (65%) have results posted.

Study arms

• 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 · Drug: PF-07220060

Interventions

• Drugvepdegestrant

  Daily oral dosages of vepdegestrant continuously, dose escalation/de-escalation in Phase 1b until recommended phase 2 dose (RP2D) determined, cycles lasting 28 days

  Also known as: ARV-471 / PF07850327

• DrugPF-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

Primary outcomes

1. 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.

   Time frame: Cycle 1 (28 days)

2. 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.

   Time frame: 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 outcomes

1. 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.

   Time frame: From the date of first dose of study treatment combination through study completion

2. 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.

   Time frame: From the date of first dose of study treatment combination through study completion

3. 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.

   Time frame: From the date of first dose of study treatment combination through study completion

4. 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.

   Time frame: From the date of first dose of study treatment combination through study completion

5. 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.

   Time frame: From the date of first dose of study treatment combination through study completion

6. 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.

   Time frame: From the date of first dose of study treatment combination through study completion

7. 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.

   Time frame: From the date of first dose of study treatment combination through study completion

8. 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.

   Time frame: 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

9. Plasma Concentration of PF-07220060: Phase 1b

   Time frame: 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

10. 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.

    Time frame: Predose (0 hours), 0.5, 1, 2, 4, 6, 8, and 12 hours post dose on Cycle 1 Day 15

11. Cmax,ss of PF-07220060: Phase 1b

    Time frame: Predose (0 hours), 0.5, 1, 2, 4, 6, 8, and 12 hours post dose on Cycle 1 Day 15

12. 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.

    Time frame: Predose (0 hours), 0.5, 1, 2, 4, 6, 8, and 12 hours post dose on Cycle 1 Day 15

13. 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.

    Time frame: Predose (0 hours), 0.5, 1, 2, 4, 6, 8, and 12 hours post dose on Cycle 1 Day 15

14. 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.

    Time frame: Predose (0 hours), 0.5, 1, 2, 4, 6, 8, and 12 hours post dose on Cycle 1 Day 15

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.

    Time frame: Predose (0 hours), 0.5, 1, 2, 4, 6, 8, and 12 hours post dose on Cycle 1 Day 15

16. 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.

    Time frame: Predose (0 hours), 0.5, 1, 2, 4, 6, 8, and 12 hours post dose on Cycle 1 Day 15

17. 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.

    Time frame: Predose (0 hours), 0.5, 1, 2, 4, 6, 8, and 12 hours post dose on Cycle 1 Day 15

18. 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.

    Time frame: Predose (0 hours), 0.5, 1, 2, 4, 6, 8, and 12 hours post dose on Cycle 1 Day 15

19. 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.

    Time frame: Predose (0 hours), 0.5, 1, 2, 4, 6, 8, and 12 hours post dose on Cycle 1 Day 15

20. 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.

    Time frame: From the date of first dose of study treatment combination through study completion

21. 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.

    Time frame: From the date of first dose of study treatment combination through study completion

22. 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.

    Time frame: From the date of first dose of study treatment combination through study completion

23. 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.

    Time frame: From the date of first dose of study treatment combination through study completion

24. 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.

    Time frame: From the date of first dose of study treatment combination through study completion

25. 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.

    Time frame: From the date of first dose of study treatment combination through study completion

26. 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.

    Time frame: From the date of first dose of study treatment combination through study completion

27. 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.

    Time frame: 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

28. Plasma Concentration of PF-07220060: Phase 2

    Plasma concentrations of ARV-471 and its epimer ARV-473 were reported in this outcome measure.

    Time frame: 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

29. Change From Baseline in Circulating Tumor Deoxyribonucleic Acid (ctDNA) Plasma Level: Phase 2

    Time frame: Baseline and up to End of Treatment

Baseline characteristics

Related links

• To obtain contact information for a study center near you, click here. ↗

Study documents

• Study protocol · Oct 20, 2025
• Statistical analysis plan · Jan 30, 2024

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: 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.