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

NCT06206837 | Active Not Recruiting Phase 1 FDA Drug

• 3 other identifiers: C4891026TACTIVE-K2023-508130-33-00
• Study Type: interventional
• Target: 71
• Locations: 8 countries
• Sites: 58

Brief Summary

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.

Conditions

Breast Cancer

Keywords

Proteolysis Targeting Chimera (PROTAC); metastatic breast cancer

Outcome Measures

Primary Outcomes (2)

• Phase 1b: Number of Participants With Dose Limiting Toxicities

  Dose Limiting Toxicities (DLTs) rate for Vepdegestrant in combination with PF-07220060, estimated based on data from DLT-evaluable participants during the DLT observation period (Cycle 1).

  28 days

• Phase 2: Percentage of Participants With Objective Response by investigator assessment

  Objective response (OR) refers to confirmed complete response (CR) or partial response (PR) according to Response Evaluation Criteria in Solid Tumor (RECIST) version 1.1. as determined by investigator assessment.

  Up to approximately 1 year

Secondary Outcomes (17)

• Phase 1b and Phase 2: Evaluation of Safety of Vepdegestrant in combination with PF-07220060 (number of participants experiencing any AE, SAE, treatment-related AE and treatment-related SAE)

  First study drug dose through a minimum of 28 Days After Last study drug administration

• Phase 1b and Phase 2: Evaluation of Safety of Vepdegestrant in combination with PF-07220060 (number of participants with lab abnormalities - Hematology and coagulation parameters)

  First study drug dose through a minimum of 28 Days After Last study drug administration

• Phase 1b and Phase 2: Evaluation of Safety of Vepdegestrant in combination with PF-07220060 (number of participants with lab abnormalities - chemistry parameters)

  First study drug dose through a minimum of 28 Days After Last study drug administration

• Phase 1b and Phase 2: Evaluation of Safety of Vepdegestrant in combination with PF-07220060 (number of participants with changes from baseline for ECG parameters)

  First study drug dose through a minimum of 28 Days After Last study drug administration

• Phase 1b and Phase 2: Evaluation of Tolerability of Vepdegestrant in combination with PF-07220060 (number of participants experiencing any AE, SAE, treatment-related AE and treatment-related SAE)

  First study drug dose through a minimum of 28 Days After Last study drug administration

Study Arms (1)

vepdegestrant in combination with PF-07220060

EXPERIMENTAL

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

PF-07220060 DRUG

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

vepdegestrant in combination with PF-07220060

vepdegestrant DRUG

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

vepdegestrant in combination with PF-07220060

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• , 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• Pfizer: lead
• Arvinas Estrogen Receptor, Inc.: collaborator

Study Sites (58)

Highlands Oncology

Fayetteville, Arkansas, 72703, United States

Location

Highlands Oncology

Rogers, Arkansas, 72758, United States

Location

Highlands Oncology Group

Springdale, Arkansas, 72762, United States

Location

Hoag Health Center Irvine

Irvine, California, 92618, United States

Location

Hoag Hospital Irvine

Irvine, California, 92618, United States

Location

Hoag Memorial Hospital Presbyterian

Newport Beach, California, 92663, United States

Location

Stanford Cancer Center

Palo Alto, California, 94304, United States

Location

Stanford Cancer Institute - Clinical Trials Office

Palo Alto, California, 94304, United States

Location

Stanford Women's Cancer Center

Palo Alto, California, 94304, United States

Location

UCSF Medical Center at Mission Bay

San Francisco, California, 94158, United States

Location

UCHealth Poudre Valley Hospital

Fort Collins, Colorado, 80524, United States

Location

UCHealth Harmony

Fort Collins, Colorado, 80528, United States

Location

UCHealth Greeley Hospital

Greeley, Colorado, 80634, United States

Location

UCHealth - Medical Center of the Rockies

Loveland, Colorado, 80538, United States

Location

Smilow Cancer Hospital - Yale New Haven Health

New Haven, Connecticut, 06510, United States

Location

Yale - New Haven Hospital - Yale Cancer Center

New Haven, Connecticut, 06510, United States

Location

Smilow Cancer Hospital Phase 1 Unit

New Haven, Connecticut, 06511, United States

Location

Smilow Cancer Hospital - Trumbull

Trumbull, Connecticut, 06611, United States

Location

START Midwest

Grand Rapids, Michigan, 49546, United States

Location

MSK Basking Ridge

Basking Ridge, New Jersey, 07920, United States

Location

MSK Monmouth

Middletown, New Jersey, 07748, United States

Location

MSK Bergen

Montvale, New Jersey, 07645, United States

Location

MSK Commack

Commack, New York, 11725, United States

Location

MSK Westchester

Harrison, New York, 10604, United States

Location

Rockefeller Outpatient Pavilion (53rd Street)

New York, New York, 10022, United States

Location

Evelyn H. Lauder Breast and Imaging Center (BAIC).

New York, New York, 10065, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

MSK Nassau

Uniondale, New York, 11553, United States

Location

START San Antonio

San Antonio, Texas, 78229, United States

Location

University of Utah, Farmington Health Center

Farmington, Utah, 84025, United States

Location

University of Utah, Sugar House Health Center

Salt Lake City, Utah, 84106, United States

Location

Huntsman Cancer Institute

Salt Lake City, Utah, 84112, United States

Location

South Jordan Health Center - University of Utah

South Jordan, Utah, 84106, United States

Location

START Mountain Region

West Valley City, Utah, 84119, United States

Location

Antwerp University Hospital

Edegem, Antwerpen, 2650, Belgium

Location

Institut Jules Bordet

Anderlecht, Bruxelles-capitale, Région de, 1070, Belgium

Location

UZ Leuven

Leuven, Vlaams-brabant, 3000, Belgium

Location

AZ Groeninge Campus Kennedylaan

Kortrijk, West-vlaanderen, 8500, Belgium

Location

The Ottawa Hospital - General Campus

Ottawa, Ontario, K1H 8L6, Canada

Location

Sunnybrook Research Institute

Toronto, Ontario, M4N 3M5, Canada

Location

Princess Margaret Cancer Centre

Toronto, Ontario, M5G 2M9, Canada

Location

Sun Yat-sen University Cancer Center

Guangzhou, Guangdong, 510060, China

Location

Wuhan Union Hospital Cancer Center

Wuhan, Hubei, 430023, China

Location

The First Affiliated Hospital of Xi'an Jiaotong University

Xi'an, Shaanxi, 710061, China

Location

Institut Régional du Cancer Montpellier

Montpellier, Hérault, 34298, France

Location

Institut de Cancérologie de l'Ouest

Saint-Herblain, Loire-atlantique, 44805, France

Location

Institut Paoli-Calmettes

Marseille, Provence-Alpes-Côte d'Azur Region, 13273, France

Location

National Cancer Center Hospital East

Kashiwa, Chiba, 277-8577, Japan

Location

Kanagawa cancer center

Yokohama, Kanagawa, 2418515, Japan

Location

National Cancer Center Hospital

Chuo-ku, Tokyo, 104-0045, Japan

Location

Showa Medical University Hospital

Tokyo, 142-8666, Japan

Location

BRCR Global - Mayaguez Administrative Office

Mayagüez, 00680, Puerto Rico

Location

BRCR Global - Mayagüez

Mayagüez, 00682, Puerto Rico

Location

Pan American Center for Oncology Trials, LLC

Rio Piedras, 00935, Puerto Rico

Location

Hospital Universitari Vall d'Hebron

Barcelona, Barcelona [barcelona], 08035, Spain

Location

Hospital Universitario Arnau de Vilanova de Lleida

Lleida, Lleida [lérida], 25198, Spain

Location

Hospital Universitario 12 de Octubre

Madrid, Madrid, Comunidad de, 28041, Spain

Location

Hospital Universitario Virgen Del Rocio

Seville, 41013, Spain

Location

Related Links

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

MeSH Terms

Conditions

Breast Neoplasms

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Study Officials

• Pfizer CT.gov Call Center

  Pfizer

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Phase 1b will use an escalation/de-escalation approach to determine the recommended phase 2 dose (RP2D) of vepdegestrant when administered in combination with PF-07220060. The decision to escalate the starting dose level of vepdegestrant will be using mTPI-2 decision criteria based on the number of dose limiting toxicity (DLT)-evaluable participants and the number of DLTs in those participants during the DLT observation period (Cycle 1). Phase 2 will further evaluate the preliminary antitumor activity and safety of the combination RP2D.

Study Record Dates

• First Submitted: December 13, 2023
• First Posted: January 16, 2024
• Study Start: February 19, 2024
• Primary Completion: September 5, 2025
• Study Completion (Estimated): September 7, 2026
• Last Updated: February 27, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will share

Locations

US (34); BE (4); ES (4); CN (3); PR (3); FR (3); CA (3); JP (4)