Clinical trial NCT06206837: A Study to Learn About Vepdegestrant When Given With PF-07220060 to People With Advanced or Metastatic Breast Cancer.
Official title: 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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
PHASE2
Conditions: Breast Cancer
Keywords: Proteolysis Targeting Chimera (PROTAC)
metastatic breast cancer
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
Collaborators: name: Arvinas Estrogen Receptor, Inc.
First posted: 2024-01-16
Enrollment: 65
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SEQUENTIAL
Intervention model description: 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.
Primary purpose: TREATMENT

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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Phase 1b: Number of Participants With Dose Limiting Toxicities
timeFrame: 28 days
measure: Phase 2: Percentage of Participants With Objective Response by investigator assessment
timeFrame: Up to approximately 1 year
Secondary outcomes:
measure: 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)
timeFrame: First study drug dose through a minimum of 28 Days After Last study drug administration
measure: 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)
timeFrame: First study drug dose through a minimum of 28 Days After Last study drug administration
measure: Phase 1b and Phase 2: Evaluation of Safety of Vepdegestrant in combination with PF-07220060 (number of participants with lab abnormalities - chemistry parameters)
timeFrame: First study drug dose through a minimum of 28 Days After Last study drug administration
measure: 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)
timeFrame: First study drug dose through a minimum of 28 Days After Last study drug administration
measure: 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)
timeFrame: First study drug dose through a minimum of 28 Days After Last study drug administration
measure: Phase 1b and Phase 2: Evaluation of Tolerability of Vepdegestrant in combination with PF-07220060 (number of participants with lab abnormalities- Hematology and coagulation parameters)
timeFrame: First study drug dose through a minimum of 28 Days After Last study drug administration
measure: Phase 1b and Phase 2: Evaluation of Tolerability of Vepdegestrant in combination with PF-07220060 (number of participants with lab abnormalities - chemistry parameters)
timeFrame: First study drug dose through a minimum of 28 Days After Last study drug administration
measure: Phase 1b and Phase 2: Evaluation of Tolerability of Vepdegestrant in combination with PF-07220060 (number of participants with changes from baseline for ECG parameters)
timeFrame: First study drug dose through a minimum of 28 Days After Last study drug administration
measure: Phase 1b: To evaluate antitumor activity of Vepdegestrant in combination with PF-07220060
timeFrame: Up to approximately 1 year
measure: Phase 1b and Phase 2: Duration of Response by investigator assessment.
timeFrame: Up to approximately 1 year
measure: Phase 1b and Phase2: Percentage of participants with Clinical Benefit Response by investigator assessment.
timeFrame: Up to approximately 1 year
measure: Phase 1b and Phase 2: Progression Free Survival by investigator assessment.
timeFrame: Up to approximately 1 year
measure: Phase 1b and Phase 2: Plasma concentrations of Vepdegestrant, ARV-473 and PF-07220060 when given in combination.
timeFrame: Phase 1b: Pre-dose Day 8; Pre-, 0.5, 1, 2, 4, 6, 8, 12h post-dose Day 15; Pre- and 4-8h post-dose 29; Pre- and 4-8h post-dose Day 43; Pre-dose Days 57, 113 and 169. Phase 2: Pre- and 4-8h post-dose Days 15, 29 and 43; Pre-dose Days 57, 113 and 169
measure: Phase 1b: Evaluation of the PK of Vepdegestrant and PF-07220060 when given in combination
timeFrame: Phase 1b (a cycle is 28 days): Pre-dose on Day 8 of Cycle 1; Pre-dose, 0.5, 1, 2, 4, 6, 8, 12h post-dose on Day 15 of Cycle 1; Pre-dose and 4-8h on Day 1 of Cycle 2; Pre-dose and 4-8h post-dose on Day 15 of Cycle 2; Pre-dose on Day 1 of Cycles 3, 5 and 7
measure: Phase 1b: Evaluation of the PK of Vepdegestrant and PF-07220060 when given in combination
timeFrame: Phase 1b (a cycle is 28 days): Pre-dose on Day 8 of Cycle 1; Pre-dose, 0.5, 1, 2, 4, 6, 8, 12h post-dose on Day 15 of Cycle 1; Pre-dose and 4-8h on Day 1 of Cycle 2; Pre-dose and 4-8h post-dose on Day 15 of Cycle 2; Pre-dose on Day 1 of Cycles 3, 5 and 7
measure: Phase 1b: Evaluation of the PK of Vepdegestrant and PF-07220060 when given in combination
timeFrame: Phase 1b (a cycle is 28 days): Pre-dose on Day 8 of Cycle 1; Pre-dose, 0.5, 1, 2, 4, 6, 8, 12h post-dose on Day 15 of Cycle 1; Pre-dose and 4-8h on Day 1 of Cycle 2; Pre-dose and 4-8h post-dose on Day 15 of Cycle 2; Pre-dose on Day 1 of Cycles 3, 5 and 7
measure: Phase 2:ctDNA plasma quantitative changes from pre-treatment
timeFrame: Phase 2 (each cycle is 28 days): Pre-dose on Day 1 of Cycles 1, 2 and 3 and after last treatment administration.
Other outcomes:
Locations:
city: Fayetteville
country: United States
facility: Highlands Oncology
state: Arkansas
city: Rogers
country: United States
facility: Highlands Oncology
state: Arkansas
city: Springdale
country: United States
facility: Highlands Oncology Group
state: Arkansas
city: Irvine
country: United States
facility: Hoag Health Center Irvine
state: California
city: Irvine
country: United States
facility: Hoag Hospital Irvine
state: California
city: Newport Beach
country: United States
facility: Hoag Memorial Hospital Presbyterian
state: California
city: Palo Alto
country: United States
facility: Stanford Cancer Center
state: California
city: Palo Alto
country: United States
facility: Stanford Cancer Institute - Clinical Trials Office
state: California
city: San Francisco
country: United States
facility: UCSF Medical Center at Mission Bay
state: California
city: Fort Collins
country: United States
facility: UCHealth Poudre Valley Hospital
state: Colorado
city: Fort Collins
country: United States
facility: UCHealth Harmony
state: Colorado
city: Greeley
country: United States
facility: UCHealth Greeley Hospital
state: Colorado
city: Loveland
country: United States
facility: UCHealth - Medical Center of the Rockies
state: Colorado
city: New Haven
country: United States
facility: Smilow Cancer Hospital - Yale New Haven Health
state: Connecticut
city: New Haven
country: United States
facility: Yale - New Haven Hospital - Yale Cancer Center
state: Connecticut
city: New Haven
country: United States
facility: Smilow Cancer Hospital Phase 1 Unit
state: Connecticut
city: Trumbull
country: United States
facility: Smilow Cancer Hospital - Trumbull
state: Connecticut
city: Grand Rapids
country: United States
facility: START Midwest
state: Michigan
city: Basking Ridge
country: United States
facility: MSK Basking Ridge
state: New Jersey
city: Middletown
country: United States
facility: MSK Monmouth
state: New Jersey
city: Montvale
country: United States
facility: MSK Bergen
state: New Jersey
city: Commack
country: United States
facility: MSK Commack
state: New York
city: Harrison
country: United States
facility: MSK Westchester
state: New York
city: New York
country: United States
facility: Rockefeller Outpatient Pavilion (53rd Street)
state: New York
city: New York
country: United States
facility: Evelyn H. Lauder Breast and Imaging Center (BAIC).
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Uniondale
country: United States
facility: MSK Nassau
state: New York
city: San Antonio
country: United States
facility: South Texas Accelerated Research Therapeutics (START)
state: Texas
city: Salt Lake City
country: United States
facility: Huntsman Cancer Institute
state: Utah
city: West Valley City
country: United States
facility: START Mountain Region
state: Utah
city: Edegem
country: Belgium
facility: Antwerp University Hospital
state: Antwerpen
city: Anderlecht
country: Belgium
facility: Institut Jules Bordet
state: Bruxelles-capitale, Région DE
city: Leuven
country: Belgium
facility: UZ Leuven
state: Vlaams-brabant
city: Kortrijk
country: Belgium
facility: AZ Groeninge Campus Kennedylaan
state: West-vlaanderen
city: Ottawa
country: Canada
facility: The Ottawa Hospital - General Campus
state: Ontario
city: Toronto
country: Canada
facility: Sunnybrook Research Institute
state: Ontario
city: Toronto
country: Canada
facility: Princess Margaret Cancer Centre
state: Ontario
city: Guangzhou
country: China
facility: Sun Yat-sen University Cancer Center
state: Guangdong
city: Wuhan
country: China
facility: Wuhan Union Hospital Cancer Center
state: Hubei
city: Xi'an
country: China
facility: The First Affiliated Hospital of Xi'an Jiaotong University
state: Shaanxi
city: Montpellier
country: France
facility: Institut Régional du Cancer Montpellier
state: Hérault
city: Saint Herblain
country: France
facility: Institut de Cancérologie de l'Ouest
state: Loire-atlantique
city: Marseille
country: France
facility: Institut Paoli-Calmettes
state: Provence-alpes-côte-d'azur
city: Kashiwa
country: Japan
facility: National Cancer Center Hospital East
state: Chiba
city: Yokohama
country: Japan
facility: Kanagawa cancer center
state: Kanagawa
city: Chuo-ku
country: Japan
facility: National Cancer Center Hospital
state: Tokyo
city: Shinagawa
country: Japan
facility: Showa University Hospital
state: Tokyo
city: Mayaguez
country: Puerto Rico
facility: BRCR Global - Mayaguez Administrative Office
city: Mayaguez
country: Puerto Rico
facility: BRCR Global - Mayagüez
city: Rio Piedras
country: Puerto Rico
facility: Pan American Center for Oncology Trials, LLC
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebron
state: Barcelona [barcelona]
city: Lleida
country: Spain
facility: Hospital Universitario Arnau de Vilanova de Lleida
state: Lleida [lérida]
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
state: Madrid, Comunidad DE
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen Del Rocio
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References: