Un estudio para conocer el vepdegestrant cuando se administra con PF-07220060 a personas con cáncer de mama avanzado o metastásico.
UN ESTUDIO INTERVENCIONAL DE SEGURIDAD Y EFICACIA FASE 1B/2, DE ETIQUETA ABIERTA PARA INVESTIGAR LA TOLERABILIDAD, PK Y ACTIVIDAD ANTITUMORAL DEL VEPDEGESTRANTE (ARV-471/PF-07850327), UNA QUIMERA DIRIGIDA A LA PROTEÓLISIS ORAL, EN COMBINACIÓN CON PF-07220060 EN PARTICIPANTES DE EDAD 18 AÑOS Y MAYORES CON CÁNCER DE MAMA AVANZADO O METASTÁSICO ER+/HER2-
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.
Descripción general del estudio
Estado
Condiciones
Intervención / Tratamiento
Descripción detallada
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.
Tipo de estudio
Inscripción (Actual)
Fase
- Fase 2
- Fase 1
Contactos y Ubicaciones
Ubicaciones de estudio
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Antwerpen
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Edegem, Antwerpen, Bélgica, 2650
- Antwerp University Hospital
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Bruxelles-capitale, Région de
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Anderlecht, Bruxelles-capitale, Région de, Bélgica, 1070
- Institut Jules Bordet
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Vlaams-brabant
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Leuven, Vlaams-brabant, Bélgica, 3000
- UZ Leuven
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West-vlaanderen
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Kortrijk, West-vlaanderen, Bélgica, 8500
- AZ Groeninge Campus Kennedylaan
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Ontario
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Ottawa, Ontario, Canadá, K1H 8L6
- The Ottawa Hospital - General Campus
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Toronto, Ontario, Canadá, M5G 2M9
- Princess Margaret Cancer Centre
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Toronto, Ontario, Canadá, M4N 3M5
- Sunnybrook Research Institute
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Seville, España, 41013
- Hospital Universitario Virgen Del Rocio
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Barcelona [barcelona]
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Barcelona, Barcelona [barcelona], España, 08035
- Hospital Universitari Vall d'Hebron
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Lleida [lérida]
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Lleida, Lleida [lérida], España, 25198
- Hospital Universitario Arnau de Vilanova de Lleida
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Madrid, Comunidad de
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Madrid, Madrid, Comunidad de, España, 28041
- Hospital Universitario 12 de Octubre
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Arkansas
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Fayetteville, Arkansas, Estados Unidos, 72703
- Highlands Oncology
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Rogers, Arkansas, Estados Unidos, 72758
- Highlands Oncology
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Springdale, Arkansas, Estados Unidos, 72762
- Highlands Oncology Group
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California
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Irvine, California, Estados Unidos, 92618
- Hoag Hospital Irvine
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Irvine, California, Estados Unidos, 92618
- Hoag Health Center Irvine
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Newport Beach, California, Estados Unidos, 92663
- Hoag Memorial Hospital Presbyterian
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Palo Alto, California, Estados Unidos, 94304
- Stanford Cancer Center
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Palo Alto, California, Estados Unidos, 94304
- Clinical and Translational Research Unit (CTRU)
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Palo Alto, California, Estados Unidos, 94304
- Stanford Cancer Institute - Clinical Trials Office
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San Francisco, California, Estados Unidos, 94158
- UCSF Medical Center at Mission Bay
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Colorado
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Fort Collins, Colorado, Estados Unidos, 80524
- UCHealth Poudre Valley Hospital
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Fort Collins, Colorado, Estados Unidos, 80528
- UCHealth Harmony
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Greeley, Colorado, Estados Unidos, 80634
- UCHealth Greeley Hospital
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Loveland, Colorado, Estados Unidos, 80538
- UCHealth - Medical Center of the Rockies
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Connecticut
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New Haven, Connecticut, Estados Unidos, 06511
- Smilow Cancer Hospital Phase 1 Unit
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New Haven, Connecticut, Estados Unidos, 06510
- Smilow Cancer Hospital - Yale New Haven Health
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New Haven, Connecticut, Estados Unidos, 06510
- Yale - New Haven Hospital - Yale Cancer Center
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Trumbull, Connecticut, Estados Unidos, 06611
- Smilow Cancer Hospital - Trumbull
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Michigan
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Grand Rapids, Michigan, Estados Unidos, 49546
- START Midwest
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New Jersey
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Basking Ridge, New Jersey, Estados Unidos, 07920
- MSK Basking Ridge
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Middletown, New Jersey, Estados Unidos, 07748
- MSK Monmouth
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Montvale, New Jersey, Estados Unidos, 07645
- MSK Bergen
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New York
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Commack, New York, Estados Unidos, 11725
- MSK Commack
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Harrison, New York, Estados Unidos, 10604
- MSK Westchester
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New York, New York, Estados Unidos, 10065
- Memorial Sloan Kettering Cancer Center
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New York, New York, Estados Unidos, 10022
- Rockefeller Outpatient Pavilion (53rd Street)
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New York, New York, Estados Unidos, 10065
- Evelyn H. Lauder Breast and Imaging Center (BAIC).
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Uniondale, New York, Estados Unidos, 11553
- MSK Nassau
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Texas
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San Antonio, Texas, Estados Unidos, 78229
- START San Antonio
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Utah
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Farmington, Utah, Estados Unidos, 84025
- University of Utah, Farmington Health Center
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Salt Lake City, Utah, Estados Unidos, 84112
- Huntsman Cancer Institute
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Salt Lake City, Utah, Estados Unidos, 84106
- University of Utah, Sugar House Health Center
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South Jordan, Utah, Estados Unidos, 84106
- South Jordan Health Center - University of Utah
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West Valley City, Utah, Estados Unidos, 84119
- START Mountain Region
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Hérault
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Montpellier, Hérault, Francia, 34298
- Institut Régional du Cancer Montpellier
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Loire-atlantique
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Saint-Herblain, Loire-atlantique, Francia, 44805
- Institut de Cancérologie de l'Ouest
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Provence-Alpes-Côte d'Azur Region
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Marseille, Provence-Alpes-Côte d'Azur Region, Francia, 13273
- Institut Paoli-Calmettes
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Tokyo, Japón, 142-8666
- Showa Medical University Hospital
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Chiba
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Kashiwa, Chiba, Japón, 277-8577
- National Cancer Center Hospital East
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Kanagawa
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Yokohama, Kanagawa, Japón, 2418515
- Kanagawa cancer center
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Tokyo
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Chuo-ku, Tokyo, Japón, 104-0045
- National Cancer Center Hospital
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Guangdong
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Guangzhou, Guangdong, Porcelana, 510060
- Sun Yat-sen University Cancer Center
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Hubei
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Wuhan, Hubei, Porcelana, 430023
- Wuhan Union Hospital Cancer Center
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Shaanxi
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Xi'an, Shaanxi, Porcelana, 710061
- The First Affiliated Hospital of Xi'an Jiaotong University
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Mayagüez, Puerto Rico, 00680
- BRCR Global - Mayaguez Administrative Office
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Mayagüez, Puerto Rico, 00682
- BRCR Global - Mayagüez
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Rio Piedras, Puerto Rico, 00935
- Pan American Center for Oncology Trials, LLC
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Criterios de participación
Criterio de elegibilidad
Edades elegibles para estudiar
Acepta Voluntarios Saludables
Géneros elegibles para el estudio
Descripción
Inclusion Criteria:
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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).
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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.
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Participant with only non-measurable lesion (Phase1b) or at least 1 measurable lesion as defined by RECIST v1.1. (Phase2) are eligible.
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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
Plan de estudios
¿Cómo está diseñado el estudio?
Detalles de diseño
- Propósito principal: Tratamiento
- Asignación: N / A
- Modelo Intervencionista: Asignación Secuencial
- Enmascaramiento: Ninguno (etiqueta abierta)
Armas e Intervenciones
Grupo de participantes/brazo |
Intervención / Tratamiento |
|---|---|
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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 |
Daily oral dosages of vepdegestrant continuously, dose escalation/de-escalation in Phase 1b until recommended phase 2 dose (RP2D) determined, cycles lasting 28 days
Otros nombres:
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 |
¿Qué mide el estudio?
Medidas de resultado primarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
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Number of Participants With Dose-Limiting Toxicities (DLTs): Phase 1b
Periodo de tiempo: Cycle 1 (28 days)
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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)
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Percentage of Participants With Confirmed Objective Response (OR) by Derived Investigator Assessment: Phase 2
Periodo de tiempo: 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)
|
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)
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Medidas de resultado secundarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
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Number of Participants With Treatment Emergent Adverse Events (TEAEs), Treatment Emergent Serious Adverse Events (TESAEs) and Treatment Related TEAEs: Phase 1b
Periodo de tiempo: From the date of first dose of study treatment combination through study completion
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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
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Number of Participants With Laboratory Abnormalities: Phase 1b
Periodo de tiempo: From the date of first dose of study treatment combination through study completion
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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
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Number of Participants With Electrocardiogram (ECG) Abnormalities: Phase 1b
Periodo de tiempo: From the date of first dose of study treatment combination through study completion
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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
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Percentage of Participants With Confirmed OR by Derived Investigator Assessment: Phase 1b
Periodo de tiempo: From the date of first dose of study treatment combination through study completion
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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
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Duration of Response (DOR) by Derived Investigator Assessment: Phase 1b
Periodo de tiempo: From the date of first dose of study treatment combination through study completion
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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
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Clinical Benefit Response (CBR) by Derived Investigator Assessment: Phase 1b
Periodo de tiempo: From the date of first dose of study treatment combination through study completion
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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
|
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Progression Free Survival (PFS) by Derived Investigator Assessment: Phase 1b
Periodo de tiempo: From the date of first dose of study treatment combination through study completion
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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
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Plasma Concentration of Vepdegestrant (ARV-471) and Its Epimer ARV-473: Phase 1b
Periodo de tiempo: 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
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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
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Plasma Concentration of PF-07220060: Phase 1b
Periodo de tiempo: 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
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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
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Steady State Maximum Observed Plasma Concentration (Cmax,ss) of Vepdegestrant (ARV-471) and Its Epimer ARV-473: Phase 1b
Periodo de tiempo: Predose (0 hours), 0.5, 1, 2, 4, 6, 8, and 12 hours post dose on Cycle 1 Day 15
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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
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Cmax,ss of PF-07220060: Phase 1b
Periodo de tiempo: Predose (0 hours), 0.5, 1, 2, 4, 6, 8, and 12 hours post dose on Cycle 1 Day 15
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Predose (0 hours), 0.5, 1, 2, 4, 6, 8, and 12 hours post dose on Cycle 1 Day 15
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Steady State Time to Maximum Plasma Concentration (Tmax,ss) of Vepdegestrant (ARV-471) and Its Epimer ARV-473: Phase 1b
Periodo de tiempo: Predose (0 hours), 0.5, 1, 2, 4, 6, 8, and 12 hours post dose on Cycle 1 Day 15
|
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
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Tmax,ss of PF-07220060: Phase 1b
Periodo de tiempo: Predose (0 hours), 0.5, 1, 2, 4, 6, 8, and 12 hours post dose on Cycle 1 Day 15
|
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
|
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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
Periodo de tiempo: Predose (0 hours), 0.5, 1, 2, 4, 6, 8, and 12 hours post dose on Cycle 1 Day 15
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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
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AUClast,ss of PF-07220060: Phase 1b
Periodo de tiempo: Predose (0 hours), 0.5, 1, 2, 4, 6, 8, and 12 hours post dose on Cycle 1 Day 15
|
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
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Apparent Total Clearance (CL/F) of Vepdegestrant (ARV-471): Phase 1b
Periodo de tiempo: Predose (0 hours), 0.5, 1, 2, 4, 6, 8, and 12 hours post dose on Cycle 1 Day 15
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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
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CL/F of PF-07220060: Phase 1b
Periodo de tiempo: Predose (0 hours), 0.5, 1, 2, 4, 6, 8, and 12 hours post dose on Cycle 1 Day 15
|
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
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Apparent Volume of Distribution (Vz/F) of PF-07220060: Phase 1b
Periodo de tiempo: Predose (0 hours), 0.5, 1, 2, 4, 6, 8, and 12 hours post dose on Cycle 1 Day 15
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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
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Terminal Half-Life (t1/2) of PF-07220060: Phase 1b
Periodo de tiempo: Predose (0 hours), 0.5, 1, 2, 4, 6, 8, and 12 hours post dose on Cycle 1 Day 15
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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
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DOR by Derived Investigator Assessment: Phase 2
Periodo de tiempo: From the date of first dose of study treatment combination through study completion
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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
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Percentage of Participants With CBR by Derived Investigator Assessment: Phase 2
Periodo de tiempo: From the date of first dose of study treatment combination through study completion
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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
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PFS by Derived Investigator Assessment: Phase 2
Periodo de tiempo: From the date of first dose of study treatment combination through study completion
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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
Periodo de tiempo: From the date of first dose of study treatment combination through study completion
|
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
Periodo de tiempo: From the date of first dose of study treatment combination through study completion
|
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
Periodo de tiempo: From the date of first dose of study treatment combination through study completion
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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
Periodo de tiempo: From the date of first dose of study treatment combination through study completion
|
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
Periodo de tiempo: 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 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
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Plasma Concentration of PF-07220060: Phase 2
Periodo de tiempo: 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
|
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
|
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Change From Baseline in Circulating Tumor Deoxyribonucleic Acid (ctDNA) Plasma Level: Phase 2
Periodo de tiempo: Baseline and up to End of Treatment
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Baseline and up to End of Treatment
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Colaboradores e Investigadores
Patrocinador
Colaboradores
Investigadores
- Director de estudio: Pfizer CT.gov Call Center, Pfizer
Publicaciones y enlaces útiles
Fechas de registro del estudio
Fechas importantes del estudio
Inicio del estudio (Actual)
Finalización primaria (Actual)
Finalización del estudio (Estimado)
Fechas de registro del estudio
Enviado por primera vez
Primero enviado que cumplió con los criterios de control de calidad
Publicado por primera vez (Actual)
Actualizaciones de registros de estudio
Última actualización publicada (Actual)
Última actualización enviada que cumplió con los criterios de control de calidad
Última verificación
Más información
Términos relacionados con este estudio
Términos MeSH relevantes adicionales
Otros números de identificación del estudio
- C4891026
- 2023-508130-33-00 (Identificador de registro: CTIS (EU))
- TACTIVE-K (Otro identificador: Alias Study Number)
- 2023 (Subvención/contrato del NIH de EE. UU.)
Plan de datos de participantes individuales (IPD)
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Descripción del plan IPD
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.
Información sobre medicamentos y dispositivos, documentos del estudio
Estudia un producto farmacéutico regulado por la FDA de EE. UU.
Estudia un producto de dispositivo regulado por la FDA de EE. UU.
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