TACTIVE-U: A Study to Learn About the Study Medicine (Vepdegestrant) When Given With Other Medicines in People With Advanced or Metastatic Breast Cancer (Sub-Study A)

TACTIVE-U: An Interventional Safety and Efficacy Phase 1b/2, Open-label Umbrella Study to Investigate Tolerability, pk, and Antitumor Activity of Vepdegestrant (ARV-471/PF-07850327), an Oral Proteolysis Targeting Chimera, in Combination With Other Anticancer Treatments in Participants Aged 18 Years and Over With ER+ Advanced or Metastatic Breast Cancer, Sub-study A (ARV-471 in Combination With Abemaciclib)

The purpose of this clinical trial is to learn about the safety and effects of the study medicine (called ARV-471) when given together with other medicines for the potential treatment of advanced or metastatic breast cancer.

This study is seeking participants who have breast cancer that:

• is advanced, may have spread to other organs (metastatic) and cannot be fully treated by surgery or radiation therapy
• is sensitive to hormonal therapy (it is called estrogen receptor positive); and
• is no longer responding to previous treatments This study is divided into separate sub-studies.

For Sub-Study A:

All participants will receive ARV-471 and a medicine called abemaciclib. ARV-471 will be given by mouth, at home, 1 time a day. Abemaciclib will be given by mouth, at home, 2 times a day. We will examine the experiences of people receiving the study medicines. This will help us determine if the study medicines are safe and effective.

Participants will continue to take ARV-471 and abemaciclib 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: Recruiting
• Conditions: Breast Cancer
• Intervention / Treatment: Drug: ARV-471; Drug: Abemaciclib

Detailed Description

C4891006 is a sub-study from the Umbrella platform, TACTIVE-U, comprising multiple sub-studies that independently evaluate ARV-471 in participants with Estrogen Receptor Positive (ER+) Advanced or Metastatic Breast Cancer (A/MBC). ARV-471 will act as the backbone therapy given in combination with other anticancer agents thought to have clinical relevance in ER+ breast cancer.

• Study Type: Interventional
• Enrollment (Estimated): 40
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Pfizer CT.gov Call Center; Phone Number: 1-800-718-1021; Email: ClinicalTrials.gov_Inquiries@pfizer.com

Study Locations

• Canada
  • British Columbia
    • Vancouver, British Columbia, Canada, V5Z 4E6
      • Recruiting
      • BC Cancer Vancouver
    • Vancouver, British Columbia, Canada, V5Z 1H7
      • Recruiting
      • BC Cancer Vancouver
  • Ontario
    • Ottawa, Ontario, Canada, K1H 8L6
      • Recruiting
      • The Ottawa Hospital - General Campus
    • Toronto, Ontario, Canada, M4N 3M5
      • Recruiting
      • Sunnybrook Research Institute
  • Quebec
    • Chicoutimi, Quebec, Canada, G7H 5H6
      • Recruiting
      • CIUSSS- saguenay-Lac-Saint-Jean
    • Montreal, Quebec, Canada, H3T 1E2
      • Recruiting
      • Jewish General Hospital
• Italy
  • Ancona, Italy, 60126
    • Not yet recruiting
    • Azienda Ospedaliero Universitaria delle Marche
  • Padova, Italy, 35128
    • Not yet recruiting
    • Istituto Oncologico Veneto IRCCS
  • Campania
    • Napoli, Campania, Italy, 80131
      • Not yet recruiting
      • Istituto Nazionale Tumori IRCCS Fondazione Pascale
  • Catania
    • Misterbianco, Catania, Italy, 95045
      • Not yet recruiting
      • Humanitas Istituto Clinico Catanese
  • Lazio
    • Roma, Lazio, Italy, 00168
      • Not yet recruiting
      • Fondazione Policlinico Universitario Agostino Gemelli IRCCS - Università Cattolica del Sacro Cuore
  • Lombardia
    • Monza, Lombardia, Italy, 20900
      • Not yet recruiting
      • Fondazione IRCCS San Gerardo dei Tintori
  • Torino
    • Candiolo, Torino, Italy, 10060
      • Not yet recruiting
      • Istituto di Candiolo IRCCS - Fondazione del Piemonte per l'Oncologia
• Spain
  • Madrid, Spain, 28007
    • Recruiting
    • Hospital General Universitario Gregorio Marañón
  • Sevilla, Spain, 41013
    • Recruiting
    • Hospital Universitario Virgen del Rocío
  • Barcelona [barcelona]
    • Barcelona, Barcelona [barcelona], Spain, 08035
      • Recruiting
      • Hospital Universitari Vall d'Hebron
  • Catalunya [cataluña]
    • Barcelona, Catalunya [cataluña], Spain, 08028
      • Recruiting
      • Hospital Universitari Dexeus
  • Madrid, Comunidad DE
    • Madrid, Madrid, Comunidad DE, Spain, 28041
      • Recruiting
      • Hospital Universitario 12 de Octubre
    • Madrid, Madrid, Comunidad DE, Spain, 28027
      • Recruiting
      • Clinica Universidad de Navarra
  • Navarra
    • Pamplona, Navarra, Spain, 31008
      • Recruiting
      • Clinica Universidad de Navarra
• United States
  • California
    • Palo Alto, California, United States, 94304
      • Recruiting
      • Stanford Women's Cancer Center
    • Palo Alto, California, United States, 94304
      • Not yet recruiting
      • Stanford Women's Cancer Center
    • San Francisco, California, United States, 94158
      • Recruiting
      • UCSF Medical Center at Mission Bay
  • Florida
    • Tampa, Florida, United States, 33612
      • Not yet recruiting
      • Moffitt Cancer Center
    • Tampa, Florida, United States, 33612
      • Not yet recruiting
      • Moffitt Cancer Center, Richard M. Shulze Family Foundation Outpatient Center
    • Tampa, Florida, United States, 33607
      • Not yet recruiting
      • Moffitt Cancer Center - International Plaza
  • Illinois
    • Shiloh, Illinois, United States, 62269
      • Recruiting
      • Siteman Cancer Center - WUPI
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Recruiting
      • Massachusetts General Hospital
    • Boston, Massachusetts, United States, 02215
      • Not yet recruiting
      • Dana-Farber Cancer Institute
    • Boston, Massachusetts, United States, 02115
      • Not yet recruiting
      • Brigham and Women's Hospital
    • Newton, Massachusetts, United States, 02459
      • Not yet recruiting
      • Dana-Farber Cancer Institute - Chestnut Hill
  • Missouri
    • Creve Coeur, Missouri, United States, 63141
      • Recruiting
      • Siteman Cancer Center - West County
    • Florissant, Missouri, United States, 63031
      • Recruiting
      • Siteman Cancer Center - North County
    • Saint Louis, Missouri, United States, 63110
      • Recruiting
      • Washington University School of Medicine
    • Saint Louis, Missouri, United States, 63110
      • Recruiting
      • Barnes-Jewish Hospital
    • Saint Louis, Missouri, United States, 63110
      • Recruiting
      • Washington University
    • Saint Louis, Missouri, United States, 63129
      • Recruiting
      • Siteman Cancer Center - South County
    • Saint Louis, Missouri, United States, 63110
      • Recruiting
      • Washington University School of Medicine - Siteman Cancer Center
    • Saint Peters, Missouri, United States, 63376
      • Recruiting
      • Siteman Cancer Center - St Peters
  • Texas
    • Houston, Texas, United States, 77030
      • Recruiting
      • University of Texas MD Anderson Cancer Center
    • Houston, Texas, United States, 77030
      • Recruiting
      • U.T. MD Anderson Cancer Center
    • Houston, Texas, United States, 77030
      • Recruiting
      • U.T. MD Anderson Cancer Center, Investigational Pharmacy Services - Unit 376

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• histological or cytological diagnosis of ER+ and HER2- advanced/metastatic breast cancer that is not amendable to surgical resection with curative intent (≥1% ER+ stained cells on the most recent tumor biopsy).
• prior anticancer therapies: at least 1 and no more than 2 lines of prior therapies for advanced/metastatic disease; 1 line of any CDK4/6 inhibitor-based regimen is required (independent of the setting eg, adjuvant or advanced/metastatic)
• at least 1 measurable lesion as defined by RECIST v1.1.
• ECOG PS ≤1.

Exclusion Criteria:

• visceral crisis at risk of life-threatening complications in the short term
• known history of drug-induced pneumonitis or other significant symptomatic deterioration of lung functions.
• newly diagnosed brain metastases, or symptomatic 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 14 days prior to enrollment in the 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
• impaired cardiovascular function or clinically significant cardiovascular diseases
• concurrent administration of medications, food, or herb supplements that are strong inhibitors and strong/moderate inducers of CYP3A 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: ARV-471 in combination with Abemaciclib; ARV-471 administered orally once daily (QD) and Abemaciclib orally twice daily (BID) on 28-day cycle	Drug: ARV-471; Daily oral dosages of ARV-471 continuously, dose escalation/de-escalation in Phase 1b until the recommended phase 2 dose (RP2D) determined, cycles lasting 28 days; Other Names: vepdegestrant, PF-07850327; Drug: Abemaciclib; Daily oral dosages of Abemaciclib continuously, cycles lasting 28 days

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Phase 1b: number of participants with dose limiting toxicities	Dose Limiting Toxicities rate for ARV-471 in combination with abemaciclib, estimated based on data from DLT-evaluable participants during the DLT observation period (Cycle 1 [28 days]).	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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Phase 1b and Phase2: Percentage of participants with Clinical Benefit Response by investigator assessment.	Clinical Benefit Response (CBR) is defined as the proportion of participants with Best Overall Response of confirmed CR or PR at any time, or Stable Disease (SD) ≥24 weeks	Up to approximately 1 year
Phase 1b and Phase 2: Progression Free Survival by investigator assessment.	Progression Free Survival (PFS) is 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 occurs first.	Up to approximately 1 year
Phase 2: Overall Survival	Overall Survival (OS) is defined as the time from the date of first dose of study interventions to the date of death due to any cause	Through study completion, up to approximately 3 year
Phase 1b and Phase 2: number of participants experiencing any AE, SAE, Treatment Related SAE	An adverse event (AE) were any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. An SAE is any untoward medical occurrence that, at any dose: resulted in death; required inpatient hospitalization or prolongation of existing hospitalization; was life-threatening; resulted in persistent or significant disability/ incapacity; congenital anomaly/birth defect and other important medical events. Treatment-related AE is any untoward medical occurrence attributed to study drug in a participant who received study drug. AEs were graded by the investigator according to the Common Terminology Criteria for Adverse Events (CTCAE version 5.0) and coded using MedDRA were reported. Grade 1=mild; Grade 2=moderate; Grade 3=severe and Grade 4=life-threatening or disabling and grade 5=death.	Up to 28 days after last dose of study treatment
Phase 1b and Phase 2: number of participants with lab abnormalities - Hematology and coagulation parameters	Blood samples were collected for the analysis of following hematology and coagulation parameters: hemoglobin [g/L], platelets, leukocytes, neutrophils, lymphocytes, monocytes, eosinophils and basophils [10^9/L]; partial thromboplastin time prolonged, international normalized ratio increased, prothrombin time. Number of participants with hematological and coagulation abnormalities by grade as per CTCAE version 5.0 were reported. Grade 1=mild; Grade 2=moderate; Grade 3=severe and Grade 4=life-threatening or disabling and grade 5=death. For laboratory tests without CTCAE grade definitions, results will be categorized as normal, abnormal, or not done.	Up to 28 days after last dose of study treatment
Phase 1b and Phase 2: number of participants with lab abnormalities - chemistry parameters	Blood samples were collected for analysis of clinical chemistry parameters. These included: alanine aminotransferase, alkaline phosphatase, aspartate aminotransferase, [international unit per liter (IU/L)] ; Lipase and amilase [IU/L] (limited to cycle1 only); Albumin, bilirubin, urea ,calcium, creatinine, glucose, magnesium, phosphate, uric acid, chloride, potassium and sodium [millimol per liter (mmol/L)]; eGFR [milliliter per minute (ml/min)]. Number of participants with blood chemistry abnormalities by grade as per CTCAE version 5.0 were reported. Grade 1=mild; Grade 2=moderate; Grade 3=severe and Grade 4=life-threatening or disabling and grade 5=death. For laboratory tests without CTCAE grade definitions, results will be categorized as normal, abnormal, or not done.	Up to 28 days after last dose of study treatment
Phase 1b: 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
Phase 1b and Phase 2: duration of response by investigator assessment.	Duration of Response (DoR) is defined for participants with confirmed OR (CR or PR) as the time from the first documentation of OR to the first documentation of objective tumor progression or to death due to any cause, whichever occurs first.	Up to approximately 1 year
Phase 2:ctDNA plasma quantitative changes from pre-treatment	To assess changes from baseline levels in plasma circulating DNA (ctDNA) with treatment and to evaluate potential predictability of their associations with clinical outcome	Day 1, 29 and 57 and End of Treatment (an average of 1 year)
Phase 1b: Area Under the Curve from Time Zero to end of dosing interval Evaluation of abemaciclib with or without ARV-471	Exposure (AUCtau) of abemaciclib with and without co-administration of ARV-471	Phase 1b: pre-dose Day -1, 1, 15, 29, 43, 57, 113, 169; 1, 2, 4, 6, 8 hours post dose on Day -1 and 15; post dose Day 29 and 43
Phase 1b: Maximum Observed Plasma Concentration (Cmax) of abemaciclib with or without ARV-471	Concentration (Cmax) of abemaciclib with and without co-administration of ARV-471	Phase 1b: pre-dose Day -1, 1, 15, 29, 43, 57, 113, 169; 1, 2, 4, 6, 8 hours post dose on Day -1 and 15; post dose Day 29 and 43
Phase 1b and Phase 2: Maximum Observed Plasma Concentration (Cmax) of ARV-471	Plasma concentration of ARV-471	Phase 1b: pre-dose Day 1, 15, 29, 43, 57, 113, 169; 1, 2, 4, 6, 8 hours post dose on Day 15; post dose Day 29 and 43. Phase 2: pre and post dose Day 15, 29 and 43; pre - dose Day 57, 113 and 169
Phase 1b and Phase 2: Maximum Observed Plasma Concentration (Cmax) of abemaciclib	Plasma concentration of abemaciclib	Phase 1b: pre-dose Day -1, 1, 15, 29, 43, 57, 113, 169; 1, 2, 4, 6, 8 hours post dose on Day -1 and 15; post dose Day 29, 43 and 57 Phase 2: pre and post dose Day 15, 29 and 43; pre - dose Day 57, 113 and 169

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

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

Study record dates

Study Major Dates

• Study Start (Actual): February 23, 2023
• Primary Completion (Estimated): December 31, 2025
• Study Completion (Estimated): December 31, 2025

Study Registration Dates

• First Submitted: August 25, 2022
• First Submitted That Met QC Criteria: September 17, 2022
• First Posted (Actual): September 21, 2022

Study Record Updates

• Last Update Posted (Actual): June 6, 2024
• Last Update Submitted That Met QC Criteria: June 5, 2024
• Last Verified: June 1, 2024

More Information

Terms related to this study

• Keywords: metastatic breast cancer; TACTIVE-U; Umbrella study; PROTAC
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms
• Other Study ID Numbers: C4891006; 2022-502228-34-00 (Registry Identifier: CTIS (EU))

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