Back to resultsTACTIVE-U: A Study to Learn About the Study Medicine (Called ARV-471) When Given With Other Medicines in People With Advanced or Metastatic Breast Cancer (Sub-Study B)
Primary Purpose
Breast Cancer
Status
Recruiting
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
ARV-471
Ribociclib
Sponsored by
About this trial
This is an interventional treatment trial for Breast Cancer focused on measuring TACTIVE-U; Umbrella study; PROTAC; metastatic breast cancer
Eligibility Criteria
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: up to 2 lines of prior therapies for advanced/metastatic disease; 1 line of any CDK4/6 inhibitor-based regimen is required (in any setting eg adjuvant, 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 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
- 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
Sites / Locations
- Siteman Cancer Center - WUPIRecruiting
- Siteman Cancer Center - West CountyRecruiting
- Siteman Cancer Center - North CountyRecruiting
- Barnes Jewish Hospital Department of LaboratoriesRecruiting
- Barnes-Jewish HospitalRecruiting
- Washington University School of Medicine - Siteman Cancer CenterRecruiting
- Washington University School of MedicineRecruiting
- Washington University
- Barnes Jewish Hospital Lab- South CountyRecruiting
- Siteman Cancer Center - South CountyRecruiting
- Siteman Cancer Center - St PetersRecruiting
- The Ottawa Hospital - General CampusRecruiting
- Sunnybrook Research InstituteRecruiting
- CIUSSS- saguenay-Lac-Saint-JeanRecruiting
- Jewish General HospitalRecruiting
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
ARV-471 in combination with Ribociclib
Arm Description
ARV-471 administered orally QD continuously and Ribociclib administered orally QD consecutively for 21 days followed by 7 days off treatment on 28-day cycles
Outcomes
Primary Outcome Measures
Phase 1b: Number of Participants With Dose Limiting Toxicities
Dose Limiting Toxicities rate for ARV-471 in combination with Ribociclib, 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.
Secondary Outcome Measures
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.
Phase 1b: Evaluation of effect of ribociclib on PK of ARV-471
AUCtau and Cmax of ARV-471 with and without co-administration of ribociclib
Phase 1b and Phase 2: Evaluation of Safety and Tolerability of ARV-471 in combination with Ribociclib
AEs as characterized by type, frequency, intensity as graded by NCI CTCAE version 5.0, timing, seriousness, and relationship to ARV-471 in combination with ribociclib.
Laboratory test abnormalities as characterized by type, frequency, intensity (as graded by NCI CTCAE version 5.0), and timing.
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.
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
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.
Phase 1b and Phase 2: Plasma concentrations of ARV-471 and ribociclib.
To evaluate the plasma exposure of ARV-471 and ribociclib when ARV-471 and ribociclib are given in combination.
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
Phase 2:ctDNA plasma quantitative changes from pre-treatment
To assess changes from baseline levels in plasma ctDNA with treatment and to evaluate potential predictability of their associations with clinical outcomes.
Full Information
NCT ID
NCT05573555
First Posted
October 5, 2022
Last Updated
July 17, 2023
Sponsor
Pfizer
Collaborators
Arvinas Estrogen Receptor, Inc.
1. Study Identification
Unique Protocol Identification Number
NCT05573555
Brief Title
TACTIVE-U: A Study to Learn About the Study Medicine (Called ARV-471) When Given With Other Medicines in People With Advanced or Metastatic Breast Cancer (Sub-Study B)
Official Title
TACTIVE-U: AN INTERVENTIONAL SAFETY AND EFFICACY PHASE 1B/2, OPEN-LABEL UMBRELLA STUDY TO INVESTIGATE TOLERABILITY, PK, AND ANTITUMOR ACTIVITY OF 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 B (ARV-471 IN COMBINATION WITH RIBOCICLIB)
Study Type
Interventional
2. Study Status
Record Verification Date
July 2023
Overall Recruitment Status
Recruiting
Study Start Date
March 1, 2023 (Actual)
Primary Completion Date
April 6, 2026 (Anticipated)
Study Completion Date
October 6, 2027 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Pfizer
Collaborators
Arvinas Estrogen Receptor, Inc.
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
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 B:
All participants will receive ARV-471 and a medicine called ribociclib. ARV-471 and ribociclib will be given at the same time by mouth, at home, 1 time a day.
The experiences of people receiving the study medicine will be examined. This will help determine if the study medicine is safe and effective.
Participants will continue to take ARV-471 and ribociclib 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
C4891023 is a prospective, open-label, multicenter, Phase 1b/2 sub-study to evaluate the safety, antitumor activity, and PK of ARV-471 with ribociclib in the treatment of participants with A/MBC. The sub-study is part of Umbrella platform, TACTIVE-U, comprising multiple sub-studies that independently evaluate ARV-471 in participants with with Estrogen Receptor Positive/Human Epidermal Growth Factor Receptor 2 Negative (ER+/HER2-) Advanced or Metastatic Breast Cancer. ARV-471 will act as the backbone therapy given in combination with other anticancer agents thought to have clinical relevance in ER+ breast cancer.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Breast Cancer
Keywords
TACTIVE-U; Umbrella study; PROTAC; metastatic breast cancer
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Sequential Assignment
Model Description
Phase 1b will use an escalation/de-escalation approach to determine the RP2D of ARV-471 when administered in combination with ribociclib. The decision to escalate the starting dose level of ARV-471 will be using mTPI-2 decision criteria based on the number of DLT-evaluable participants and the number of DLTs in those participants during the DLT observation period (Cycle 1 [first 28 days]).
During Phase 1b, a 7 days lead-in period will be conducted with ARV-471 as monotherapy.
Phase 2 will further evaluate the preliminary antitumor activity and safety of the combination RP2D.
Masking
None (Open Label)
Allocation
N/A
Enrollment
35 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
ARV-471 in combination with Ribociclib
Arm Type
Experimental
Arm Description
ARV-471 administered orally QD continuously and Ribociclib administered orally QD consecutively for 21 days followed by 7 days off treatment on 28-day cycles
Intervention Type
Drug
Intervention Name(s)
ARV-471
Intervention Description
Daily oral dosages of ARV-471 continuously, dose escalation/de-escalation in Phase 1b until RP2D determined, cycles lasting 28 days
Intervention Type
Drug
Intervention Name(s)
Ribociclib
Intervention Description
Daily oral dosages of ribociclib consecutively for 21 days followed by 7 days off treatment, cycles lasting 28 days
Primary Outcome Measure Information:
Title
Phase 1b: Number of Participants With Dose Limiting Toxicities
Description
Dose Limiting Toxicities rate for ARV-471 in combination with Ribociclib, estimated based on data from DLT-evaluable participants during the DLT observation period (Cycle 1 [28 days]).
Time Frame
28 days
Title
Phase 2: Percentage of Participants With Objective Response by investigator assessment
Description
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.
Time Frame
Up to approximately 1 year
Secondary Outcome Measure Information:
Title
Phase 1b: Percentage of Participants With Objective Response by investigator assessment
Description
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.
Time Frame
Up to approximately 1 year
Title
Phase 1b: Evaluation of effect of ribociclib on PK of ARV-471
Description
AUCtau and Cmax of ARV-471 with and without co-administration of ribociclib
Time Frame
At predefined intervals throughout the treatment period, up to cycle 7 (each cycle is 28 days)
Title
Phase 1b and Phase 2: Evaluation of Safety and Tolerability of ARV-471 in combination with Ribociclib
Description
AEs as characterized by type, frequency, intensity as graded by NCI CTCAE version 5.0, timing, seriousness, and relationship to ARV-471 in combination with ribociclib.
Laboratory test abnormalities as characterized by type, frequency, intensity (as graded by NCI CTCAE version 5.0), and timing.
Time Frame
First study drug dose through a minimum of 28 Days After Last study drug administration
Title
Phase 1b and Phase 2: Duration of Response by investigator assessment.
Description
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.
Time Frame
Up to approximately 1 year
Title
Phase 1b and Phase2: Percentage of participants with Clinical Benefit Response by investigator assessment.
Description
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
Time Frame
Up to approximately 1 year
Title
Phase 1b and Phase 2: Progression Free Survival by investigator assessment.
Description
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.
Time Frame
Up to approximately 1 year
Title
Phase 1b and Phase 2: Plasma concentrations of ARV-471 and ribociclib.
Description
To evaluate the plasma exposure of ARV-471 and ribociclib when ARV-471 and ribociclib are given in combination.
Time Frame
At predefined intervals throughout the treatment period, up to cycle 7 (each cycle is 28 days)
Title
Phase 2: Overall Survival
Description
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
Time Frame
Through study completion, up to approximately 3 year
Title
Phase 2:ctDNA plasma quantitative changes from pre-treatment
Description
To assess changes from baseline levels in plasma ctDNA with treatment and to evaluate potential predictability of their associations with clinical outcomes.
Time Frame
At predefined intervals throughout the treatment period, up to cycle 3 (each cycle is 28 days) and end of treatment
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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: up to 2 lines of prior therapies for advanced/metastatic disease; 1 line of any CDK4/6 inhibitor-based regimen is required (in any setting eg adjuvant, 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 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
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Pfizer CT.gov Call Center
Phone
1-800-718-1021
Email
ClinicalTrials.gov_Inquiries@pfizer.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Pfizer CT.gov Call Center
Organizational Affiliation
Pfizer
Official's Role
Study Director
Facility Information:
Facility Name
Siteman Cancer Center - WUPI
City
Shiloh
State/Province
Illinois
ZIP/Postal Code
62269
Country
United States
Individual Site Status
Recruiting
Facility Name
Siteman Cancer Center - West County
City
Creve Coeur
State/Province
Missouri
ZIP/Postal Code
63141
Country
United States
Individual Site Status
Recruiting
Facility Name
Siteman Cancer Center - North County
City
Florissant
State/Province
Missouri
ZIP/Postal Code
63031
Country
United States
Individual Site Status
Recruiting
Facility Name
Barnes Jewish Hospital Department of Laboratories
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Individual Site Status
Recruiting
Facility Name
Barnes-Jewish Hospital
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Individual Site Status
Recruiting
Facility Name
Washington University School of Medicine - Siteman Cancer Center
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Individual Site Status
Recruiting
Facility Name
Washington University School of Medicine
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Individual Site Status
Recruiting
Facility Name
Washington University
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Individual Site Status
Not yet recruiting
Facility Name
Barnes Jewish Hospital Lab- South County
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63129
Country
United States
Individual Site Status
Recruiting
Facility Name
Siteman Cancer Center - South County
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63129
Country
United States
Individual Site Status
Recruiting
Facility Name
Siteman Cancer Center - St Peters
City
Saint Peters
State/Province
Missouri
ZIP/Postal Code
63376
Country
United States
Individual Site Status
Recruiting
Facility Name
The Ottawa Hospital - General Campus
City
Ottawa
State/Province
Ontario
ZIP/Postal Code
K1H 8L6
Country
Canada
Individual Site Status
Recruiting
Facility Name
Sunnybrook Research Institute
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M4N 3M5
Country
Canada
Individual Site Status
Recruiting
Facility Name
CIUSSS- saguenay-Lac-Saint-Jean
City
Chicoutimi
State/Province
Quebec
ZIP/Postal Code
G7H 5H6
Country
Canada
Individual Site Status
Recruiting
Facility Name
Jewish General Hospital
City
Montreal
State/Province
Quebec
ZIP/Postal Code
H3T 1E2
Country
Canada
Individual Site Status
Recruiting
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing 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.
IPD Sharing URL
https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests
Links:
URL
https://pmiform.com/clinical-trial-info-request?StudyID=C4891023
Description
To obtain contact information for a study center near you, click here.
Learn more about this trial
TACTIVE-U: A Study to Learn About the Study Medicine (Called ARV-471) When Given With Other Medicines in People With Advanced or Metastatic Breast Cancer (Sub-Study B)
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