Clinical trial NCT05573555: 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 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 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 B (ARV-471 IN COMBINATION WITH RIBOCICLIB)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Breast Cancer
Keywords: TACTIVE-U; Umbrella study; PROTAC; metastatic breast cancer
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
Collaborators: name: Arvinas Estrogen Receptor, Inc.
First posted: 2022-10-10
Enrollment: 47
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 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).

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.

In addition, the potential drug-drug interaction (DDI) between ARV-471 and ribociclib will be evaluated, at the doses selected for the ph2 portion, in a DDI Assessment Cohort(s)
Primary purpose: TREATMENT

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.

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: at least 1 and no more than 2 lines of prior therapies for advanced/metastatic disease; 1, and only 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

Primary outcomes:
measure: Phase 1b: Number of Participants With Dose Limiting Toxicities
timeFrame: Cycle 1 (28 days)
measure: Phase 2: Percentage of Participants With Objective Response by investigator assessment
timeFrame: Up to approximately 1 year
measure: Drug Drug Interaction cohort: Area Under the Curve from Time Zero to end of dosing interval Evaluation of ribociclib with and without co-administration of ARV-471
timeFrame: pre-dose Day -1, 1, 8, 15, 29, 43, 57, 113, 169; 1, 2, 4, 6, 8 hours post dose on Day -1 and 15; post dose Day 8, 29 and 43
measure: Drug Drug Interaction cohort: Maximum Plasma Concentration (Cmax) of ribociclib with and without co-administration of ARV-471
timeFrame: pre-dose Day -1, 1, 8, 15, 29, 43, 57, 113, 169; 1, 2, 4, 6, 8 hours post dose on Day -1 and 15; post dose Day 8, 29 and 43
Secondary outcomes:
measure: Phase 1b, Drug Drug Interaction cohort and Phase 2: number of participants experiencing any AE, SAE, Treatment Related SAE
timeFrame: Up to 28 days after last dose of study treatment
measure: Phase 1b, Drug Drug Interaction cohort and Phase 2: number of participants with lab abnormalities - chemistry parameters
timeFrame: Up to 28 days after last dose of study treatment
measure: Phase 1b, Drug Drug Interaction cohort and Phase 2: number of participants with lab abnormalities - Hematology and coagulation parameters
timeFrame: Up to 28 days after last dose of study treatment
measure: Drug Drug Interaction cohort: number of participants with changes from baseline for ECG parameters
timeFrame: Up to 28 days after last dose of study treatment
measure: Phase 1b: Percentage of Participants With Objective Response by investigator assessment
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: Maximum Observed Plasma Concentration (Cmax) of ARV-471 with and without co-administration of ribociclib
timeFrame: Phase 1b: pre-dose Day -1, 1, 8, 15, 29, 43, 57, 113, 169; 1, 2, 4, 6, 8 hours post dose on Day -1 and 15; post dose Day 8, 29 and 43
measure: Phase 1b Area Under the Curve from Time Zero to end of dosing interval Evaluation of ARV-471 with and without co-administration of ribociclib
timeFrame: Phase 1b: pre-dose Day -1, 1, 8, 15, 29, 43, 57, 113, 169; 1, 2, 4, 6, 8 hours post dose on Day -1 and 15; post dose Day 8, 29 and 43
measure: Phase 1b and Phase 2: Maximum Observed Plasma Concentration (Cmax) of ARV-471
timeFrame: Phase 1b: pre-dose Day 8, 15, 29, 43, 57, 113, 169; 1, 2, 4, 6, 8 hours post dose on Day -1 and 15; post dose Day 8, 29 and 43 Phase 2: pre and post dose Day 8, 15, 29 and 43; pre - dose Day 57, 113 and 169
measure: Phase 1b and Phase 2: Maximum Observed Plasma Concentration (Cmax) of ARV-473
timeFrame: Phase 1b: pre-dose Day -1, 1, 8, 15, 29, 43, 57, 113, 169; 1, 2, 4, 6, 8 hours post dose on Day -1 and 15; post dose Day 8, 29 and 43 Phase 2: pre and post dose Day 8, 15, 29 and 43; pre - dose Day 57, 113 and 169
measure: Phase 1b and Phase 2: Phase 1b: Maximum Observed Plasma Concentration (Cmax) of ribociclib
timeFrame: Phase 1b: pre-dose Day -1, 1, 8, 15, 29, 43, 57, 113, 169; 1, 2, 4, 6, 8 hours post dose on Day 15; post dose Day 8, 29 and 43 Phase 2: pre and post dose Day 8, 15, 29 and 43; pre - dose Day 57, 113 and 169
measure: Phase 2: Overall Survival
timeFrame: Through study completion, up to approximately 3 year
measure: Phase 2:ctDNA plasma quantitative changes from pre-treatment
timeFrame: At predefined intervals throughout the treatment period, up to cycle 3 (each cycle is 28 days) and end of treatment
Other outcomes:
Locations:
city: Palo Alto
country: United States
facility: Stanford Women's Cancer Center
state: California
city: San Francisco
country: United States
facility: UCSF Medical Center at Mission Bay
state: California
city: Tampa
country: United States
facility: Moffitt Cancer Center - International Plaza
state: Florida
city: Tampa
country: United States
facility: Moffitt Cancer Center, Richard M. Shulze Family Foundation Outpatient Center
state: Florida
city: Tampa
country: United States
facility: Moffitt Cancer Center
state: Florida
city: Tampa
country: United States
facility: Moffitt McKinley Hospital
state: Florida
city: Shiloh
country: United States
facility: Siteman Cancer Center - WUPI
state: Illinois
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Brigham and Women's Hospital
state: Massachusetts
city: Boston
country: United States
facility: Dana-Farber Cancer Institute
state: Massachusetts
city: Newton
country: United States
facility: Dana-Farber Cancer Institute - Chestnut Hill
state: Massachusetts
city: Creve Coeur
country: United States
facility: Siteman Cancer Center - West County
state: Missouri
city: Florissant
country: United States
facility: Siteman Cancer Center - North County
state: Missouri
city: Saint Louis
country: United States
facility: Barnes Jewish Hospital Department of Laboratories
state: Missouri
city: Saint Louis
country: United States
facility: Barnes-Jewish Hospital
state: Missouri
city: Saint Louis
country: United States
facility: Washington University School of Medicine - Siteman Cancer Center
state: Missouri
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Saint Louis
country: United States
facility: Barnes Jewish Hospital Lab- South County
state: Missouri
city: Saint Louis
country: United States
facility: Siteman Cancer Center - South County
state: Missouri
city: Saint Peters
country: United States
facility: Siteman Cancer Center - St Peters
state: Missouri
city: Conroe
country: United States
facility: Houston Area Locations The Woodland
state: Texas
city: Houston
country: United States
facility: U.T. MD Anderson Cancer Center, Investigational Pharmacy Services - Unit 376
state: Texas
city: Houston
country: United States
facility: U.T. MD Anderson Cancer Center
state: Texas
city: Houston
country: United States
facility: University of Texas MD Anderson Cancer Center
state: Texas
city: Houston
country: United States
facility: Houston Area Locations MDACC West Houston
state: Texas
city: League City
country: United States
facility: Houston Area Locations MDACC League City
state: Texas
city: Sugar Land
country: United States
facility: Houston Area Locations MDACC Sugarland
state: Texas
city: Vancouver
country: Canada
facility: BC Cancer Vancouver
state: British Columbia
city: Vancouver
country: Canada
facility: BC Cancer Vancouver
state: British Columbia
city: Ottawa
country: Canada
facility: The Ottawa Hospital - General Campus
state: Ontario
city: Toronto
country: Canada
facility: Sunnybrook Research Institute
state: Ontario
city: Chicoutimi
country: Canada
facility: CIUSSS- saguenay-Lac-Saint-Jean
state: Quebec
city: Montreal
country: Canada
facility: Jewish General Hospital
state: Quebec
city: Napoli
country: Italy
facility: Istituto Nazionale Tumori IRCCS Fondazione Pascale
state: Campania
city: Misterbianco
country: Italy
facility: Humanitas Istituto Clinico Catanese
state: Catania
city: Roma
country: Italy
facility: Fondazione Policlinico Universitario Agostino Gemelli IRCCS - Università Cattolica del Sacro Cuore
state: Lazio
city: Monza
country: Italy
facility: Fondazione IRCCS San Gerardo dei Tintori
state: Lombardia
city: Candiolo
country: Italy
facility: Istituto di Candiolo IRCCS - Fondazione del Piemonte per l'Oncologia
state: Torino
city: Ancona
country: Italy
facility: Azienda Ospedaliero Universitaria delle Marche
city: Padova
country: Italy
facility: Istituto Oncologico Veneto IRCCS
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebron
state: Barcelona [barcelona]
city: Barcelona
country: Spain
facility: Hospital Universitari Dexeus
state: Catalunya [cataluña]
city: Madrid
country: Spain
facility: Hospital General Universitario Gregorio Marañon
state: Madrid, Comunidad DE
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: