Clinical trial NCT05548127: 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)
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 A (ARV-471 in Combination With Abemaciclib)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_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: 2022-09-21
Enrollment: 37
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 abemaciclib. The decision to de-escalate the starting dose levels 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 \[first 28 days\]).

Phase 2 will further evaluate the preliminary antitumor activity and safety of the combination RP2D.
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 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.

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.

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 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

Primary outcomes:
measure: Phase 1b: number of participants with dose limiting toxicities
timeFrame: 28 days
measure: Phase 2: percentage of participants with objective response by investigator assessment
timeFrame: Up to approximately 1 year
Secondary outcomes:
measure: Phase 1b and Phase 2: number of participants experiencing any AE, SAE, Treatment Related SAE
timeFrame: Up to 28 days after last dose of study treatment
measure: Phase 1b 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: Phase 1b 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: 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 2: Overall Survival
timeFrame: Through study completion, up to approximately 3 year
measure: Phase 2:ctDNA plasma quantitative changes from pre-treatment
timeFrame: Day 1, 29 and 57 and End of Treatment (an average of 1 year)
measure: Phase 1b: Area Under the Curve from Time Zero to end of dosing interval Evaluation of abemaciclib with or without ARV-471
timeFrame: 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
measure: Phase 1b: Maximum Observed Plasma Concentration (Cmax) of abemaciclib with or without ARV-471
timeFrame: 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
measure: Phase 1b and Phase 2: Maximum Observed Plasma Concentration (Cmax) of ARV-471
timeFrame: 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
measure: Phase 1b and Phase 2: Maximum Observed Plasma Concentration (Cmax) of abemaciclib
timeFrame: 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
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 McKinley Hospital
state: Florida
city: Shiloh
country: United States
facility: Siteman Cancer Center - WUPI
state: Illinois
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
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: Siteman Cancer Center - South County
state: Missouri
city: Saint Peters
country: United States
facility: Siteman Cancer Center - St Peters
state: Missouri
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: Puyallup
country: United States
facility: Northwest Medical Specialties, PLLC
state: Washington
city: Tacoma
country: United States
facility: Northwest Medical Specialties, PLLC
state: Washington
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: Roma
country: Italy
facility: Fondazione Policlinico Universitario Agostino Gemelli IRCCS - Università Cattolica del Sacro Cuore
state: Lazio
city: Candiolo
country: Italy
facility: Istituto di Candiolo IRCCS - Fondazione del Piemonte per l'Oncologia
state: Torino
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: Clinica Universidad de Navarra
state: Madrid, Comunidad DE
city: Madrid
country: Spain
facility: Clínica Universidad de Navarra
state: Madrid, Comunidad DE
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
state: Madrid, Comunidad DE
city: Pamplona
country: Spain
facility: Clinica Universidad de Navarra
state: Navarra
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen Del Rocio
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References: