Clinical trial NCT06125522: 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 C)
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 AND OLDER WITH ER+ ADVANCED OR METASTATIC BREAST CANCER, SUB-STUDY C (ARV-471 IN COMBINATION WITH SAMURACICLIB)
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.
name: Carrick Therapeutics Limited
First posted: 2023-11-09
Enrollment: 11
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 samuraciclib. 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).

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 samuraciclib will be evaluated, at the doses selected as recommended dose for expansion (RDE(s)), in a DDI Assessment Cohort(s)
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to learn about the safety and effects of the study medicine called vepdegestrant. The safety and effects of vepdegestrant will be see when given with other medicines. 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.

This study is divided into separate sub-studies.

For Sub-Study C:

All the participants will receive vepdegestrant and a medicine called samuraciclib.

Vepdegestrant and samuraciclib will be taken once in a day 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 medicine is safe and effective.

Participant will continue to take vepdegestrant and samuraciclib 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: C4891024 is a prospective, open-label, multicenter, Phase 1b/2 sub-study to evaluate the safety, antitumor activity, and PK of ARV-471 with samuraciclib 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 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 breast cancer. At time of enrollment this must not be amendable 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).
* 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 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
* impaired cardiovascular function or clinically significant cardiovascular diseases
* concurrent administration of medications, food, or herb supplements that are strong inhibitors/inducers of CYP3A, strong CYP2D6 inhibitors 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: Drug Drug Interaction: To evaluate the effect of samuraciclib on PK of ARV 471.
timeFrame: From the start of Lead-in period (maximum 13 days) to the end of cycle 1 (at least 28 days)
measure: Drug Drug Interaction: To evaluate the effect of samuraciclib on PK of ARV 471.
timeFrame: From the start of Lead-in period (maximum 13 days) to the end of cycle 1 (at least 28 days)
measure: Phase 2: Percentage of Participants With Objective Response by investigator assessment
timeFrame: Up to approximately 1 year
measure: Drug Drug Interaction: • To evaluate the effect of ARV 471 on PK of samuraciclib.
timeFrame: From the start of Lead-in period (maximum 13 days) to the end of cycle 1 (at least 28 days))
measure: Drug Drug Interaction: • To evaluate the effect of ARV 471 on PK of samuraciclib.
timeFrame: From the start of Lead-in period (maximum 13 days) to the end of cycle 1 (at least 28 days))
Secondary outcomes:
measure: Phase 1b, Drug drug interaction and Phase 2: Evaluation of Safety and Tolerability of ARV-471 in combination with Samuraciclib
timeFrame: First study drug dose through a minimum of 28 Days After Last study drug administration
measure: Phase 1b: To evaluate antitumor activity of ARV-471 in combination with samuraciclib
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 and Phase 2: Plasma concentrations of ARV-471 and samuraciclib.
timeFrame: At predefined intervals throughout the treatment period, up to cycle 7 (each cycle is 28 days)
measure: Phase 1b: Evaluation of effect of samuraciclib on PK of ARV-471
timeFrame: At predefined intervals throughout the treatment period, up to cycle 7 (each cycle is 28 days)
measure: Phase 1b: Evaluation of effect of samuraciclib on PK of ARV-471
timeFrame: At predefined intervals throughout the treatment period, up to cycle 7 (each cycle is 28 days)
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
measure: Phase 2: To evaluate the correlation between TP53 mutation status and antitumor activity
timeFrame: Screening
measure: Phase 2: Overall Survival
timeFrame: Through study completion, up to approximately 3 year
Other outcomes:
Locations:
city: Fayetteville
country: United States
facility: Highlands Oncology Group
state: Arkansas
city: Rogers
country: United States
facility: Highlands Oncology Group
state: Arkansas
city: Springdale
country: United States
facility: Highlands Oncology Group
state: Arkansas
city: Palo Alto
country: United States
facility: Stanford Cancer Center
state: California
city: Palo Alto
country: United States
facility: Stanford Cancer Institute - Clinical Trials Office
state: California
city: Fort Collins
country: United States
facility: UCHealth Poudre Valley Hospital
state: Colorado
city: Fort Collins
country: United States
facility: UCHealth Harmony
state: Colorado
city: Greeley
country: United States
facility: UCHealth Greeley Hospital
state: Colorado
city: Loveland
country: United States
facility: UCHealth - Medical Center of the Rockies
state: Colorado
city: Shiloh
country: United States
facility: Memorial Hospital East
state: Illinois
city: Shiloh
country: United States
facility: Siteman Cancer Center - Shiloh
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
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: Anderlecht
country: Belgium
facility: Institut Jules Bordet
state: Bruxelles-capitale, Région DE
city: Dijon
country: France
facility: Centre Georges François Leclerc
state: Côte-d'or
city: Monza
country: Italy
facility: Fondazione IRCCS San Gerardo dei Tintori
state: Lombardia
city: Roma
country: Italy
facility: Fondazione Policlinico Universitario Agostino Gemelli IRCCS - Università Cattolica del Sacro Cuore
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References: