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)

NCT06125522 | Active Not Recruiting Phase 1 DMC FDA Drug

• 2 other identifiers: C48910242023-507125-41-00
• Study Type: interventional
• Target: 11
• Locations: 4 countries
• Sites: 21

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.

Conditions

Breast Cancer

Keywords

TACTIVE-U; Umbrella study; PROTAC; metastatic breast cancer

Outcome Measures

Primary Outcomes (6)

• Phase 1b: Number of Participants With Dose Limiting Toxicities

  Dose Limiting Toxicities rate for ARV-471 in combination with Samuraciclib, estimated based on data from DLT-evaluable participants during the DLT observation period (Cycle 1).

  28 days

• Drug Drug Interaction: To evaluate the effect of samuraciclib on PK of ARV 471.

  Steady-state Area under the plasma concentration versus time curve (AUCtau) of ARV-471 with and without coadministration of samuraciclib

  From the start of Lead-in period (maximum 13 days) to the end of cycle 1 (at least 28 days)

• Drug Drug Interaction: To evaluate the effect of samuraciclib on PK of ARV 471.

  Steady-state Peak Plasma concentration ( Cmax) of ARV-471 with and without coadministration of samuraciclib

  From the start of Lead-in period (maximum 13 days) to the end of cycle 1 (at least 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

• Drug Drug Interaction: • To evaluate the effect of ARV 471 on PK of samuraciclib.

  Single dose AUC0-72 of samuraciclib with and without coadministration of ARV 471.

  From the start of Lead-in period (maximum 13 days) to the end of cycle 1 (at least 28 days))

• Drug Drug Interaction: • To evaluate the effect of ARV 471 on PK of samuraciclib.

  Single dose Cmax of samuraciclib with and without coadministration of ARV 471.

  From the start of Lead-in period (maximum 13 days) to the end of cycle 1 (at least 28 days))

Secondary Outcomes (11)

• Phase 1b, Drug drug interaction and Phase 2: Evaluation of Safety and Tolerability of ARV-471 in combination with Samuraciclib

  First study drug dose through a minimum of 28 Days After Last study drug administration

• Phase 1b: To evaluate antitumor activity of ARV-471 in combination with samuraciclib

  Up to approximately 1 year

• Phase 1b and Phase 2: Duration of Response by investigator assessment.

  Up to approximately 1 year

• Phase 1b and Phase2: Percentage of participants with Clinical Benefit Response by investigator assessment.

  Up to approximately 1 year

• Phase 1b and Phase 2: Progression Free Survival by investigator assessment.

  Up to approximately 1 year

Study Arms (1)

ARV-471 in combination with Samuraciclib

EXPERIMENTAL

ARV-471 administered orally QD continuously and Samuraciclib administered orally QD continuously on 28-day cycles

Drug: vepdegestrant; Drug: Samuraciclib

Interventions

Samuraciclib DRUG

Daily oral dosages of Samuraciclib continuously, dose escalation/de-escalation in Phase 1b until RP2D determined, cycles lasting 28 days

ARV-471 in combination with Samuraciclib

vepdegestrant DRUG

Daily oral dosages of ARV-471 continuously, dose escalation/de-escalation in Phase 1b until RP2D determined, cycles lasting 28 days

Also known as: ARV-471 / PF-07850327

ARV-471 in combination with Samuraciclib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Carrick Therapeutics Limited: collaborator
• Pfizer: lead
• Arvinas Estrogen Receptor, Inc.: collaborator

Study Sites (21)

Highlands Oncology Group

Fayetteville, Arkansas, 72703, United States

Location

Highlands Oncology Group

Rogers, Arkansas, 72758, United States

Location

Highlands Oncology Group

Springdale, Arkansas, 72762, United States

Location

Clinical and Translational Research Unit (CTRU)

Palo Alto, California, 94304, United States

Location

Stanford Women's Cancer Center

Palo Alto, California, 94304, United States

Location

UCHealth Poudre Valley Hospital

Fort Collins, Colorado, 80524, United States

Location

UCHealth Harmony

Fort Collins, Colorado, 80528, United States

Location

UCHealth Greeley Hospital

Greeley, Colorado, 80634, United States

Location

UCHealth - Medical Center of the Rockies

Loveland, Colorado, 80538, United States

Location

Memorial Hospital East

Shiloh, Illinois, 62269, United States

Location

Siteman Cancer Center - Shiloh

Shiloh, Illinois, 62269, United States

Location

Siteman Cancer Center - St Peters

City of Saint Peters, Missouri, 63376, United States

Location

Siteman Cancer Center - West County

Creve Coeur, Missouri, 63141, United States

Location

Siteman Cancer Center - North County

Florissant, Missouri, 63031, United States

Location

Barnes-Jewish Hospital

St Louis, Missouri, 63110, United States

Location

Washington University School of Medicine - Siteman Cancer Center

St Louis, Missouri, 63110, United States

Location

Siteman Cancer Center - South County

St Louis, Missouri, 63129, United States

Location

Institut Jules Bordet

Anderlecht, Bruxelles-capitale, Région de, 1070, Belgium

Location

Centre Georges François Leclerc

Dijon, Côte-d'or, 21079, France

Location

Fondazione IRCCS San Gerardo dei Tintori

Monza, Lombardy, 20900, Italy

Location

Fondazione Policlinico Universitario Agostino Gemelli IRCCS - Università Cattolica del Sacro Cuore

Roma, 00168, Italy

Location

Related Links

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

MeSH Terms

Conditions

Breast Neoplasms

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Study Officials

• Pfizer CT.gov Call Center

  Pfizer

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 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)

Study Record Dates

• First Submitted: October 16, 2023
• First Posted: November 9, 2023
• Study Start: January 10, 2024
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2026
• Last Updated: May 6, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will share

Locations

US (17); FR (1); IT (2); BE (1)