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)

NCT05573555 | Active Not Recruiting Phase 1 DMC FDA Drug

• 2 other identifiers: C48910232022-502231-19-00
• Study Type: interventional
• Target: 20
• Locations: 4 countries
• Sites: 29

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.

Conditions

Breast Cancer

Keywords

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

Outcome Measures

Primary Outcomes (4)

• 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 \[28 days\]).

  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.

  Up to approximately 1 year

• 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

  Exposure (AUCtau) of ribociclib with and without co-administration of ARV-471

  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

• Drug Drug Interaction cohort: Maximum Plasma Concentration (Cmax) of ribociclib with and without co-administration of ARV-471

  Concentration (Cmax) of ribociclib with and without co-administration of ARV-471

  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 (15)

• Phase 1b, Drug Drug Interaction cohort and Phase 2: number of participants experiencing any AE, SAE, Treatment Related SAE

  Up to 28 days after last dose of study treatment

• Phase 1b, Drug Drug Interaction cohort and Phase 2: number of participants with lab abnormalities - chemistry parameters

  Up to 28 days after last dose of study treatment

• Phase 1b, Drug Drug Interaction cohort and Phase 2: number of participants with lab abnormalities - Hematology and coagulation parameters

  Up to 28 days after last dose of study treatment

• Drug Drug Interaction cohort: number of participants with changes from baseline for ECG parameters

  Up to 28 days after last dose of study treatment

• Phase 1b: Percentage of Participants With Objective Response by investigator assessment

  Up to approximately 1 year

Study Arms (1)

ARV-471 in combination with Ribociclib

EXPERIMENTAL

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

Drug: ARV-471; Drug: Ribociclib

Interventions

ARV-471 DRUG

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

ARV-471 in combination with Ribociclib

Ribociclib DRUG

Daily oral dosages of ribociclib consecutively for 21 days followed by 7 days off treatment, cycles lasting 28 days

ARV-471 in combination with Ribociclib

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 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.

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 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

Sponsors & Collaborators

• Pfizer: lead
• Arvinas Estrogen Receptor, Inc.: collaborator

Study Sites (29)

Stanford Women's Cancer Center

Palo Alto, California, 94304, United States

Location

UCSF Medical Center at Mission Bay

San Francisco, California, 94158, United States

Location

Moffitt Cancer Center - International Plaza

Tampa, Florida, 33607, United States

Location

Moffitt Cancer Center, Richard M. Shulze Family Foundation Outpatient Center

Tampa, Florida, 33612, United States

Location

Moffitt Cancer Center

Tampa, Florida, 33612, United States

Location

Moffitt McKinley Hospital

Tampa, Florida, 33612, United States

Location

Siteman Cancer Center - WUPI

Shiloh, Illinois, 62269, United States

Location

Brigham and Women's Hospital

Boston, Massachusetts, 02115, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Dana-Farber Cancer Institute - Chestnut Hill

Newton, Massachusetts, 02459, 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

Siteman Cancer Center

St Louis, Missouri, 63108, United States

Location

Barnes Jewish Hospital Department of Laboratories

St Louis, Missouri, 63110, 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

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Barnes Jewish Hospital Lab- South County

St Louis, Missouri, 63129, United States

Location

Siteman Cancer Center - South County

St Louis, Missouri, 63129, United States

Location

BC Cancer Vancouver

Vancouver, British Columbia, V5Z 1H7, Canada

Location

BC Cancer Vancouver

Vancouver, British Columbia, V5Z 4E6, Canada

Location

The Ottawa Hospital - General Campus

Ottawa, Ontario, K1H 8L6, Canada

Location

Sunnybrook Research Institute

Toronto, Ontario, M4N 3M5, Canada

Location

CIUSSS- saguenay-Lac-Saint-Jean

Chicoutimi, Quebec, G7H 5H6, Canada

Location

Jewish General Hospital

Montreal, Quebec, H3T 1E2, Canada

Location

Fondazione IRCCS San Gerardo dei Tintori

Monza, Lombardy, 20900, Italy

Location

Hospital Universitario 12 de Octubre

Madrid, Madrid, Comunidad de, 28041, Spain

Location

Hospital Universitario Virgen Del Rocio

Seville, 41013, Spain

Location

Related Links

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

MeSH Terms

Conditions

Breast Neoplasms

Interventions

ribociclib

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 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)

Study Record Dates

• First Submitted: October 5, 2022
• First Posted: October 10, 2022
• Study Start: March 1, 2023
• Primary Completion (Estimated): December 30, 2026
• Study Completion (Estimated): December 30, 2026
• Last Updated: March 9, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share

Locations

CA (6); IT (1); US (20); ES (2)