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)

Breast Cancer Clinical Trial

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)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05573555
• Other study ID #: C4891023
• Secondary ID: 2022-502231-19-0
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: March 1, 2023
• Est. completion date: December 14, 2026

Study information

• Verified date: May 2024
• Source: Pfizer
• Contact: Pfizer CT.gov Call Center
• Phone: 1-800-718-1021
• Email: ClinicalTrials.gov_Inquiries[@]pfizer.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 47
• Est. completion date: December 14, 2026
• Est. primary completion date: December 14, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms

Intervention

Drug:
• ARV-471
Daily oral dosages of ARV-471 continuously, dose escalation/de-escalation in Phase 1b until RP2D determined, cycles lasting 28 days
• Ribociclib
Daily oral dosages of ribociclib consecutively for 21 days followed by 7 days off treatment, cycles lasting 28 days

Locations

Country	Name	City	State
Canada	CIUSSS- saguenay-Lac-Saint-Jean	Chicoutimi	Quebec
Canada	Jewish General Hospital	Montreal	Quebec
Canada	The Ottawa Hospital - General Campus	Ottawa	Ontario
Canada	Sunnybrook Research Institute	Toronto	Ontario
Canada	BC Cancer Vancouver	Vancouver	British Columbia
Canada	BC Cancer Vancouver	Vancouver	British Columbia
Italy	Azienda Ospedaliero Universitaria delle Marche	Ancona
Italy	Istituto di Candiolo IRCCS - Fondazione del Piemonte per l'Oncologia	Candiolo	Torino
Italy	Humanitas Istituto Clinico Catanese	Misterbianco	Catania
Italy	Fondazione IRCCS San Gerardo dei Tintori	Monza	Lombardia
Italy	Istituto Nazionale Tumori IRCCS Fondazione Pascale	Napoli	Campania
Italy	Istituto Oncologico Veneto IRCCS	Padova
Italy	Fondazione Policlinico Universitario Agostino Gemelli IRCCS - Università Cattolica del Sacro Cuore	Roma	Lazio
Spain	Hospital Universitari Dexeus	Barcelona	Catalunya [cataluña]
Spain	Hospital Universitari Vall d'Hebron	Barcelona	Barcelona [barcelona]
Spain	Hospital General Universitario Gregorio Marañon	Madrid	Madrid, Comunidad DE
Spain	Hospital Universitario 12 de Octubre	Madrid	Madrid, Comunidad DE
Spain	Hospital Universitario Virgen Del Rocio	Sevilla
United States	Brigham and Women's Hospital	Boston	Massachusetts
United States	Dana-Farber Cancer Institute	Boston	Massachusetts
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	Houston Area Locations The Woodland	Conroe	Texas
United States	Siteman Cancer Center - West County	Creve Coeur	Missouri
United States	Siteman Cancer Center - North County	Florissant	Missouri
United States	Houston Area Locations MDACC West Houston	Houston	Texas
United States	U.T. MD Anderson Cancer Center	Houston	Texas
United States	U.T. MD Anderson Cancer Center, Investigational Pharmacy Services - Unit 376	Houston	Texas
United States	University of Texas MD Anderson Cancer Center	Houston	Texas
United States	Houston Area Locations MDACC League City	League City	Texas
United States	Dana-Farber Cancer Institute - Chestnut Hill	Newton	Massachusetts
United States	Stanford Women's Cancer Center	Palo Alto	California
United States	Barnes Jewish Hospital Department of Laboratories	Saint Louis	Missouri
United States	Barnes Jewish Hospital Lab- South County	Saint Louis	Missouri
United States	Barnes-Jewish Hospital	Saint Louis	Missouri
United States	Siteman Cancer Center - South County	Saint Louis	Missouri
United States	Washington University School of Medicine	Saint Louis	Missouri
United States	Washington University School of Medicine - Siteman Cancer Center	Saint Louis	Missouri
United States	Siteman Cancer Center - St Peters	Saint Peters	Missouri
United States	UCSF Medical Center at Mission Bay	San Francisco	California
United States	Siteman Cancer Center - WUPI	Shiloh	Illinois
United States	Houston Area Locations MDACC Sugarland	Sugar Land	Texas
United States	Moffitt Cancer Center	Tampa	Florida
United States	Moffitt Cancer Center - International Plaza	Tampa	Florida
United States	Moffitt Cancer Center, Richard M. Shulze Family Foundation Outpatient Center	Tampa	Florida

Sponsors (2)

Lead Sponsor	Collaborator
Pfizer	Arvinas Estrogen Receptor, Inc.

Countries where clinical trial is conducted

United States,  Canada,  Italy,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)
Primary	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
Primary	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
Primary	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	Phase 1b, Drug Drug Interaction cohort and Phase 2: number of participants experiencing any AE, SAE, Treatment Related SAE	An adverse event (AE) were any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. An SAE is any untoward medical occurrence that, at any dose: resulted in death; required inpatient hospitalization or prolongation of existing hospitalization; was life-threatening; resulted in persistent or significant disability/ incapacity; congenital anomaly/birth defect and other important medical events. Treatment-related AE is any untoward medical occurrence attributed to study drug in a participant who received study drug. AEs were graded by the investigator according to the Common Terminology Criteria for Adverse Events (CTCAE version 5.0) and coded using MedDRA were reported. Grade 1=mild; Grade 2=moderate; Grade 3=severe and Grade 4=life-threatening or disabling and grade 5=death.	Up to 28 days after last dose of study treatment
Secondary	Phase 1b, Drug Drug Interaction cohort and Phase 2: number of participants with lab abnormalities - chemistry parameters	Blood samples were collected for analysis of clinical chemistry parameters. These included: alanine aminotransferase, alkaline phosphatase, aspartate aminotransferase, [international unit per liter (IU/L)] ; Lipase and amilase [IU/L] (limited to cycle1 only); Albumin, bilirubin, urea ,calcium, creatinine, glucose, magnesium, phosphate, uric acid chloride, potassium and sodium [millimol per liter (mmol/L)]; eGFR [milliliter per minute (ml/min)]. Number of participants with chemistry abnormalities by grade as per CTCAE version 5.0 were reported. Grade 1=mild; Grade 2=moderate; Grade 3=severe and Grade 4=life-threatening or disabling and grade 5=death. For laboratory tests without CTCAE grade definitions, results will be categorized as normal, abnormal, or not done.	Up to 28 days after last dose of study treatment
Secondary	Phase 1b, Drug Drug Interaction cohort and Phase 2: number of participants with lab abnormalities - Hematology and coagulation parameters	Blood samples were collected for the analysis of following hematology and coagulation parameters: hemoglobin [g/L], platelets, leukocytes, neutrophils, lymphocytes, monocytes, eosinophils and basophils [10^9/L]; partial thromboplastin time prolonged, international normalized ratio increased, prothrombin time. Number of participants with hematological and coagulation abnormalities by grade as per CTCAE version 5.0 were reported. Grade 1=mild; Grade 2=moderate; Grade 3=severe and Grade 4=life-threatening or disabling and grade 5=death. For laboratory tests without CTCAE grade definitions, results will be categorized as normal, abnormal, or not done.	Up to 28 days after last dose of study treatment
Secondary	Drug Drug Interaction cohort: number of participants with changes from baseline for ECG parameters	The following ECG parameters were analyzed and changes from baseline were assessed: heart rate, PR interval, QT interval, QRS interval and QT interval corrected using Fridericia's formula (QTcF).	Up to 28 days after last dose of study treatment
Secondary	Phase 1b: 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
Secondary	Phase 1b and Phase 2: Duration of Response by investigator assessment.	Duration of Response (DoR) is defined for participants with confirmed OR (CR or PR) as the time from the first documentation of OR to the first documentation of objective tumor progression or to death due to any cause, whichever occurs first.	Up to approximately 1 year
Secondary	Phase 1b and Phase2: Percentage of participants with Clinical Benefit Response by investigator assessment.	Clinical Benefit Response (CBR) is defined as the proportion of participants with Best Overall Response of confirmed CR or PR at any time, or Stable Disease (SD) =24 weeks	Up to approximately 1 year
Secondary	Phase 1b and Phase 2: Progression Free Survival by investigator assessment.	Progression Free Survival (PFS) is defined as the time from the date of first dose of study interventions to the date of first documentation of PD or death due to any cause, whichever occurs first.	Up to approximately 1 year
Secondary	Phase 1b: Maximum Observed Plasma Concentration (Cmax) of ARV-471 with and without co-administration of ribociclib	Concentration (Cmax) of ARV-471 with and without co-administration of ribociclib	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
Secondary	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	Exposure (AUCtau) of ARV-471 with and without co-administration of ribociclib	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
Secondary	Phase 1b and Phase 2: Maximum Observed Plasma Concentration (Cmax) of ARV-471	Plasma concentration of ARV-471	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
Secondary	Phase 1b and Phase 2: Maximum Observed Plasma Concentration (Cmax) of ARV-473	Plasma concentration of ARV-473	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
Secondary	Phase 1b and Phase 2: Phase 1b: Maximum Observed Plasma Concentration (Cmax) of ribociclib	Plasma concentration of ribociclib	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
Secondary	Phase 2: Overall Survival	Overall Survival (OS) is defined as the time from the date of first dose of study interventions to the date of death due to any cause	Through study completion, up to approximately 3 year
Secondary	Phase 2:ctDNA plasma quantitative changes from pre-treatment	To assess changes from baseline levels in plasma ctDNA with treatment and to evaluate potential predictability of their associations with clinical outcomes.	At predefined intervals throughout the treatment period, up to cycle 3 (each cycle is 28 days) and end of treatment

External Links

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