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)

Phase 2Active Not RecruitingNCT05548127

Pfizer37 enrolled

Overview

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.

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.

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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

Outcomes

Primary Outcomes

Phase 1b: number of participants with dose limiting toxicities

Dose Limiting Toxicities rate for ARV-471 in combination with abemaciclib, estimated based on data from DLT-evaluable participants during the DLT observation period (Cycle 1 \[28 days\]).

Time frame: 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.

Time frame: Up to approximately 1 year

Secondary Outcomes

Phase 1b 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.

Time frame: Up to 28 days after last dose of study treatment

Phase 1b 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.

Time frame: Up to 28 days after last dose of study treatment

Phase 1b 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 blood 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.

Time frame: Up to 28 days after last dose of study treatment

Phase 1b: percentage of participants with objective response by investigator assessment

Time frame: Up to approximately 1 year

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.

Time frame: Up to approximately 3 years

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

Time frame: Up to approximately 1 year

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.

Time frame: Up to approximately 3 years

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

Time frame: Through study completion, up to approximately 3 year

Phase 2:ctDNA plasma quantitative changes from pre-treatment

To assess changes from baseline levels in plasma circulating DNA (ctDNA) with treatment and to evaluate potential predictability of their associations with clinical outcome

Time frame: Day 1, 29 and 57 and End of Treatment (an average of 1 year)

Phase 1b: Area Under the Curve from Time Zero to end of dosing interval Evaluation of abemaciclib with or without ARV-471

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

Time frame: 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

Phase 1b: Maximum Observed Plasma Concentration (Cmax) of abemaciclib with or without ARV-471

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

Time frame: 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

Phase 1b and Phase 2: Maximum Observed Plasma Concentration (Cmax) of ARV-471

Plasma concentration of ARV-471

Time frame: 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

Phase 1b and Phase 2: Maximum Observed Plasma Concentration (Cmax) of abemaciclib

Plasma concentration of abemaciclib

Time frame: 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

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)

Overview

Conditions

Interventions

Eligibility

Locations (39)

Outcomes

Primary Outcomes

Secondary Outcomes