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Pfizer Oncology
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The safety and efficacy of this agent(s), or use in this setting, has not been established or is subject to confirmation. For an agent(s) whose safety and efficacy has not been established or confirmed, future regulatory approval or commercial availability is not guaranteed.

Clinical Trial Details

Geo Regions

Category

Breast Cancer

Vepdegestrant (ARV-471)*

Vepdegestrant is an investigational compound. Its safety and efficacy have not been established. * Vepdegestrant is being co-developed with Arvinas.

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)

Phase 1 /2

NCT05573555

Active enrolling

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Locations

United States, Canada, Italy, Spain

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Study design
Participant Group/Arm

EXPERIMENTAL: ARV-471 in combination with Ribociclib

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

Intervention/Treatment

DRUG: ARV-471

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

DRUG: Ribociclib

Daily oral dosages of ribociclib consecutively for 21 days followed by 7 days off treatment, cycles lasting 28 days
Study design table for Clinical Trial
Key eligibility criteria
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
Key dates
Study start date
  • March 2023
Estimated Study Completion Date
  • January 2027
Key endpoints
Primary Outcome Measures
Outcome Measure

Phase 1b: Number of Participants With Dose Limiting Toxicities

Measure Description

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 \[28 days\]).

Time Frame

Cycle 1 (28 days)

Outcome Measure

Phase 2: Percentage of Participants With Objective Response by investigator assessment

Measure Description

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

Outcome Measure

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

Measure Description

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

Time Frame

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

Outcome Measure

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

Measure Description

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

Time Frame

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 Outcome Measures table for Clinical Trial
Secondary Outcome Measures:
Outcome Measure

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

Measure Description

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

Outcome Measure

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

Measure Description

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.

Time Frame

Up to 28 days after last dose of study treatment

Outcome Measure

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

Measure Description

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

Outcome Measure

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

Measure Description

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).

Time Frame

Up to 28 days after last dose of study treatment

Outcome Measure

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

Measure Description

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

Outcome Measure

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

Measure Description

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 1 year

Outcome Measure

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

Measure Description

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

Outcome Measure

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

Measure Description

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 1 year

Outcome Measure

Phase 1b: Maximum Observed Plasma Concentration (Cmax) of ARV-471 with and without co-administration of ribociclib

Measure Description

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

Time Frame

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

Outcome Measure

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

Measure Description

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

Time Frame

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

Outcome Measure

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

Measure Description

Plasma concentration of ARV-471

Time Frame

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

Outcome Measure

Phase 1b and Phase 2: Maximum Observed Plasma Concentration (Cmax) of ARV-473

Measure Description

Plasma concentration of ARV-473

Time Frame

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

Outcome Measure

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

Measure Description

Plasma concentration of ribociclib

Time Frame

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

Outcome Measure

Phase 2: Overall Survival

Measure Description

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

Outcome Measure

Phase 2:ctDNA plasma quantitative changes from pre-treatment

Measure Description

To assess changes from baseline levels in plasma ctDNA with treatment and to evaluate potential predictability of their associations with clinical outcomes.

Time Frame

At predefined intervals throughout the treatment period, up to cycle 3 (each cycle is 28 days) and end of treatment

Secondary Outcome Measures table for Clinical Trial
Number of participants

47

Collaborators and investigators

Sponsor: Pfizer

Collaborator: Arvinas Estrogen Receptor, Inc.

This information is current as of October 8th 2024.

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More Information Close NCT# stands for National Clinical Trial number. This is a unique identification code given to each clinical trial registered on ClinicalTrials.gov. The format is "NCT" followed by an 8-digit number (for example, NCT00000419). Also called the ClinicalTrials.gov identifier. NCT05573555