Tka Assay for CDK4/6i

Use of DiviTum-TKa as a Biomarker Assay for CDK4/6 Inhibitor Medication Compliance and Drug-Drug Interaction Assessment in ER/PR Positive Metastatic Breast Cancer

This clinical trial assesses whether using a test developed by DiviTum can identify optimal levels of CDK 4/6 inhibitor medications in the blood and whether assessing medical compliance and drug-drug interactions can optimize (improve) these levels in patients with estrogen receptor (ER) or progesterone receptor (PR) positive, and human epidermal growth factor receptor 2 (HER2)-negative breast cancer that has spread from where it first started (primary site) to other places in the body (metastatic) and are receiving CDK 4/6 inhibitors. CDK4/6 inhibitors in combination with endocrine therapy (ET) is first line treatment for metastatic hormone positive (ER/PR positive) breast cancer (mBC). Thymidine kinase is a biomarker (biological molecule found in blood, other body fluids, or tissues that is a sign of a condition or disease) that reflects cell proliferation (an increase in the number of cells as a result of cell growth and cell division). DiviTum-thymidine kinase activity (TKa) is a Food and Drug Administration approved assay which showed that a TKa is associated with the decreased likelihood of disease progression within 30 days or 60 days post testing. Using the DiviTum-TKa may improve medication compliance and remove potential drug-drug interactions in patients with ER/PR positive HER2-negative MBC.

Study Overview

• Status: Completed
• Conditions: Anatomic Stage IV Breast Cancer AJCC v8; Metastatic HER2-Negative Breast Carcinoma
• Intervention / Treatment: Device: DiviTum-TKa

Detailed Description

PRIMARY OBJECTIVE:

I. To estimate the rate of improvement in CDK4/6 inhibitor response (i.e. moving from profile 3 to profiles 1 or 2) in cycles 2 and 3 after counseling for medication compliance and adjustment of potential deleterious drug-drug interactions.

SECONDARY OBJECTIVES:

I. Estimate the rate of sub-optimal CDK 4/6 inhibitor response (profile 3) in patients with metastatic hormone positive breast cancer in cycle 1 of CDK4/6 inhibitor and endocrine therapy in the first line setting.

II. Compare clinical benefit rate (CBR) in patients with sub-optimal (profile 3) and optimal (profiles 1 and 2) CDK4/6 inhibitor response after both cycles 1 and cycle 3.

III. Compare progression free survival (PFS) rates at 6 months (mo), 12 mo, 18 mo in patients with sub-optimal (profile 3) and optimal (profiles 1 and 2) CDK 4/6 inhibitor response after both cycles 1 and cycle 3.

IV. Assess CDK4/6 inhibitor response via TKa levels upon CDK4/6 inhibitor dose reductions or changes in CDK4/6 inhibitor regimens.

V. Compare CDK4/6 inhibitor response profiles across the three CDK 4/6 inhibitors among different patients and within the same patients if CDK4/6 inhibitor is changed throughout treatment course.

VI. Correlate TKa levels with tumor marker levels. VII. Assess plasma concentrations of CDK4/6 inhibitor drugs in patients with suboptimal TKa levels.

OUTLINE:

Patients undergo collection of blood samples per standard of care (SOC) on days 1, 15, and 28 of cycle 1, days 15 and 28 of cycle 2, days 15 and 28 of cycle 3, and day 28 of subsequent cycles for up to 12 cycles for analysis by DiviTum-TKa in the absence of disease progression or unacceptable toxicity.

After completion of study intervention, patients are followed up for 2 years.

• Study Type: Interventional
• Enrollment (Actual): 34
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Connecticut
    • Derby, Connecticut, United States, 06418
      • Smilow Cancer Hospital-Derby Care Center
    • Fairfield, Connecticut, United States, 06824
      • Smilow Cancer Hospital Care Center-Fairfield
    • Glastonbury, Connecticut, United States, 06033
      • Smilow Cancer Hospital Care Center at Glastonbury
    • Greenwich, Connecticut, United States, 06830
      • Smilow Cancer Hospital Care Center at Greenwich
    • Guilford, Connecticut, United States, 06437
      • Smilow Cancer Hospital Care Center - Guilford
    • Hamden, Connecticut, United States, 06518
      • Smilow Cancer Hospital-Hamden Care Center
    • Hartford, Connecticut, United States, 06105
      • Smilow Cancer Hospital Care Center at Saint Francis
    • New Haven, Connecticut, United States, 06520
      • Yale University
    • New Haven, Connecticut, United States, 06510
      • Smilow Cancer Center/Yale-New Haven Hospital
    • New Haven, Connecticut, United States, 06511
      • Yale-New Haven Hospital Saint Raphael Campus
    • North Haven, Connecticut, United States, 06473
      • Yale-New Haven Hospital North Haven Medical Center
    • Orange, Connecticut, United States, 06477
      • Smilow Cancer Hospital-Orange Care Center
    • Stamford, Connecticut, United States, 06902
      • Smilow Cancer Hospital Care Center at Long Ridge
    • Torrington, Connecticut, United States, 06790
      • Smilow Cancer Hospital-Torrington Care Center
    • Trumbull, Connecticut, United States, 06611
      • Smilow Cancer Hospital Care Center-Trumbull
    • Waterbury, Connecticut, United States, 06708
      • Smilow Cancer Hospital-Waterbury Care Center
    • Waterford, Connecticut, United States, 06385
      • Smilow Cancer Hospital Care Center - Waterford
  • Rhode Island
    • Westerly, Rhode Island, United States, 02891
      • Smilow Cancer Hospital Care Center - Westerly

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Participants must have histologically confirmed metastatic ER-positive (> 10%), PR-positive or PR-negative, and HER2-negative (0 by immunohistochemistry [IHC] or if +1 or +2 by IHC, not amplified by fluorescence in situ hybridization [FISH]) breast cancer; ER positivity, PR positivity, and HER2 negativity as per the 2018 joint American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) guidelines.
• Participants must be starting CDK4/6 inhibitor and endocrine therapy as part of first-line therapy per standard of care and be previously CDK4/6 inhibitor-naïve.
• Participants must be enrolled prior to starting CDK4/6 inhibitor therapy.
• Participants must be ≥ 18 years of age.
• Participants must have an Eastern Cooperative Oncology Group (ECOG) Performance Status < 3.
• Willing and able to provide written informed consent for the trial.

Exclusion Criteria:

• Participants without evidence of metastatic disease prior to registration.
• Participants with prior use of CDK4/6 inhibitor therapy.
• Participants who are unable to provide informed consent for the trial.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Health services research (DiviTum-TKa); Patients undergo collection of blood samples per SOC on days 1, 15, and 28 of cycle 1, days 15 and 28 of cycle 2, days 15 and 28 of cycle 3, and day 28 of subsequent cycles for up to 12 cycles for analysis by DiviTum-TKa in the absence of disease progression or unacceptable toxicity.	Device: DiviTum-TKa; Analyze blood samples by DiviTum-TKa

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of patients with thymidine kinase activity (TKa) values that switch from profile 3 to profile 1 or 2 after medication compliance and drug-drug interaction assessment	Will be estimated using the two-sided 95% exact confidence interval (CI) using Clopper-Pearson method.	Immediately following counseling for medication compliance and adjustment of potential deleterious drug-drug interactions
Rate of improvement in CDK4/6 inhibitor response (i.e. moving from profile 3 to profiles 1 or 2)	Will be estimated using the two-sided 95% exact CI using Clopper-Pearson method.	At day 28 of cycles 2 and 3 immediately following counselling for medication compliance and removing potential deleterious drug-drug interactions

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical benefit rate (CBR) in patients with sub-optimal (profile 3) and optimal (profiles 1 and 2) CDK4/6 inhibitor response	CBR is defined as the total number of patients who achieve a complete response, partial response, or stable disease for 6 months or more from day 1 (D1) cycle 1 (C1). Comparisons between paired outcomes will be completed using the paired t-test or Wilcoxon signed-rank test for continuous parameters of interest, or McNemar's Chi-square test for categorical parameters of interest.	At day 28 of cycles 1 and 3
Progression free survival (PFS)	PFS is defined as the time from D1C1 to disease progression. Will be estimated using Kaplan-Meier method.	At 6, 12, and 18 months
CDK4/6 inhibitor response via TKa levels upon CDK4/6 inhibitor dose reductions or changes in CDK4/6 inhibitor regimen due to adverse events	Will estimate the two-sided 95% exact CI using Clopper-Pearson method.	Up to 2 years
Comparison of CDK4/6 inhibitor response profiles across the three CDK 4/6 inhibitors	Will be completed using the paired t-test or Wilcoxon signed-rank test for continuous parameters of interest, or McNemar's Chi-square test for categorical parameters of interest.	Up to 2 years

Collaborators and Investigators

• Sponsor: Yale University
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Mariya Rozenblit, Yale University

Study record dates

Study Major Dates

• Study Start (Actual): September 5, 2023
• Primary Completion (Actual): September 16, 2025
• Study Completion (Actual): September 16, 2025

Study Registration Dates

• First Submitted: August 22, 2024
• First Submitted That Met QC Criteria: August 22, 2024
• First Posted (Actual): August 27, 2024

Study Record Updates

• Last Update Posted (Estimated): October 8, 2025
• Last Update Submitted That Met QC Criteria: October 7, 2025
• Last Verified: October 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Skin Diseases; Breast Diseases; Breast Neoplasms
• Other Study ID Numbers: 2000033797 (Other Identifier: Yale University); P30CA016359 (U.S. NIH Grant/Contract); NCI-2024-01395 (Registry Identifier: CTRP (Clinical Trial Reporting Program))

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: No