TK1 Activity Test for Breast Cancer

Recruiting at 1 trial location

Overseen By Nusayba Bagegni, M.D.

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Washington University School of Medicine

Must be taking: Endocrine therapy, CDK 4/6 inhibitors

Must not be taking: Cytotoxic chemotherapy

Disqualifiers: Concurrent investigational trial, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 2

Duration: 36 months

55 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new blood test, the DiviTum® TKa assay, to assist doctors in determining when to schedule imaging and other tests for individuals with metastatic breast cancer. The goal is to assess whether this test can reduce the number of routine check-ups, simplifying the process for patients. The trial seeks participants with hormone receptor-positive (HR+) and HER2-negative metastatic breast cancer who are about to start or are currently receiving a specific combination of therapies, including CDK 4/6 inhibitors (such as palbociclib, ribociclib, or abemaciclib). As an unphased trial, this study provides patients the chance to contribute to innovative research that could streamline their care routine.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, it seems that participants are expected to continue their current endocrine therapy and CDK 4/6 inhibitor treatment as part of the study.

What prior data suggests that the DiviTum® TKa assay is safe for use in monitoring breast cancer?

Research has shown that the DiviTum® TKa test, which measures enzyme activity in the blood, is safe and well-tolerated. This test helps monitor treatment effectiveness for patients with a specific type of advanced breast cancer. As a blood test, it avoids the risks associated with more invasive procedures.

Regarding CDK 4/6 inhibitors, many studies indicate they are generally safe for patients with advanced breast cancer. These drugs can extend patients' lives, though they might cause side effects like tiredness or nausea. Side effects can vary among individuals and different types of these drugs.

Both the test and the drugs are considered safe. CDK 4/6 inhibitors have a well-established safety record, as the FDA has approved them for treating breast cancer. Participants should discuss any concerns with their doctor to make informed decisions. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about the TK1 Activity Test for Breast Cancer because it offers a novel way to monitor treatment effectiveness using the DiviTum® TKa assay. Unlike traditional methods, which often rely on imaging or symptoms to assess how well a patient is responding to treatment, this test uses blood samples to measure an enzyme called thymidine kinase 1 (TK1) that reflects cancer cell activity. This approach allows for earlier and potentially more precise detection of changes in the disease, helping doctors make timely adjustments to treatment plans. By providing real-time data on how well a treatment is working, this test has the potential to optimize patient care and improve outcomes.

What evidence suggests that the DiviTum® TKa assay is effective for monitoring breast cancer?

Research shows that CDK 4/6 inhibitors, which participants in this trial may receive as part of their treatment plan, effectively treat advanced hormone receptor-positive breast cancer. Studies indicate that patients using these inhibitors live, on average, 31 to 54 months longer, significantly increasing life expectancy.

Additionally, the DiviTum® TKa test, used in this trial, measures the activity of an enzyme called thymidine kinase 1 (TK1), linked to cancer activity. Research has found that higher TK1 levels can help predict how well patients will respond to treatment. This test can help doctors better understand and manage the disease, potentially leading to improved outcomes. ^{4 6 7 8 9}

Who Is on the Research Team?

Nusayba Bagegni, M.D.

Principal Investigator

Washington University School of Medicine

Are You a Good Fit for This Trial?

This trial is for women under 60 with HR+ and HER2- metastatic breast cancer, starting or already on FDA-approved endocrine therapy plus CDK 4/6 inhibitors. They must have a life expectancy over 6 months, be post-menopausal or have suppressed ovarian function, and not be in any other investigational treatment trials. Prior early-stage breast cancer treatments are okay.

Inclusion Criteria

I can understand and am willing to sign a consent form.

I am under 60, have a uterus, and haven't had a period for 12 months or more.

I am currently a patient at Siteman Cancer Center under a doctor in this trial.

Exclusion Criteria

I have received chemotherapy for cancer that has spread.

If you have had or currently have another type of cancer that won't affect the study's evaluations, your doctor and the study leader will decide if you can join the trial.

Concurrent participation in any investigational therapeutic trial for treatment of metastatic breast cancer.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive 1st line therapy with endocrine therapy + any FDA-approved CDK 4/6 inhibitor, with serum samples analyzed using DiviTum® TKa at specified intervals

36 months

Baseline, Week 2, Week 4, Week 6, Week 8, Week 12, Week 16, Week 20, Week 24, and every 12 weeks thereafter

Follow-up

Participants are monitored for safety and effectiveness after treatment, with a focus on longitudinal changes in DiviTum® TKa value dynamics

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• DiviTum® TKa assay
• Study Care Plans

Trial Overview The study tests if monitoring patients using the DiviTum® TKa assay can influence doctors to space out routine restaging tests like tumor imaging. The goal is to see if this leads to fewer overall tests by extending intervals between them due to low disease progression rates in these patients.

How Is the Trial Designed?

Group I: Medical Oncologists Experimental Treatment 1 Intervention

-Will be completing the Study Care Forms at Baseline, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24 and every 12 weeks thereafter until disease progression or 36 months.

Group II: Cohort 2: Currently receiving first line therapy Experimental Treatment 1 Intervention

* 1st line therapy with endocrine therapy + any FDA-approved CDK 4/6 inhibitor for ≤ 24 months with stable disease * Serum samples (analyzed using DiviTum® TKa) at Baseline, Week 2, Week 4, Week 6, Week 8, Week 12, Week 16, Week 20, Week 24 and every 12 weeks thereafter until disease progression or 36 months. Treating physician will evaluate the patient \& review any updated results of the institutional standard of care monitoring tests. Following receipt of DiviTum® TKa value, the treating physician will review the preceding locked Study Care Plan and record any changes

Group III: Cohort 1: Scheduled to receive first line therapy Experimental Treatment 1 Intervention

* Scheduled to receive 1st line therapy with endocrine therapy + any FDA-approved CDK 4/6 inhibitor * Serum samples (analyzed using DiviTum® TKa) at Baseline, Week 2, Week 4, Week 6, Week 8, Week 12, Week 16, Week 20, Week 24 and every 12 weeks thereafter until disease progression or 36 months. Treating physician will evaluate the patient \& review any updated results of the institutional standard of care monitoring tests. Following receipt of DiviTum® TKa value, the treating physician will review the preceding locked Study Care Plan and record any changes

Study Care Plans is already approved in United States, European Union for the following indications:

Approved in United States as palbociclib (Ibrance) for:

• Hormone receptor-positive, HER2-negative metastatic breast cancer

Approved in United States as ribociclib (Kisqali) for:

• Hormone receptor-positive, HER2-negative metastatic breast cancer
• Early breast cancer

Approved in United States as abemaciclib (Verzenio) for:

• Hormone receptor-positive, HER2-negative metastatic breast cancer
• Early breast cancer

Approved in European Union as palbociclib (Ibrance) for:

• Hormone receptor-positive, HER2-negative metastatic breast cancer

Approved in European Union as ribociclib (Kisqali) for:

• Hormone receptor-positive, HER2-negative metastatic breast cancer
• Early breast cancer

Approved in European Union as abemaciclib (Verzenio) for:

• Hormone receptor-positive, HER2-negative metastatic breast cancer
• Early breast cancer

Who Is Running the Clinical Trial?

Washington University School of Medicine

Lead Sponsor

Trials

2,027

Recruited

2,353,000+

Biovica

Collaborator

Trials

2

Recruited

120+

Published Research Related to This Trial

Palbociclib has been approved for treating hormone receptor-positive advanced breast cancer due to its ability to improve progression-free survival when used with endocrine agents, highlighting its efficacy in this patient population.

Abemaciclib and ribociclib, two other CDK4/6 inhibitors, are in late-stage clinical development and may offer different benefits, such as single-agent activity and central nervous system penetration, which could influence treatment choices and patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical Development of the CDK4/6 Inhibitors Ribociclib and Abemaciclib in Breast Cancer. Barroso-Sousa, R., Shapiro, GI., Tolaney, SM.[2020]

In a phase I trial involving 26 Chinese patients with advanced cancers, abemaciclib was found to be well tolerated, with most treatment-emergent adverse events being mild (Grade 1 or 2), although 32% experienced neutropenia and 24% experienced thrombocytopenia.

The pharmacokinetic profile showed slow absorption and a half-life of about 24 hours, with a disease control rate of 68%, indicating preliminary antitumor activity, although no complete responses were observed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Randomized Phase I Study of Abemaciclib in Chinese Patients with Advanced and/or Metastatic Cancers. Zhang, J., Yang, N., Ji, D., et al.[2021]

A total of 1611 individual case safety reports were analyzed, revealing that palbociclib and ribociclib were associated with serious adverse drug reactions (ADRs) like leukopenia and thrombocytopenia, although most patients recovered from these conditions.

In contrast, abemaciclib was linked to mostly non-serious ADRs, indicating a potentially better safety profile, especially when combined with treatments like fulvestrant.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hematological Events Potentially Associated with CDK4/6 Inhibitors: An Analysis from the European Spontaneous Adverse Event Reporting System. Martins, V., Jesus, M., Pereira, L., et al.[2023]

The addition of CDK4 and 6 inhibitors (like abemaciclib, palbociclib, or ribociclib) to endocrine therapy significantly improves progression-free survival and response rates in patients with HR+ and HER2- metastatic breast cancer, establishing these inhibitors as a new standard of care.

Exploratory analyses suggest that abemaciclib may be particularly beneficial for women with poor prognosis indicators, although further confirmation is needed for these findings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Abemaciclib, a CDK4 and CDK6 inhibitor for the treatment of metastatic breast cancer. Martin, M., Garcia-Saenz, JA., Manso, L., et al.[2021]

Abemaciclib, a CDK4/6 inhibitor, significantly reduced levels of Ki67, a protein that indicates cell proliferation, in women with hormone receptor-positive, HER2-negative breast cancer.

The results from the phase II neoMONARCH trial suggest that using abemaciclib, either alone or with endocrine therapy, may be an effective neoadjuvant treatment for early-stage breast cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Abemaciclib Shows Promise for Early Breast Cancer. [2019]

All three FDA-approved CDK4/6 inhibitors (palbociclib, ribociclib, and abemaciclib) are equally effective for treating HR-positive, HER2-negative metastatic breast cancer, highlighting the need for strategies to choose and sequence these treatments.

Ongoing research is focused on identifying biomarkers to predict which patients will benefit most from CDK4/6 inhibitors, exploring whether to continue treatment after disease progression, and investigating new combinations and uses beyond HR+/HER2- metastatic breast cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Future perspectives and challenges with CDK4/6 inhibitors in hormone receptor-positive metastatic breast cancer. Bayraktar, S., Batoo, S., Al-Hattab, E., et al.[2021]

CDK4/6 inhibitors like palbociclib, ribociclib, and abemaciclib are effective treatments for hormone receptor-positive advanced breast cancer, with ribociclib and abemaciclib showing improved overall survival in clinical trials.

Abemaciclib is the only CDK4/6 inhibitor that has demonstrated sustained improvement in invasive disease-free survival in early breast cancer, highlighting differences in efficacy among these drugs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors: existing and emerging differences. Johnston, S., Emde, A., Barrios, C., et al.[2023]

CDK4/6 inhibitors, such as palbociclib, ribociclib, and abemaciclib, have significantly improved treatment outcomes for hormone receptor-positive and HER2-negative breast cancer, establishing themselves as key options in both first- and second-line therapies.

While these inhibitors effectively prolong overall survival and progression-free survival in patients, they are also associated with notable adverse events, highlighting the need for careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An Overview of the Safety Profile and Clinical Impact of CDK4/6 Inhibitors in Breast Cancer-A Systematic Review of Randomized Phase II and III Clinical Trials. Stanciu, IM., Parosanu, AI., Nitipir, C.[2023]

CDK 4/6 inhibitors, including palbociclib, ribociclib, and abemaciclib, have been established as standard treatment for hormone receptor-positive, HER2-negative metastatic breast cancer, significantly doubling the efficacy of endocrine therapies.

Common side effects of CDK 4/6 inhibitors include neutropenia and other non-hematological toxicities like liver impairment and diarrhea, highlighting the importance of clinical monitoring for patients undergoing this treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Management of Adverse Events Due to Cyclin-Dependent Kinase 4/6 Inhibitors. Ettl, J.[2020]

CDK4/6 inhibitors (palbociclib, ribociclib, and abemaciclib) significantly improve progression-free survival in patients with hormone receptor-positive HER2-negative metastatic breast cancer when used alongside endocrine therapy, with a consistent hazard ratio of around 0.5 across phase III trials.

These treatments are generally well tolerated, with manageable side effects; however, abemaciclib is associated with a higher incidence of diarrhea, while palbociclib and ribociclib are more likely to cause hematological toxicities.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CDK4/6 Inhibitors Expand the Therapeutic Options in Breast Cancer: Palbociclib, Ribociclib and Abemaciclib. Eggersmann, TK., Degenhardt, T., Gluz, O., et al.[2019]

Thymidine kinase 1 (TK1) activity in blood is a dynamic biomarker that can indicate how well patients with advanced breast cancer respond to palbociclib, with significant changes observed after treatment.

In a study of 46 patients, a decrease in TK1 activity after one cycle of palbociclib correlated with better progression-free survival, while an increase in TK1 activity was linked to worse outcomes, suggesting it could help identify patients needing treatment adjustments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Plasma Thymidine Kinase Activity as a Biomarker in Patients with Luminal Metastatic Breast Cancer Treated with Palbociclib within the TREnd Trial. McCartney, A., Bonechi, M., De Luca, F., et al.[2021]

CDK4/6 inhibitors, like palbociclib and ribociclib, significantly improve progression-free survival in metastatic HR+, HER2- breast cancer when combined with hormonal therapy, but do not significantly increase overall survival.

There is a critical need for biomarkers to identify which patients will benefit from CDK4/6 inhibitors, as many experience primary or secondary resistance, leading to a switch to chemotherapy within 6 months.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Ongoing Search for Biomarkers of CDK4/6 Inhibitor Responsiveness in Breast Cancer. Schoninger, SF., Blain, SW.[2023]

Citations

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2. nature.com nature.com/articles/s44276-024-00070-w

Real-world effectiveness of CDK 4/6 inhibitors in estrogen ... First-line median OS was 37.8 months (95% CI: 32.5–NA); 49.7 months (95% CI: 44.7–54.1); and 54.4 months (95% CI: 47.9–NA) for abemaciclib, ...

3. jmcp.org jmcp.org/doi/10.18553/jmcp.2025.25063

First-line cyclin-dependent kinase 4 and 6 inhibitors in ... Real-world effectiveness of CDK 4/6 inhibitors in estrogen-positive metastatic breast cancer. BJC Rep. 2024;2(1):44. Go to Citation. Crossref.

4. sciencedirect.com sciencedirect.com/science/article/pii/S2949820124000420

UK multicentre real-world data of the use of cyclin ... These data demonstrate that CDK4/6is are an effective and safe treatment for metastatic HR+/HER2− breast cancer. Efficacy was in line with trial data and other ...

5. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.e13053

Real-world data on the effectiveness and toxicity of CDK 4 ... The median OS was 31.4 months (95% CI: 20.7–45.6) for ribociclib versus 27.1 months (95% CI: 18.5–36.2) for palbociclib. Patients receiving ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39076428/

A Systematic Review and Network Meta-Analysis Our findings suggest a comparative cardiovascular safety trend among the three CDK4/6 inhibitors, but further research on direct comparisons is ...

7. sciencedirect.com sciencedirect.com/science/article/pii/S0305737223000786

Safety profile of cyclin-dependent kinase (CDK) 4/6 ... We conducted a systematic review and meta-analysis to assess the safety profile of combining CDK4-6i with palliative and ablative RT in both the metastatic and ...

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Efficacy and Safety of Cyclin-Dependent Kinase 4/6 ... CDK4/6 inhibitors can improve OS and PFS in patients with advanced breast cancer. The incidence of adverse effects may differ with drugs and with ethnicity.

9. esmoopen.com esmoopen.com/article/S2059-7029(24)01874-X/fulltext

Comparative overall survival of CDK4/6 inhibitors plus an ... Randomized controlled trials have shown inconsistent overall survival (OS) benefit among the three cyclin-dependent kinase 4/6 inhibitors ...