This is a prospective study to assess the impact of biomarker driven, early therapeutic switching and delayed imaging with the incorporation of DiviTum® serum TK1 activity ("DiviTum® TKa") in patients with HR positive, HER-2 negative metastatic or unresectable breast cancer. Patients will receive first-line treatment with a CDK4/6 inhibitor (CDK4/6i) and endocrine therapy. All patients will have blood drawn for thymidine kinase activity (TKa) testing at baseline and at C1D15. Patients who are found to have a lack of TKa suppression at C1D15 will be recommended to switch to an alternative therapy. Patients with suppressed C1D15 TKa levels will continue on CDK4/6i and endocrine therapy until clinical progression. Patients with TKa which remains suppressed will be recommended to delay restaging scans from 24 weeks to 36 weeks.
The investigators hypothesize that a patient's TKa level at C1D15 is prognostic for progression-free survival (PFS) on a CDK4/6 inhibitor and early therapeutic switching in patients with a lack of C1D15 TKa suppression will be associated with prolonged PFS.
Patients
Diagnosis of metastatic or advanced unresectable invasive breast cancer that is hormone receptor-positive (HR+) and HER2-negative.
Planned to initiate standard of care first-line therapy with FDA-approved endocrine therapy plus CDK4/6 inhibitor for the stated diagnosis at the time of study enrollment. Ribociclib is the preferred CDK4/6 inhibitor. In the event this drug cannot be obtained due to insurance authorization or if there are specific side effect profile concerns from the treating physician, an alternative CDK4/6 inhibitor is allowed.
Any prior therapy for early stage breast cancer is allowed, including endocrine therapy and chemotherapy.
Patients
Receipt of any prior cytotoxic chemotherapy line for metastatic disease. There will be no limit to chemotherapy use in the neoadjuvant or adjuvant setting.
Patients with a prior or concurrent malignancy are excluded unless that malignancy's natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial.
Concurrent participation in any investigational therapeutic trial for treatment of metastatic breast cancer.
Parallel
DiviTum® TKa assay
DeviceWill be utilized for determination of serum enzymatic activity of TK1 according to the manufacturer's instructions
CDK4/6 + Endocrine therapy
DrugFDA-approved endocrine therapy plus CDK4/6 inhibitor. Ribociclib is the preferred CDK4/6 inhibitor. In the event this drug cannot be obtained due to insurance authorization or if there are specific side effect profile concerns from the treating physician, an alternative CDK4/6 inhibitor is allowed.
Progression-free survival (PFS) in patients who remain on CKD4/6i (patients with suppressed TKa levels at cycle 1 day 15)
. PFS in patients with suppressed TKa levels is defined as from the start date of receiving CDK4/6i to the end date of CDK4/6i or last date on CDK4/6i if the treatment on CDK4/6i is still ongoing or date of death if death occurs on treatment.
Clinical benefit rate (CBR) in patients who remain on CDK4/6i
CBR is defined as total number (or percentage) of patients who achieved a complete response, partial response, or had stable disease for 6 months or more.
Progression-free survival (PFS) in patients who switch to an alternate therapy (patients with unsuppressed TKa levels at cycle 1 day 15)
PFS in patients with unsuppressed TKa levels is defined as from the start date of receiving CDK4/6i to the end date of next-line therapy or last date on next-line if the treatment on next-line therapy is still ongoing or date of death if death occurs on treatment.
Feasibility (compliance rate) in patients with suppressed TKa level at cycle 1 day 15
-Feasibility defined as compliance rate: \*\*Patients with suppressed TKa at C1D15, C2D1, C4D1 and 24 weeks: compliance is defined as this subset of physicians and patients who delay restaging scans from 24 weeks to 36 weeks.
Feasibility (compliance rate) in patients with unsuppressed TKa level at cycle 1 day 15
-Feasibility defined as compliance rate: \*\*Patients with unsuppressed TKa at C1D15: compliance is defined as subset of physicians and patients following protocol recommendation to switch to next line of treatment.
Baseline TKa level to predict overall survival (OS) on first-line CDK4/6i
OS is defined as from the start date of receiving CDK4/6i to the date of death or date of last follow up.
Baseline TKa level to predict overall survival (OS) on later lines of therapy
OS is defined as from the start date of receiving CDK4/6i to the date of death or date of last follow up.
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Washington University School of Medicine
Lead sponsor
Biovica
Collaborator
