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PI3K inhibitor BYL719 · 1 trial · 6 indications
DLTs of BYL719 in combination with T-DM1 will be assessed using National Cancer Institute's Common Toxicity Criteria for adverse events version 4.0 (except for hyperglycemia). A DLT is described any grade 3 or higher, clinically significant toxicity (excluding alopecia) experienced during the first 21 days following first dose of BYL719 that is determined to be at least possibly related to study medication. Lower grades may also be considered DLTs if they lead to a dose interruption of more than 7 consecutive days of BYL719. In general adverse events (AEs) will be graded according to the following: Grade 1 Mild AE Grade 2 Moderate AE Grade 3 Severe AE Grade 4 Life-threatening or disabling AE Grade 5 Death related to AE
Safety of BYL719 in combination with T-DM1 will be assessed during the first 21 days (1 cycle=21 days) which will assist in providing the MTD. Adverse Events including dose limiting toxicities (DLT), changes in physical findings, or clinical laboratory results as well as cardiac toxicity (changes in cardiac function, which will be measured by use of echocardiogram or MUGA scan) will be evaluated. For each dose level, 3 patients will be treated. If none (0 of 3) show a DLT, dose will be escalated for the next cohort of patients. If 2 or 3 have a DLT, then the previous dose will be considered the MTD. If 2 or 3 in cohort 1 (starting dose) experience a DLT, then the dose in -1 cohort will be used. If 1 of 3 patients has a DLT, then an additional 3 patients will be added to that dose level. If 1 of 6 has a DLT, then the dose will be escalated. If 2 of 6 have a DLT, then this dose will be considered the MTD. If 3 or more of 6 have a DLT, then the previous dose will be the MTD.
| Arm | Type | Description |
|---|---|---|
| Treatment (PI3K inhibitor BYL719, ado-trastuzumab emtansine) | EXPERIMENTAL | Patients receive PI3K inhibitor BYL719 PO daily on days 1-21 and ado-trastuzumab emtansine IV over 30-90 minutes on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. |
| Name | Type | Description |
|---|---|---|
| PI3K inhibitor BYL719 | DRUG | Given PO |
| ado-trastuzumab emtansine | BIOLOGICAL | Given IV |
| pharmacological study | OTHER | Correlative studies |
| laboratory biomarker analysis | OTHER | Optional correlative studies |
Inclusion Criteria: * Patients must have histologically-confirmed HER2-positive breast cancer that is locally advanced or metastatic (stage 4); ideally this should be from biopsy of the metastatic disease; however if this is not available, histologic confirmation from the primary tumor is acceptabl...
PI3K inhibitor BYL719 is an investigational small molecule being studied for HER2-positive breast cancer, specifically in patients with recurrent, stage IIIA, IIIB, IIIC, or stage IV disease who have progressed on prior trastuzumab and taxane treatment. It is being evaluated in combination with T-DM1 in a completed Phase 1 clinical trial.
PI3K inhibitor BYL719 targets the PI3K pathway, which is involved in cancer cell growth and survival. By inhibiting PI3K, the drug aims to block this signaling pathway in HER2-positive breast cancer cells. The drug is being studied in combination with T-DM1 for patients who have progressed on prior trastuzumab and taxane therapy.
PI3K inhibitor BYL719 is being developed by Novartis AG, a multinational pharmaceutical company traded on the New York Stock Exchange under the ticker symbol NVS. The drug is an investigational small molecule in Phase 1 clinical development for HER2-positive breast cancer.
PI3K inhibitor BYL719 is in Phase 1 clinical development. It is an investigational drug, not yet approved by regulatory authorities. The Phase 1 trial, NCT02038010, has been completed and enrolled 17 female patients with HER2-positive metastatic breast cancer who had progressed on prior trastuzumab and taxane treatment.
PI3K inhibitor BYL719 has been studied in one completed Phase 1 clinical trial, NCT02038010, titled "BYL719 + T-DM1 in HER2(+) Metastatic Breast Cancer Pts Who Progress on Prior Trastuzumab & Taxane Tx." The trial enrolled 17 female patients in the United States and was uncontrolled, meaning there was no comparator arm.