Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
BEZ235+ Trastuzumab Phase l/Phase ll · 1 trial · 2 indications
DLT is defined as treatment-related toxicity (classified according Common Toxicity Criteria for Adverse Events (CTCAE) Version 4) occurring during the first 28 treatment days and meeting specific protocol-predefined criteria. The information will be integrated in a Bayesian logistic regression model with overdose control to estimate the maximum tolerated dose (MTD)
PFS is defined as the time from randomization until objective tumor progression or death from any cause. Radiological assessments will be performed every 6 weeks for the first 36 weeks after treatment start, then every 12 weeks.
| Arm | Type | Description |
|---|---|---|
| BEZ235 + Trastuzumab (Phase l /Phase ll) | EXPERIMENTAL | Phase l: Eligible patients will receive increasing doses of oral BEZ235 administered on a continuous twice daily (BID) schedule + weekly trastuzumab at a fixed dose of 2 mg/kg. Treatment will be organized into cycles of 28 days. Phase ll: Eligible patients will receive weekly trastuzumab (2 mg/kg) + oral BEZ235 on a continuous twice daily (BID schedule) at the MTD or RP2D. Treatment will be organized into cycles of 21 days. |
| Lapatinib + Capecitabine (Phase II) | ACTIVE_COMPARATOR | Eligible patients will receive lapatinib (1250 mg given orally once daily on days 1 through 21) in combination with capecitabine (2000 mg/m2/day administered orally in 2 doses approximately 12 hours apart on days 1 through 14). Treatment will be organized into cycles of 21 days . |
| Name | Type | Description |
|---|---|---|
| BEZ235 + Trastuzumab Phase l/Phase ll) | DRUG | Phase l: Patients will receive increasing doses of oral BEZ235 (BID) together with standard weekly trastuzumab at a fixed dose. BEZ235 doses will be escalated in cohorts of 3 to 6 patients guided by an adaptive Bayesian logistic regression model with overdose control until MTD/RP2D has been established. Phase ll: If randomized to the trastuzumab + BEZ235 arm, patients will receive standard weekly trastuzumab in combination with oral BEZ235 (BID) at the MTD or RP2D and will continue on study treatment until PD, unacceptable toxicity or until other pre-defined discontinuation criteria are met. They will have regular safety assessments and will be evaluated for response to treatment according to RECIST every 2 cycles for the first 36 weeks then every 12 weeks until disease progression (or start of new anti-neoplastic therapy). |
| Lapatinib + Capecitabine (Phase II) | DRUG | If randomized to the lapatinib + capecitabine treatment arm, patients will receive standard lapatinib plus capecitabine until PD, unacceptable toxicity or until other pre-defined discontinuation criteria are met. Patients will have regular safety assessments and will be evaluated for response to treatment according to RECIST every 2 cycles for the first 36 weeks then every 12 weeks until disease progression (or start of new anti-neoplastic therapy). After progression, survival f-up will continue. All patients participating in the Phase II part of the study will be required to have available archival or fresh tumor tissue for biomarker analysis prior to treatment start |
Inclusion Criteria: * Patient is a female ≥ 18 years of age * Patient has a histologically and/or cytologically confirmed diagnosis of HER2-positive invasive breast cancer with inoperable locally advanced or metastatic disease * Patients with controlled or asymptomatic CNS metastases are eligible *...
BEZ235 is an investigational small molecule being studied in oncology for multiple tumor types, including pancreatic neuroendocrine tumors (pNET), advanced solid tumors, breast cancer, locally advanced breast cancer (LABC), castration-resistant prostate cancer, and metastatic or locally advanced solid tumors. It is not approved and remains in clinical development.
BEZ235 is being developed by Novartis AG, a global pharmaceutical company traded on the New York Stock Exchange under the ticker NVS. The drug is an investigational small molecule in the oncology therapeutic area.
BEZ235 is in Phase 1 clinical development. All completed trials for the drug are Phase 1 studies. It is investigational and has not received FDA approval, as it remains under clinical investigation for various solid tumor indications.
BEZ235 has been studied in several completed Phase 1 trials, including NCT00620594 in advanced solid malignancies and breast cancer, NCT01195376 in Japanese patients with advanced solid tumors, NCT01471847 in HER2-positive breast cancer with trastuzumab, and NCT01634061 in castration-resistant prostate cancer with abiraterone acetate.
BEZ235 is the primary name for this investigational drug. No alternative names have been established in the clinical trial data, so it is consistently referred to as BEZ235 across studies.