A Phase 1B, Multi-Center, Open Label, Dose Escalation Study of Oral LDE225 in Combination with BKM120 in Patients with Advanced Solid Tumors

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Investigator: Pamela N. Munster, MD
Sponsor: Novartis Oncology

Location(s): United States

Description

The purpose of this study is to determine the maximum dose of LDE225 and BKM120 that can be safely given together to patients and/or the dose that will be used in future studies. This study will also learn more about how the combination of these two investigational drugs may work for patients with certain cancers (specifically metastatic breast cancer, advanced pancreatic adenocarcinoma, metastatic colorectal cancer and recurrent glioblastoma multiforme).

The primary purpose of this study is to determine a combination maximum tolerated dose (MTD) and/or recommended dose for expansion (RDE) of LDE225 and BKM120 when co-administered orally in patients with advanced solid tumors. Adult patients, aged > 18 years with advanced solid tumors that have progressed despite standard therapy or for which no standard therapies exist will be eligible for this study.

In the dose escalation part of the study, four groups of patients with the following tumor types will be enrolled: recurrent GBM, metastatic breast cancer, metastatic CRC and advanced pancreatic adenocarcinoma. It is anticipated that approximately 45 patients will be enrolled in the dose escalation part. Approximately 15 GBM patients (maximum of 2 patients per dose level) will be enrolled to previously well-tolerated doses during dose escalation if no slot is available in a cohort under active testing. In the dose expansion part of the study, five groups of patients (approximately 15 patients per group) with the following tumor types will be enrolled: recurrent GBM, triple negative metastatic breast cancer, hormone receptor positive (ER+/PR+, and Her2-) metastatic breast cancer, gastric/gastroesophageal junction cancer, and a combined maximum of 15 patients with metastatic CRC or advanced pancreatic adenocarcinoma. The dose expansion will enroll approximately 75 patients. Accounting for patients who may withdraw or who may not meet the eligibility criteria, it is expected that this study will enroll approximately 120 patients.

This is a multi-center, open-label, dose finding, phase Ib study to determine the MTD and/or RDE for the combination of LDE225 plus BKM120, followed by an expansion part to further assess safety and preliminary efficacy of the combination in patients with advanced solid tumors that are frequently associated with dysregulated Hh and/or PI3K pathways, specifically triple negative metastatic breast cancer, hormone receptor positive (ER+/PR+, and Her2-) metastatic breast cancer, advanced pancreatic adenocarcinoma, metastatic CRC, recurrent GBM and gastric/gastroesophageal junction cancer patients. Patients will be treated daily on 28-day cycles. Dose escalation will be dependent on the available toxicity information (including adverse events that are not DLTs), PK, PD, and efficacy information, as well as the recommendations from the Bayesian Logistic Regression Model (BLRM).