Safety, Pharmacokinetics and Pharmacodynamics of BKM120 Plus MEK162 in Selected Advanced Solid Tumor Patients

Study Overview
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Brief Summary
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This is an open label, dose finding, phase Ib clinical trial to determine the maximum tolerated dose (MTD) and/or the recommended phase II dose (RP2D) of the orally administered phosphatidylinositol 3'-kinase (PI3K) inhibitor BKM120 in combination with the MEK1/2 inhibitor MEK162. This combination will be explored in patients with epidermal growth factor receptor (EGFR) mutant non-small cell lung cancer (NSCLC) which has progressed on EGFR inhibitors and triple negative breast cancer, as well as pancreatic cancer, colorectal cancer, malignant melanoma, NSCLC, and other advanced solid tumors with KRAS, NRAS, and/or BRAF mutations. Dose escalation will be guided by a Bayesian logistic regression model with overdose control. At MTD or RP2D, two expansion arms will be opened in order to further assess safety and preliminary anti-tumor activity of the combination of BKM120 and MEK162. Study drugs will be administered once daily orally on a continuous schedule. A treatment cycle is defined as 28 days.

Official Title
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A Phase Ib, Open-label, Multi-center, Dose-escalation and Expansion Study of an Orally Administered Combination of BKM120 Plus MEK162 in Adult Patients With Selected Advanced Solid Tumors

Conditions
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Advanced Solid Tumors, Selected Solid Tumors

Intervention / Treatment
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* Drug: BKM120 + MEK162


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically/ cytologically confirmed, advanced non resectable solid tumors Measurable or non-measurable, but evaluable disease as determined by RECIST Exclusion Criteria: Patients with primary CNS tumor or CNS tumor involvement. Diabetes mellitus Unacceptable ocular/retinal conditions

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: BKM120 + MEK162<br> | Drug: BKM120 + MEK162<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Dose Limiting Toxicities |  | during Cycle 1 of treatment with BKM120 and MEK162 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with adverse events and serious adverse events. |  | from Cycle 1 Day 1 until treatment discontinuation | 
| Overall response rate, duration of response, time to response and progression free survival |  | every 8 weeks of treatment | 
| Time versus plasma concentration profiles of BKM120 and MEK162 |  | during the first cycle of treatment on Cycle 1 Day 1 and Cycle 1 Day 15 | 
| Treatment -induced PI3K and MEK/ERK pathway signaling inhibition and evidence of biological activity in tumor. |  | during the first cycle of treatment on Cycle 1 Day 15 and at disease progression | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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BKM120, MEK162, RAS RAF mutations, triple negative breast cancer, pancreatic cancer, ovarian cancer, NSCLC progressed on EGFR TKI, PI3K inhibitor, MEK inhibitor