Spots Global Cancer Trial Database for A Phase I/Ib Study of MEK162, a MEK Inhibitor, in Combination With Carboplatin and Pemetrexed in Patients With Non-squamous Carcinoma of the Lung

Study Description

Brief Summary: MEK162 has shown significant inhibition of tumor growth as a single agent in NSCLC xenograft models in mice and human cancer cells in vitro, which have KRAS and/or other mutations. These data suggest that MEK162 may provide a potential benefit in cancer indications harboring these mutations. MEK162 is currently being investigated in phase I clinical testing and has been well tolerated up to an MTD of 45mg BID in cancer patients. There has been little change in survival benefit for patients with non-small cell lung cancer in recent years. Emerging new treatment options relying on molecular and genetic markers are being studied extensively. Thus, there has been a shift to manage non-small cell lung cancer with molecular targeted therapies in combination with standard chemotherapy. This study will be targeting patients with KRAS mutations.

Detailed Description: OBJECTIVES 1.1 Primary Objectives * To assess the safety of MEK162 administered in combination with carboplatin and pemetrexed as first line treatment in advanced non-small cell lung cancer (NSCLC). * To determine the recommended phase II dose (RP2D) of MEK162 to be used when given in a continuous dosing schedule together with pemetrexed and carboplatin administered on a 3-weekly schedule as first line treatment in advanced NSCLC. * To explore the efficacy (as measured by tumor response in the Phase Ib portion) of the combination of MEK162 in addition to pemetrexed and carboplatin in treatment-naïve patients with EGFR wild-type, ALK-rearrangement negative NSCLC of the lung. 1.2 Secondary Objectives * To characterize the population pharmacokinetics of MEK162 administered in combination with carboplatin and pemetrexed (Phase I). * To explore relationships between KRAS mutation (and sub-types) and additional genomic mutations and objective clinical response. 1.3 Trial End-points Primary Phase I • Development of dose-limiting toxicity (DLT), (defined in section 4.3) as measured with NCI CTC AE v4. Phase Ib • Objective response rate (ORR) as per RECIST v1.1. Secondary Phase I • Adverse events, serious adverse events, changes in hematology and chemistry values, vital signs, ECGs. Phase Ib * Evaluation of response rate (RR), progression-free survival (PFS) and disease control rate (DCR) for patients with and without KRAS mutation in tumor tissue. * Exploratory analysis of KRAS mutation sub-type. Exploratory end-points • A limited sampling strategy pharmacokinetic model will be used to ensure that the clearance of MEK162 is not influenced by the concurrent administration of pemetrexed-based chemotherapy.

Keywords

Eligibility

Minimum Age: 18 Years

Eligible Ages: ADULT, OLDER_ADULT

Sex: ALL

Healthy Volunteers: No

Locations

Contact Details

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