NCT02185690

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

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 13 (actual)
• Sponsor: University Health Network, Toronto · Academic / Other
• Sex: All
• Age: 18 Years – 90 Years
• Healthy volunteers: Not accepted

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.

Conditions

• Lungcancer

Interventions

Type	Name	Description
DRUG	Binimetinib	Continuous MEK162 with dose escalation until the Recommended Phase 2 dose (RP2D) one dose level below the Maximum administered dose (MAD) or progression of disease. MEK162 tablets 15 mg strength will be taken orally on a BID dose schedule.
DRUG	Pemetrexed	4-6 cycles given intravenously in combination with carboplatin as per standard therapy.
DRUG	Carboplatin	4-6 cycles of intravenous Carboplatin in combination with Pemetrexed as per standard therapy.

Timeline

• Start date: 2017-03-07
• Primary completion: 2019-07-04
• Completion: 2019-07-04
• First posted: 2014-07-09
• Last updated: 2025-08-21
• Results posted: 2025-08-21

Locations

4 sites across 1 country: Canada

Regulatory

• FDA-regulated drug study