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

NCT02185690 | Completed Phase 1 Results DMC FDA Drug

• 1 other identifier: CMEK162ACA02T
• Study Type: interventional
• Target: 13
• Locations: 1 country
• Sites: 4

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.

Conditions

Lungcancer

Keywords

Lung cancer; Non small cell lung cancer; non squamous; pemetrexed; carboplatin; binimetinib; chemotherapy; combination chemotherapy; Phase 1; Princess Margaret Cancer Centre; carcinoma

Outcome Measures

Primary Outcomes (1)

• Recommended Dose in Milligrams Per Day for Binimetinib.

  To determine the recommended dose in milligrams per day of the combination of MEK162 with standard therapy pemetrexed and carboplatin as determined by toxicity.

  22 weeks

Secondary Outcomes (1)

• Objective Response Rate (ORR) as Per RECIST v1.1.

  22 weeks

Other Outcomes (2)

• Exploratory Analysis of Objective Response Rate, KRAS Mutation Sub-type.

  22 weeks

• Progression Free Survival Rate

  26 weeks

Study Arms (1)

Binimetinib efficacy/safety

OTHER

This is a Phase I/Ib, open-label, dose-escalation, multi-center, non-randomized study designed to evaluate the safety and tolerability of oral Binimetinib in combination with carboplatin and pemetrexed. Phase I part A standard 3+3 dose-escalation will be used to determine the maximum administered dose (MAD) and the RP2D for the combination in subjects with advanced non-squamous lung carcinoma. Phase Ib part Once RP2D has been identified, an expansion cohort will be accrued; these patients will be stratified by KRAS genotype. The RP2D will be expanded by enrolling additional patients, stratified by KRAS genotype, to a total of 30 patients eligible for the safety set (including those treated at the same dose combination in the dose-escalation phase of the study who are eligible for the safety set) to be evaluated for safety, tolerability, pharmacokinetics and biologic activity of MEK162.

Drug: Binimetinib; Drug: Pemetrexed; Drug: Carboplatin

Interventions

Binimetinib DRUG

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.

Also known as: MEK162

Binimetinib efficacy/safety

Pemetrexed DRUG

4-6 cycles given intravenously in combination with carboplatin as per standard therapy.

Also known as: Alimta

Binimetinib efficacy/safety

Carboplatin DRUG

4-6 cycles of intravenous Carboplatin in combination with Pemetrexed as per standard therapy.

Also known as: Paraplatin AG

Binimetinib efficacy/safety

Eligibility Criteria

• Age: 18 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subjects eligible for enrolment on the study must meet all of the following criteria:
• Patients with histologically confirmed non-squamous EGFR wild-type, ALK-rearrangement negative carcinoma of lung. Patients with neuroendocrine carcinoma, mixed small and non-small cell carcinoma or squamous carcinoma are not eligible.
• Tissue available for KRAS mutation status analysis.
• Patients must have metastatic disease (Incurable stage IIIB/stage IV).
• Patients must have clinically and/or radiographically documented measurable disease. At least one site of disease must be unidimensionally measurable by RECIST v1.1 as follows (Eisenhauer et al.):
• CT-scan, physical exam ≥10 mm Chest X-ray ≥20 mm Lymph node short axis ≥15 mm
• All radiology studies must be performed within 28 days prior to registration (35 days if negative).
• Lesions in previously irradiated areas should not be selected unless there is clear evidence of progression in such lesions.
• Patients may not have received any prior systemic treatment for metastatic NSCLC. Patients who have received adjuvant treatment or chemoradiation for stage III disease should have completed this ≥12 months prior to study enrollment.
• Patients with stable CNS metastases are permitted if stability of disease is documented with imaging ≥28 days after treatment completion, are and off corticosteroids by day 1 of study treatment.
• Patients may have had prior malignancy if definitively treated and/or, in the opinion of the investigator, the only active malignancy is NSCLC. Patients with mixed small cell lung cancer histology are excluded. Patients who have received radiotherapy to \>30% bone marrow are excluded. Consult PI if unsure whether second malignancies meet requirements specified above.
• In patients treated for other malignancy, all prior treatment-related toxicities must be CTCAE v4.0 ≤ Grade 1 (except alopecia) at the time of enrollment.
• Able to swallow and retain oral medication and does not have any clinically significant gastrointestinal abnormalities that may alter absorption such as malabsorption syndrome or major resection of the stomach or bowels.
• Patients receiving medications or substances that are inhibitors or inducers of CYP1A2, CYP2A19, CYP2B6, CYP3A4 and/or UGT1A1 and UGT1A9 are eligible but these drugs must be used with caution (Appendix C).
• Because the lists of these agents are constantly changing, it is important to regularly consult a frequently-updated list such as http://medicine.iupui.edu/clinpharm/ddis/table.aspx;

You may not qualify if:

• History or current evidence/risk of retinal vein occlusion (RVO) or central serous retinopathy (CSR):
• History of RVO or CSR, or predisposing factors to RVO or CSR (e.g., uncontrolled glaucoma or ocular hypertension, uncontrolled systemic disease such as hypertension, diabetes mellitus, or history of hyperviscosity or hypercoagulability syndromes). Patients with prior deep venous thrombosis or pulmonary embolism are permitted.
• Visible retinal pathology as assessed by ophthalmologic exam that is considered a risk factor for RVO or CSR such as:
• Evidence of new optic disc cupping
• Evidence of new visual field defects on automated perimetry
• Intraocular pressure \>21mmHg as measured by tonography
• Any serious and/or unstable pre-existing medical (aside from malignancy exception), psychiatric disorder, or other conditions that could interfere with subjects' safety, obtaining informed consent or compliance to the study procedures, in the opinion of the PI.
• History of interstitial lung disease or pneumonitis.
• Evidence of severe or uncontrolled systemic diseases (e.g., unstable or uncompensated respiratory, hepatic, renal metabolic or cardiac disease).
• Any factors that increase the risk of QTc prolongation or risk of arrhythmic events (e.g. congenital long QT syndrome, family history of long QT syndrome, hypokalemia) or baseline QTcB interval ≥480 msec.
• History of acute coronary syndromes (including myocardial infarction and unstable angina), coronary angioplasty, or stenting within the past 6 months or cardiac metastases.
• History or evidence of current clinically significant uncontrolled arrhythmias.
• History or evidence of current ≥Class II congestive heart failure as defined by New York Heart Association (NYHA).
• Known positivity for Hepatitis B surface antigen or Hepatitis C antibody.
• Known Human Immunodeficiency Virus (HIV) infection.

Sponsors & Collaborators

• University Health Network, Toronto: lead
• Novartis Pharmaceuticals: collaborator

Study Sites (4)

Cross Cancer Institute

Edmonton, Alberta, T6G1Z2, Canada

Location

Juravinski Cancer Centre

Hamilton, Ontario, L8V 5C2, Canada

Location

The Ottawa Hospital Regional Cancer Centre

Ottawa, Ontario, K1G 3Y9, Canada

Location

Princess Margaret Cancer Centre

Toronto, Ontario, M5G2M9, Canada

Location

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Related Links

• Publication

MeSH Terms

Conditions

Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Carcinoma

Interventions

binimetinib; Pemetrexed; Carboplatin

Condition Hierarchy (Ancestors)

Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type

Intervention Hierarchy (Ancestors)

Guanine; Hypoxanthines; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Glutamates; Amino Acids, Acidic; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Dicarboxylic; Coordination Complexes; Organic Chemicals

Results Point of Contact

• Title: Dr. Natasha Leighl, Sponsor-Investigator, Division of Medical Oncology
• Organization: Princess Margaret Cancer Centre, University Health Network

natasha.leighl@uhn.ca

416-946-4645

Study Officials

• Natasha Leighl, MD

  UHN - Princess Margaret Cancer Centre

  PRINCIPAL INVESTIGATOR

• Amit Oza, MD

  Princess Margaret Cancer Centre Drug Development Program

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 9, 2014
• First Posted: July 9, 2014
• Study Start: March 7, 2017
• Primary Completion: July 4, 2019
• Study Completion: July 4, 2019
• Last Updated: August 21, 2025
• Results First Posted: August 21, 2025

Record last verified: 2025-08

Locations

CA (4)