Dose Defining Study For MK-2206 Combined With Gefitinib In Non Small Cell Lung Cancer (NSCLC)

2014-07-23 21:08:44 | BioPortfolio


This is a phase I study of MK2206 (an AKT inhibitor)and gefitinib in nonsmall cell lung cancer patients who failed prior chemotherapy and epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI). The patient population is enriched for EGFR mutations.

The purpose of this study is to determine whether it is safe to administered MK-2206 in combination with gefitinib in adult patients with locally advanced or metastatic non-small cell lung cancer. The second purpose of this study is to define the MTD (Maximum Tolerated Dose) of MK-2206 when combined with gefitinib.

A standard 3-3 dose escalation scheme of MK-2206 with fix dose gefitinib is used in this study.


Preclinical data from communication with Merck clinical and pre-clinical group support the application of MK2206 and an EGFR-TKI, and the synergistic effect of this combination. This proposed study is a phase I dose defining study to define the MTD (Maximum Tolerated Dose) of MK-2206 when combined with gefitinib.

MK-2206 is a potent, orally active, allosteric inhibitor of human AKT1, AKT2, and AKT3 with preclinical anti-tumor activity.

This is a Phase I, single-center, open-label, non-randomized, dose-escalation study in patients with locally advanced or metastatic NSCLC. Patients who previously failed and progressed through EGFR inhibitor such as erlotinib or gefitinib and up to one line of chemotherapy will be enrolled into the study. Patients will be administered with oral MK-2206 and a standard dose of EGFR inhibitor gefitinib.

This study will be conducted in three cohorts to identify a recommended Phase II dose (RP2D) of MK-2206 in combination with standard dose of gefitinib (250 mg QD). Cohorts of 3 patients will be enrolled sequentially on escalating doses of MK-2206 administered in combination with a standard dose of gefitinib. Patients will advance doses of MK2206 if 0/3 patients or 0-1/6 develop DLT (Dose-Limiting Toxicity). If 1/3 patient develops DLT, the cohort will be expanded to 6. If 2/6 patients developed DLT, the dose will be de-escalate to 90 mg Qwk. The highest dose cohort with 0-1/6 with DLT will be deemed as MTD and used as cohort expansion for a total of 15 patients.

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment


Non Small Cell Lung Cancer




National Taiwan University Hospital


Not yet recruiting


National Taiwan University Hospital

Results (where available)

View Results


Published on BioPortfolio: 2014-07-23T21:08:44-0400

Clinical Trials [4624 Associated Clinical Trials listed on BioPortfolio]

PIK3CA Mutation Stratified Trial of MK-2206 in Recurrent or Advanced Endometrial Cancer

MK-2206 is a drug that may stop cancer cells from growing. MK-2206 blocks a signal inside the cell that can cause abnormal cell growth. This drug has been used in other research studies ...

Study of Safety, Efficacy and Pharmacokinetics of CT-707 in Patients With ALK-positive Non-small Cell Lung Cancer

This is a Phase I study of the ALK/FAK/Pyk2 inhibitor CT-707 in patients with ALK-positive non-small cell lung cancer. The purpose of the study is to determine the MTD/RP2D of CT-707 and ...

Non-small Cell Lung Cancer Registry

This trial will evaluate two separate groups of patients with stage IIIB/IV non-small cell lung cancer. The objective of Group 1 is to investigate an FDA-approved drug in stage IIIB/IV non...

FR901228 in Treating Patients With Refractory or Progressive Small Cell Lung Cancer or Non-Small Cell Lung Cancer

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. PURPOSE: Phase II trial to study the effectiveness of FR901228 in t...

A Study to Explore Prognoses of the Patients With N2 Non-small Cell Lung Cancer

The trial was designed to compare the effectiveness of radical resections of lung cancer plus adjuvant chemotherapies and perioperative chemotherapies in the patients with N2 non-small cel...

PubMed Articles [31915 Associated PubMed Articles listed on BioPortfolio]

Expression of HNF4G and its potential functions in lung cancer.

The hepatocyte nuclear factor 4 gamma (HNF4G), a member of orphan nuclear receptors, is up-regulated and functions as an oncoprotein in bladder cancer. In the present study, we observed that HNF4G exp...

Genomic Features of Response to Combination Immunotherapy in Lung Cancer.

In this issue of Cancer Cell, Hellmann et al. describe in two clinical trials the importance of tumor mutational burden as an independent predictive marker for outcomes with combination nivolumab plu...

KMT2D Mutation Is Associated With Poor Prognosis in Non-Small-Cell Lung Cancer.

Mixed-lineage leukemia protein 2 (MLL2 or KMT2D) is a histone methyltransferase whose mutation has been associated with a poor prognosis in cancer. We compared the characteristics and significance of ...

Somatostatin and CXCR4 expression patterns in adenocarcinoma and squamous cell carcinoma of the lung relative to small cell lung cancer.

Lung cancer is highly prevalent and has an especially poor prognosis. Thus, new diagnostic and therapeutic targets are necessary. Two potential targets are somatostatin receptors (SST), which are over...

A-674563, a putative AKT1 inhibitor that also suppresses CDK2 activity, inhibits human NSCLC cell growth more effectively than the pan-AKT inhibitor, MK-2206.

AKT is a serine-threonine kinase implicated in tumorigenesis as a central regulator of cellular growth, proliferation, survival, and metabolism. Activated AKT is commonly overexpressed in non-small ce...

Medical and Biotech [MESH] Definitions

Malignant neoplasm arising from the epithelium of the BRONCHI. It represents a large group of epithelial lung malignancies which can be divided into two clinical groups: SMALL CELL LUNG CANCER and NON-SMALL-CELL LUNG CARCINOMA.

A form of highly malignant lung cancer that is composed of small ovoid cells (SMALL CELL CARCINOMA).

A heterogeneous aggregate of at least three distinct histological types of lung cancer, including SQUAMOUS CELL CARCINOMA; ADENOCARCINOMA; and LARGE CELL CARCINOMA. They are dealt with collectively because of their shared treatment strategy.

A quinazoline derivative and ANTINEOPLASTIC AGENT that functions as a PROTEIN KINASE INHIBITOR for EGFR associated tyrosine kinase. It is used in the treatment of NON-SMALL CELL LUNG CANCER.

A cell adhesion molecule that contains extracellular immunoglobulin V and C2 domains. It mediates homophilic and heterophilic cell-cell adhesion independently of calcium, and acts as a tumor suppressor in NON-SMALL-CELL LUNG CANCER (NSCLC) cells. Its interaction with NATURAL KILLER CELLS is important for their cytotoxicity and its expression by MAST CELLS plays a role in their interaction with neurons; it may also function in synapse assembly, nerve growth and differentiation.

More From BioPortfolio on "Dose Defining Study For MK-2206 Combined With Gefitinib In Non Small Cell Lung Cancer (NSCLC)"

Quick Search


Relevant Topics

Clincial Trials
In a clinical trial or interventional study, participants receive specific interventions according to the research plan or protocol created by the investigators. These interventions may be medical products, such as drugs or devices; procedures; or change...

Pulmonary relating to or associated with the lungs eg Asthma, chronic bronchitis, emphysema, COPD, Cystic Fibrosis, Influenza,  Lung Cancer, Pneumonia, Pulmonary Arterial Hypertension, Sleep Disorders etc Follow and track Lung Cancer News ...

Searches Linking to this Trial