Mirati Therapeutics Doses First Patient in Expansion Cohorts of Phase 1b Trial of MGCD265 in Genetically Selected Patients

Mirati Therapeutics, Inc.

today announced that the first patient with Non-Small Cell Lung Cancer (NSCLC) has been dosed in a Phase 1b clinical trial of MGCD265 in selected patients exhibiting genetic alterations of MET or Axl. In this segment of the study, one of the expansion cohorts will enroll patients with NSCLC and another will enroll patients with other solid tumors. Both cohorts will enroll only those patients that have specific MET driver mutations including MET gene point mutations, gene amplification, and MET or Axl gene rearrangements. "In the dose escalation phase of this trial, we identified an optimal dose that achieved serum levels that we believe will result in greater than 90% inhibition of MET and Axl," said Charles M. Baum, M.D., Ph.D., president and CEO of Mirati. "We are focused on patients whose tumors harbor the specific MET and Axl genetic alterations that MGCD265 is designed to treat. By selecting and treating only those patients who carry the targeted mutations, there is strong rationale that we'll see proof of concept based on a high overall response rate in early 2015 that supports accelerated drug development." MGCD265 is an orally bioavailable tyrosine kinase inhibitor that selectively targets MET and Axl. Genetic alterations in these targets have been implicated as drivers of tumor growth and disease progression in NSCLC, and other solid tumors. MET and Axl are also implicated as drivers of tumor progression in patients whose tumors have become resistant to EGFR inhibitors such as Tarceva, Iressa and Erbitux. Therefore, the combination of MGCD265 with EGFR inhibitors may also address acquired resistance to agents targeting EGFR. The open-label Phase 1b study of MGCD265 is expected to enroll up to 60 patients with one cohort focused on NSCLC and another that will enroll patients with advanced solid tumors that carry genetic alterations in MET or Axl. The purpose of this trial is to evaluate the safety and efficacy of MGCD265 administered to selected patients with specific activating MET driver mutations, MET gene amplification, and MET or Axl gene rearrangements. Additional information about this clinical trial of MGCD265 is available at www.clinicaltrials.gov using identifier: NCT00697632. About NSCLC Despite available treatment options, the overall five year survival rate for patients with NSCLC is only 16.8% and NSCLC results in the greatest number of cancer deaths in the United States. Moreover, the five year over survival rate for Stage 4 metastatic disease is a mere 4.0% (SEER Lung and Bronchus Cancer-2011). Over recent years, new therapies have been approved that target gene pathways implicated in progression of NSCLC, including EGFR kinase inhibitors, EML4-ALK inhibitors, and VEGF monoclonal antibodies. However, these targets represent only a fraction of the growing list of cancer genes that play a role in NSCLC. Given these factors, there remains a significant unmet medical need to develop new therapies that inhibit multiple targets, particularly those that also inhibit novel targets for which no therapy exists. About MET and Axl MET and Axl are receptor tyrosine kinases (RTK) that play key roles in the pathogenesis of several human cancers and are critical mediators of tumor cell survival and metastatic progression, as well as the inappropriate formation of blood vessels (angiogenesis) that nourish the tumors. The MET RTK is expressed in a wide variety of epithelial cells and signaling activity is normally tightly controlled in healthy tissues. However, MET has been shown to be dysregulated by mutation, gene amplification, and/or overexpression in NSCLC and other cancers. Dysregulation of the MET pathway is implicated in increased tumor cell proliferation, invasive growth, tumor angiogenesis, and metastatic progression of these cancers. In addition, MET has been implicated in evasive resistance to both chemotherapeutics and targeted therapies including VEGF pathway inhibitors, EGF receptor inhibitors, and Raf inhibitors. Axl is an oncogenic RTK that is also normally involved in the regulation of cell growth and survival but is dysregulated in multiple human cancers. Studies in recent years have shown that Axl expression is correlated with clinical stage and lymph node status in NSCLC, and involved in the mechanism of resistance to EGFR inhibitors such as Tarceva®. Axl is expressed in other tumor types and may be important in Renal Cell Carcinoma, Hepatocellular Carcinoma, Head and Neck, and other cancers.