Mirati Presents Data From Ongoing Phase 2 Clinical Trial Of Mocetinostat In Combination With Durvalumab At The SITC 33rd Annual Meeting

SAN DIEGO, Nov. 9, 2018 /PRNewswire/ -- Mirati Therapeutics, Inc. (NASDAQ: MRTX), a clinical-stage targeted oncology company, announced data from the ongoing Phase 2 clinical trial of mocetinostat in combination with durvalumab (IMFINZI^®) in non-small cell lung cancer (NSCLC) patients at the Society for Immunotherapy of Cancer (SITC) 33^rd Annual Meeting in Washington, D.C. The data will be presented today in a poster and also in an oral presentation on Sunday, November 11^th.

Highlights from the Oral Presentation

The clinical trial is a Phase 2 study evaluating the efficacy and safety of mocetinostat in combination with durvalumab, an anti-PD-L1 immune checkpoint inhibitor, in patients with NSCLC who have experienced documented disease progression following prior treatment with an immune checkpoint inhibitor. As of the data cut-off date of October 2, 2018:

• 29 patients were evaluable for response with at least one radiographic scan. Patients had a median of two lines of previous therapy.
• 12/29 evaluable patients demonstrated tumor reductions.
• 6/29 evaluable patients demonstrated tumor reductions of greater than 30%.
• 5/29 evaluable patients achieved a confirmed Partial Response (PR).
• 4/29 evaluable patients, including 2 responding patients, remained on treatment at the time of data cut-off.
• A preliminary Kaplan-Meier estimate of median duration of response was greater than 5 months.
• The combination has been well-tolerated and most adverse events (AEs) were grade 1 or 2.

"The combination of mocetinostat with durvalumab demonstrated clinical benefit in this difficult to treat population of checkpoint inhibitor refractory NSCLC patients," said Charles Baum, M.D., Ph.D., President and Chief Executive Officer at Mirati Therapeutics. "While these results are promising, we have made the strategic portfolio decision to prioritize sitravatinib for further development in the treatment of checkpoint inhibitor refractory patients and plan to explore collaborative opportunities to further develop mocetinostat." 

The Company recently announced plans to initiate a Phase 3 clinical trial comparing sitravatinib in combination with checkpoint inhibitor therapy to docetaxel in second line checkpoint inhibitor refractory NSCLC patients in the first half of 2019. In addition, the Company also announced plans to initiate a Phase 1/2 clinical trial of MRTX849, an oral inhibitor of KRAS G12C, in patients with NSCLC, colorectal cancer, and other solid tumors that harbor the G12C mutation. Trial initiation is planned for early 2019 after the investigational new drug (IND) allowance letter is received from the U.S. Food and Drug Administration (FDA) for the application that was filed in October 2018.

About Mocetinostat

Mocetinostat is an oral, Class I and IV selective histone deacetylase (HDAC) inhibitor. Inhibition of histone acetylation is predicted to enhance the recognition of tumor cells by anti-tumor T cells and reverse immunosuppressive factors in the tumor microenvironment. Mocetinostat is being evaluated in a Phase 2 clinical trial in combination with durvalumab (IMFINZI^®) in non-small cell lung cancer (NSCLC) patients who have experienced disease progression following prior treatment with a checkpoint inhibitor.

About Sitravatinib

Sitravatinib is a spectrum-selective kinase inhibitor that potently inhibits receptor tyrosine kinases (RTKs), including TAM family receptors (TYRO3, Axl, Mer), split family receptors (VEGFR2, KIT) and RET. As an immuno-oncology agent, sitravatinib is being evaluated in combination with nivolumab (OPDIVO^®), an anti-PD-1 checkpoint inhibitor, in patients who have experienced documented disease progression following treatment with a checkpoint inhibitor. Sitravatinib's potent inhibition of TAM and split family RTKs may overcome resistance to checkpoint inhibitor therapy through targeted reversal of an immunosuppressive tumor microenvironment, enhancing antigen-specific T cell response and expanding dendritic cell-dependent antigen presentation.

Sitravatinib is also being evaluated as a single agent in a Phase 1b expansion clinical trial emphasizing enrollment of patients whose tumors harbor specific mutations in the CBL protein. When CBL is inactivated by mutation, multiple RTKs, including TAM, VEGFR2 and KIT, are dysregulated and may act as oncogenic tumor drivers in NSCLC and melanoma. Sitravatinib potently inhibits these RTKs and is being investigated as a treatment option for cancer patients with CBL mutations.

About MRTX849

MRTX849 is an orally-available small molecule that potently and selectively inhibits a form of KRAS which harbors a substitution mutation (G12C). KRAS G12C mutations are present in approximately 14% of NSCLC adenocarcinoma patients and 5% of colorectal cancer patients. Tumors characterized by KRAS G12C mutations are commonly associated with poor prognosis and resistance to therapy, and patients with these mutations have few treatment options. MTRX849 has demonstrated broad-spectrum tumor regression in a large cohort of KRAS G12C positive, pre-clinical in-vivo human tumor models. MRTX849 demonstrated complete regression of tumors in a subset of models at well-tolerated dose levels. Early proof-of-concept clinical data is anticipated in 2019.

About Mirati Therapeutics

Mirati Therapeutics, Inc. is a clinical-stage oncology company developing product candidates to address the genetic, epigenetic and immunological promoters of cancer. Our precision oncology clinical programs utilize next-generation genomic testing to identify and select cancer patients who we believe would be most likely to benefit from targeted drug treatment. In immuno-oncology, we are advancing clinical programs where our product candidates have the potential to improve the immune environment of tumor cells and may enhance and expand the efficacy of existing cancer immunotherapy medicines when given in combination. Our pre-clinical programs include potentially first-in-class and best-in-class product candidates specifically designed to address mutations and tumors where few treatment options exist. We approach each of our discovery and development programs with a singular focus: to translate our deep understanding of the molecular drivers of cancer into better therapies and better outcomes for patients. For more information, visit www.mirati.com.

Forward Looking Statements

This press release contains forward-looking statements within the meaning of the U.S. Private Securities Litigation Reform Act of 1995. Any statements in this press release regarding the business of Mirati Therapeutics, Inc. ("Mirati") that are not historical facts may be considered "forward-looking statements," including without limitation statements regarding Mirati's development plans and timelines, potential regulatory actions, expected use of cash resources, the timing and results of clinical trials, and the potential benefits of and markets for Mirati's product candidates. Forward-looking statements are typically, but not always, identified by the use of words such as "may," "will," "would," "believe," "intend," "plan," "anticipate," "estimate," "expect," and other similar terminology indicating future results. Forward-looking statements are based on current expectations of management and on what management believes to be reasonable assumptions based on information currently available to them, and are subject to risks and uncertainties. Such risks and uncertainties may cause actual results to differ materially from those anticipated in the forward-looking statements. Such risks and uncertainties include without limitation potential delays in development timelines, negative clinical trial results, reliance on third parties for development efforts, changes in the competitive landscape, changes in the standard of care, as well as other risks detailed in Mirati's recent filings on Forms 10-K and 10-Q with the U.S. Securities and Exchange Commission. Except as required by law, Mirati undertakes no obligation to update any forward-looking statements to reflect new information, events or circumstances, or to reflect the occurrence of unanticipated events.

SOURCE Mirati Therapeutics, Inc.

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