Mirati Therapeutics Presents Phase 2 Data On Sitravatinib In Combination With Nivolumab In Urothelial Cancer At ESMO Virtual Congress

SAN DIEGO, Sept. 18, 2020 /PRNewswire/ -- Mirati Therapeutics, Inc. (NASDAQ: MRTX), a clinical-stage targeted oncology company, today announced updated clinical results from its Phase 2 study evaluating sitravatinib in combination with nivolumab (OPDIVO^®) in patients with advanced or metastatic urothelial carcinoma. Sitravatinib is an investigational multi-targeted tyrosine kinase inhibitor that distinguishes itself by potently targeting the TAM (TYRO3, Axl, Mer) and split (VEGFR2, KIT) family receptors. The combination of sitravatinib with nivolumab demonstrated promising clinical activity in checkpoint inhibitor-naïve, platinum-refractory patients. These data were presented today in a mini oral session at the European Society for Medical Oncology Virtual Congress (ESMO) 2020 by Dr. Pavlos Msaouel, M.D., Ph.D.

The ongoing, Phase 2, open-label, multicenter trial in patients with advanced or metastatic urothelial carcinoma includes multiple patient cohorts that are defined based on prior therapy and platinum eligibility. Participants in the cohort updated today had been previously treated with platinum-containing chemotherapy but were checkpoint inhibitor naïve.

As of the data cut-off on July 30, 2020, 30 out of 40 patients enrolled in this checkpoint inhibitor-naïve, platinum-experienced cohort of the Phase 2 study were evaluable for response:

• Findings showed an objective response rate of 37%, with 1 patient achieving a complete response (CR) and 10 patients achieving a partial response (PR: 8 confirmed, 2 unconfirmed) in this high-risk population (based on prognostic factors and baseline disease sites)
• 22/30 (73%) patients achieved clinical benefit (combination of CR plus PR plus stable disease)
• Secondary efficacy endpoints continue to mature with a median follow-up of 8.7 months

"These data indicate that sitravatinib in combination with nivolumab resulted in a higher overall response rate, as well as longer preliminary progression free survival, when compared to what is generally seen with checkpoint inhibitors or similar tyrosine kinase inhibitor monotherapies in this setting," said Pavlos Msaouel, M.D., Ph.D., Assistant Professor, Department of Genitourinary Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas. "These data continue to show activity of the combination in this tumor setting and further demonstrate the ability of sitravatinib to augment the clinical activity of checkpoint inhibitors. We're pleased by the strength of the combination response, and as the data mature over time, we will continue to evaluate the duration of response."

The sitravatinib and nivolumab combination has been well-tolerated and consistent with what has been previously reported in urothelial carcinoma and across other tumor settings.

The primary objective of the trial is to evaluate clinical activity as measured by objective response rate. Secondary objectives include evaluation of safety, tolerability, efficacy (including duration of response, clinical benefit rate, progression free survival and overall survival), and pharmacokinetics.

About Sitravatinib

Sitravatinib is an investigational 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. Sitravatinib is being evaluated in combination with nivolumab (OPDIVO^®), an anti-PD-1 checkpoint inhibitor, in patients whose cancers have progressed despite  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 being evaluated in multiple clinical trials to treat patients who are refractory to prior immune checkpoint inhibitor therapy, including the ongoing potentially registration-enabling Phase 3 trial of sitravatinib in combinations with a checkpoint inhibitor in non-small cell lung cancer (NSCLC). In addition, sitravatinib in combinations with checkpoint inhibitors are being evaluated in selected checkpoint inhibitor naïve patients.

About Mirati Therapeutics

Mirati Therapeutics (NASDAQ: MRTX) is a San Diego-based clinical-stage biotechnology company dedicated to advancing novel therapeutics that extend the lives of patients by directly addressing the genetic and immunological drivers of cancer. Mirati is developing sitravatinib, designed to selectively target a spectrum of tyrosine kinases implicated in both tumor growth and the suppression of immune responses to tumors. Sitravatinib has demonstrated durable responses in lung cancer patients whose cancer has progressed despite treatment with checkpoint inhibitors - an area of significant unmet medical need. Sitravatinib is being evaluated in multiple clinical trials to treat patients who are refractory to prior immune checkpoint inhibitor therapy, including a potentially registration-enabling Phase 3 trial of sitravatinib in combination with a checkpoint inhibitor in non-small cell lung cancer (NSCLC) that is currently enrolling patients.

Mirati is also developing novel inhibitors of KRAS mutations including MRTX849, a potent and selective inhibitor of KRAS G12C. This historically difficult to drug target is present in approximately 14% of NSCLC adenocarcinomas, 4% of colorectal cancer as well as smaller percentages of several other difficult-to-treat cancers. MRTX849 is being evaluated in a Phase 1/2 clinical trial as a treatment for patients with KRAS G12C-positive tumors. Our research in KRAS G12C has led to breakthroughs in targeting other KRAS mutations, including G12D, which drives tumor growth in more patients than G12C and includes pancreatic, colorectal and other types of cancer. Our lead clinical candidate for KRAS G12D, MRTX1133, is in IND-enabling studies. For more information, visit www.mirati.com.

Forward Looking Statements

This press release contains forward-looking statements regarding the business of Mirati Therapeutics, Inc. ("Mirati"). Any statement describing Mirati's goals, expectations, financial or other projections, intentions or beliefs, development plans and the commercial potential of Mirati's drug development pipeline, including without limitation MRTX849, sitravatinib and MRTX1133, is a forward-looking statement and should be considered an at-risk statement. Such statements are subject to risks and uncertainties, particularly those challenges inherent in the process of discovering, developing and commercialization of new drug products that are safe and effective for use as human therapeutics, and in the endeavor of building a business around such drugs.

Mirati's forward-looking statements also involve assumptions that, if they never materialize or prove correct, could cause its results to differ materially from those expressed or implied by such forward-looking statements. Although Mirati's forward-looking statements reflect the good faith judgment of its management, these statements are based only on facts and factors currently known by Mirati. As a result, you are cautioned not to rely on these forward-looking statements. These and other risks concerning Mirati's programs are described in additional detail in Mirati's quarterly reports on Form 10-Q and annual reports on Form 10-K, which are on file with the U.S. Securities and Exchange Commission (the "SEC") available at the SEC's Internet site (www.sec.gov).These forward-looking statements are made as of the date of this press release, and Mirati assumes no obligation to update the forward-looking statements, or to update the reasons why actual results could differ from those projected in the forward-looking statements, except as required by law.

SOURCE Mirati Therapeutics, Inc.