Mirati Therapeutics Presents Updated Positive Clinical Data From Sitravatinib Immuno-Oncology Combination Trial At ESMO 2018 Congress And Announces FDA Guidance For Registration Trial

- Updated analysis from ongoing Phase 2 trial of sitravatinib in combination with nivolumab demonstrated significant clinical activity in patients with checkpoint refractory non-small cell lung cancer (NSCLC)

- 16 partial or complete responses observed in first 56 evaluable patients

- Tumor regressions in 45/56 evaluable patients

- Successful end of phase 2 FDA meeting provides guidance for registration study in second line NSCLC with a path to potential accelerated U.S. approval

- Company to host conference call and webcast on Monday, October 22nd at 2:00 p.m. CEST/8:00 a.m. EDT/5:00 a.m. PDT

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Mirati Therapeutics, Inc.

Oct 22, 2018, 06:10 ET

SAN DIEGO, Oct. 22, 2018 /PRNewswire/ -- Mirati Therapeutics, Inc. (NASDAQ: MRTX), a clinical stage targeted oncology company, today announced the presentation of updated data from its ongoing Phase 2 clinical trial of sitravatinib in combination with OPDIVO^® (nivolumab) in non-small cell lung cancer (NSCLC) patients with documented progression on prior immune checkpoint inhibitor therapy. The data were presented today in a Proffered Paper Session (oral presentation) at the European Society for Medical Oncology (ESMO) 2018 Congress in Munich, Germany.

Highlights from the Proffered Paper Sessions (Oral Presentations) at ESMO 2018

An ongoing Phase 2 study is evaluating the efficacy and safety of sitravatinib in combination with OPDIVO^® (nivolumab), an anti-PD-1 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 cutoff date of August 27, 2018:

56 patients were evaluable for response with at least one radiographic scan. Patients had a median of two lines of previous therapy.
45/56 of evaluable patients demonstrated tumor reductions.
18/56 of evaluable patients demonstrated tumor reductions of greater than 30%.
16/56 of evaluable patients achieved a Partial Response (PR) or Complete Response (CR).

9 confirmed PRs or CRs.
2 unconfirmed PRs or CRs that remain on trial awaiting confirmation.
5 unconfirmed PRs or CRs that will not be confirmed.

26/56 evaluable patients remained on treatment at the time of data cut-off including 8 responding patients.
A preliminary Kaplan-Meier estimate of median duration of response was greater than 9 months.

6 responding patients have been treated for more than 6 months.
2 responding patients have been treated for more than 12 months.

The combination has been well-tolerated and most adverse events (AEs) were Grade 1 or 2.

"To date, the combination of sitravatinib and nivolumab has demonstrated a significant number of durable responses in patients with advanced NSCLC who experienced disease progression following prior checkpoint inhibitor therapy, which is one of the most challenging clinical scenarios that we currently face for this patient population," said Ticiana Leal, M.D., Assistant Professor of Medicine, Thoracic Oncology Program Leader at the University of Wisconsin. "The results of the study are encouraging as it continues to show a clinical benefit for these patients and has a favorable safety profile."

Sitravatinib Registration Plans

The Company also provided an update on the regulatory pathway for sitravatinib in checkpoint refractory NSCLC patients following a successful end of phase 2 meeting with the U.S. Food and Drug Administration (FDA). Based on guidance received from the FDA, Mirati plans to initiate a Phase 3 randomized clinical trial in second line patients comparing the combination of sitravatinib plus a checkpoint inhibitor to docetaxel in patients whose tumors have progressed on prior checkpoint inhibitor therapy.

The trial will include an interim analysis of overall response rate (ORR) as a surrogate endpoint to serve as the basis for potential Subpart H accelerated approval. This interim analysis and the use of a docetaxel control arm follows clear guidance from the FDA.
The primary endpoint of the final analysis for the Phase 3 clinical trial will be overall survival.
The trial will enroll patients with NSCLC whose tumors have progressed following treatment with a checkpoint inhibitor and platinum-based chemotherapy.
Patients will be randomized for treatment with either the combination of sitravatinib with a checkpoint inhibitor or single-agent docetaxel.
The Company plans to initiate the pivotal Phase 3 in the first half of 2019. Ultimately, the Company expects this trial to enable a new drug application (NDA) for the treatment of NSCLC patients whose tumors have progressed following treatment with a platinum containing regimen and a checkpoint inhibitor.

"There are limited treatment options for NSCLC patients whose tumors progress following checkpoint inhibitor therapy," said Charles M. Baum, M.D., Ph.D., President and Chief Executive Officer, Mirati Therapeutics, Inc. "Based on the data from our ongoing Phase 2 clinical trial we believe that the planned Phase 3 clinical trial will demonstrate a greater response rate and overall survival compared with the historical clinical outcomes for late stage NSCLC patients treated with single-agent docetaxel, where response rates range from 7-11%. The combination of sitravatinib and nivolumab has continued to show it is well tolerated with manageable side effects. We remain encouraged by the frequency and duration of the responses observed to date in this patient population with limited treatment options where responses would not be expected from re-treatment with a checkpoint inhibitor alone."

Investor Call and Webcast Information

After the oral presentation, Mirati will host a live conference call and webcast, led by Dr. Charles Baum, on Monday, October 22, 2018, at 2:00 p.m. CEST/8:00 a.m. EDT/5:00 a.m. PDT. The live call can be accessed by dialing (866) 324-3683 (toll free) or (509) 844-0959 (international) and then using passcode 3890724. A telephone replay will be made available by dialing (855) 859-2056 (toll free) or (404) 537-3406 (international) using conference replay ID 3890724.

The call will also be webcast live through the "Investors" section of the Mirati corporate website at http://ir.mirati.com/events-and-presentations. A replay of the webcast will be available on the Mirati website shortly after the conclusion of the event.

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 enrolling patients whose tumors harbor specific mutations in the CBL kinase. 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 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.