Mirati Therapeutics Announces Advancement Of First-In-Class Opportunities With Sitravatinib And KRAS Inhibitor Programs
"We are very encouraged by the early results from our sitravatinib immuno-oncology program. The combination of sitravatinib and nivolumab has demonstrated durable responses and prolonged stable disease in patients with non-small cell lung cancer that have documented progression on prior checkpoint therapy. This is a patient population with poor prognosis and limited treatment options. We are focusing on accelerating this promising opportunity with sitravatinib and advancing our potentially first-in-class KRAS program, both of which address large underserved patient populations with significant market potential," said
Program updates the Company expects to provide in 2018 include:
- Phase 2 data from the immuno-oncology combination of sitravatinib and nivolumab in patients with checkpoint refractory non-small cell lung cancer (NSCLC) by mid-2018.
- Advancement of the potentially first-in-class KRAS G12C inhibitor program to an IND submission by the fourth quarter of 2018.
- Phase 1b proof-of-concept data from the study of sitravatinib as a single agent in genetically selected patients with NSCLC and other solid tumors by mid-2018.
- Phase 2 data from the immuno-oncology combination of mocetinostat and durvalumab in patients with checkpoint refractory NSCLC in the first quarter of 2018.
Mirati's Development Programs
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 tested in combination with the anti-PD-1 checkpoint inhibitor, nivolumab (OPDIVO®), in NSCLC patients who have experienced documented disease progression following treatment with a checkpoint inhibitor. The majority of NSCLC patients either do not respond to checkpoint therapy or experience disease progression following treatment. 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.
As previously reported at the IASLC 18th
Sitravatinib is also being evaluated as a single agent in a Phase 1b expansion trial enrolling patients whose tumors harbor CBL, CHR4Q12 and RET genetic alterations in NSCLC and other tumor types. In the ongoing Phase 1b study of sitravatinib as a single agent, an objective response with tumor reduction of 77% was observed in the first evaluable NSCLC patient with a CBL mutation. The Company continues to enroll patients in this trial to confirm this early promising activity and will provide a further update across all cohorts by mid-2018.
KRAS Program Advancing Towards IND in 2018
The Company has selected a clinical lead and backup compounds for advancement to IND in its potential first-in-class KRAS program. The KRAS program emerged from a joint drug discovery collaboration with
Historically, KRAS has been extremely difficult to directly inhibit due to its high affinity for GTP, and its lack of a defined binding pocket. Tumors characterized by KRAS mutations are commonly associated with poor prognosis and resistance to therapy. KRAS G12C driver mutations occur in approximately 14% of NSCLC adenocarcinoma patients and 5% of colorectal cancer patients, who have few treatment options. The Company's KRAS program has the potential to be the first direct inhibitor of this important and challenging tumor driver mutation.
Mocetinostat is a selective Class I and IV 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. The Company is conducting a Phase 2 study of mocetinostat in combination with durvalumab (IMFINZI™) in NSCLC patients who have experienced disease progression after prior treatment with checkpoint inhibitor therapy. Patients are stratified into two cohorts based upon their best response to prior checkpoint therapy. Stage 1 of the study is currently enrolling nine patients in each cohort. As previously reported, one cohort has already met the prespecified criteria for expansion into stage 2 with at least one confirmed partial response. The Company will provide an update on this trial in the first quarter of 2018.
Glesatinib has demonstrated clinical activity and acceptable tolerability in MET-altered NSCLC patients. However, in light of superior investment opportunities in its pipeline, the Company will suspend further investment in glesatinib and will pursue opportunities to partner the program. The Company intends to present glesatinib data at a future medical conference.
LSD1 Preclinical Program
The Company has elected to suspend further development of its preclinical LSD1 inhibitor program as part of its reprioritization. In light of superior investment opportunities in its pipeline, the Company will seek a partner to continue development of the program.
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 the Company that are not historical facts may be considered "forward-looking statements," including, but not limited to, 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," "would," "believe," "intend," "plan," "anticipate," "estimate," "expect," and other similar terminology. Forward-looking statements are based on current expectations of management and upon what management believes to be reasonable assumptions based on information currently available to it, and are subject to risks and uncertainties. Such risks and uncertainties may cause actual results to differ materially from the expectations set forth in the forward-looking statements. Such risks and uncertainties include, but are not limited to, potential delays in development timelines or 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
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Temre Johnson, Mirati Therapeutics Inc., Senior Manager, Investor Relations & Corporate Communications, (858) 332-3562, firstname.lastname@example.org