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)
33rd Annual Meeting in Washington, D.C. The data will be presented
today in a poster and also in an oral presentation on Sunday, November 11th.
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.
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