SAN DIEGO, Nov. 9, 2019 /PRNewswire/ -- Mirati
Therapeutics, Inc. (NASDAQ: MRTX), a clinical stage targeted
oncology company, today announced the presentation of initial data
from its ongoing Phase 2 clinical trial of sitravatinib in
combination with nivolumab (OPDIVO®) in metastatic
urothelial cancer (mUC) patients with documented progression on a
platinum-chemotherapy and checkpoint inhibitor. The data were
presented in an oral presentation at the Society of Immunotherapy
of Cancer (SITC) 34th Annual Meeting in National Harbor,
MD. Preliminary results from the ongoing Phase 1 study of
neoadjuvant sitravatinib combined with nivolumab in patients with
resectable squamous cell carcinoma of the oral cavity (SNOW trial)
were also presented in a poster session.
"Sitravatinib is a spectrum-selective kinase inhibitor that
potently inhibits receptor tyrosine kinases, including TAM family
receptors (TYRO3, Axl, Mer), that has the potential to increase
responsiveness in patients whose tumors are resistant to checkpoint
inhibitors. The initial efficacy data from the Phase 2 clinical
trial presented today in patients with checkpoint refractory mUC is
promising and extends the clinical benefit data beyond what has
already been demonstrated by sitravatinib combined with nivolumab
in checkpoint refractory non-small cell lung cancer (NSCLC)," said
Charles M. Baum, M.D., Ph.D.,
President and Chief Executive Officer of Mirati. "In addition, we
are evaluating sitravatinib in patients who have progressed on
checkpoint therapy, including those with NSCLC and renal cell
cancer, and we continue to expand development efforts of
sitravatinib through our collaboration with BeiGene in multiple
indications including NSCLC, renal cell cancer, hepatocellular
cancer, ovarian cancer, and gastric cancer."
The ongoing Phase 2 clinical trial, an open-label, multi-cohort
trial, is enrolling patients with advanced or metastatic urothelial
cancer who had been previously treated with a platinum-chemotherapy
and checkpoint inhibitor and had documented disease progression.
Data from Cohort 1 of the trial were presented, where patients must
have also received prior platinum-based chemotherapy. Trial
objectives included tumor regression, safety and
pharmacokinetics.
As of the data cut-off date of October
17, 2019, 22 patients were evaluable for response with at
least one radiographic scan:
- 6/22 evaluable patients achieved a confirmed Complete Response
(CR, 1 patient) or Partial Response (PR, 5 patients).
- 21/22 evaluable patients achieved a CR, PR or stable
disease.
- 4 responding patients have been treated for more than 6
months.
The combination has been well-tolerated and most adverse events
(AEs) were Grade 1 or 2.
Additionally, preliminary results from the Phase 1 SNOW trial
(sitravatinib and nivolumab in oral cavity cancer window of
opportunity study) were shown in a poster presentation. The
preliminary data suggest that the combination of neoadjuvant
sitravatinib and nivolumab is safe and active in patients with
squamous cell carcinoma of the oral cavity who are candidates for
resection. As of the data cut-off date of October 9, 2019, 9 patients had been enrolled (1
is active and 8 are in follow-up). Tumor reduction was observed in
all eight patients who were eligible for evaluation, including one
complete pathological response. All patients received postoperative
radiation therapy, and none required postoperative chemotherapy.
With a median follow-up of 31.4 weeks, all patients are alive with
no disease recurrence to date. In most patients, treatment with
sitravatinib led to a decrease in myeloid-derived suppressor cells
and a shift towards M1-type macrophages in the tumor
microenvironment, supporting previous preclinical findings.
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 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.
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's lead drug candidate,
sitravatinib, is 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 previously 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 on 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. 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, the scope, timing and
results of clinical trials, including without limitation the Phase
2 and Phase 1 clinical studies of sitravatinib in combination with
nivolumab referenced above, 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 manufacturing and
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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