SAN
DIEGO, May 26, 2022 /PRNewswire/ -- Mirati
Therapeutics, Inc. (NASDAQ: MRTX), a clinical-stage targeted
oncology company, today announced positive results from the
registration-enabling Phase 2 cohort of the KRYSTAL-1 study
evaluating adagrasib 600 mg BID in patients with non-small
cell lung cancer (NSCLC) harboring the
KRASG12C mutation who have received at least one
prior systemic therapy. Findings will be presented on June 3 at the 2022 American Society of Clinical
Oncology (ASCO) Annual Meeting, as an oral presentation during the
"Lung Cancer – Non-Small Cell Metastatic" session from 2:24 to 2:36 PM ET/ 1:24
to 1:36 PM CT (Abstract #9002).
Summary of Clinical Results from
Phase 2 Registration-Enabling Study
- As of October 15, 2021, 116
patients were enrolled and treated in the study. Of the patients
enrolled, 98% had prior treatment with a PD-1/L1 inhibitor
following or in combination with chemotherapy. Median follow up was
12.9 months.
- Of the patients evaluable for response (n=112), initial results
showed that the objective response rate (ORR) by Blinded
Independent Central Review (BICR) was 43%, the disease control rate
(DCR) was 80%, the median duration of response (DOR) was 8.5 months
(95% confidence interval [CI]: 6.2 – 13.8), and the median
progression-free survival (PFS) was 6.5 months (95% CI: 4.7 –
8.4).
- With a January 15, 2022 data
cutoff, the median overall survival (OS) was 12.6 months (95% CI:
9.2 – 19.2).
- The safety profile of adagrasib in this study was
consistent with prior reports and no new safety signals were
observed. The most frequent treatment related adverse events
(TRAEs) included gastrointestinal events and fatigue. The majority
of TRAEs were Grade 1–2 (53%) with Grade 3–4 TRAEs observed in 43%
of patients. Two Grade 5 TRAEs were observed. TRAEs led to
discontinuation of therapy in only 7% of patients.
"The positive and encouraging data from this trial further
support the scientific rationale for targeting the
KRASG12C mutation with adagrasib, which fully and
continually inhibits mutant KRASG12C throughout the
entire dosing period," says Alexander I.
Spira, M.D., Ph.D., FACP, Co-Director, Virginia Cancer
Specialists Research Institute. "This important dataset
demonstrates positive clinical activity with adagrasib
across molecular and clinical subgroups, including patients with
treated and stable CNS metastases."
The Company also presented results from an
exploratory, retrospective subgroup analysis from the Phase 2
NSCLC cohort of the KRYSTAL-1 study evaluating adagrasib in
patients with KRASG12C-mutated NSCLC and stable,
previously treated central nervous system (CNS) metastases (n=33).
These results showed CNS-specific activity, including a 33%
intracranial (IC) ORR by response assessment in
neuro-oncology-brain metastases (modified RANO-BM). The IC DCR was
85% (95% CI: 68 – 95).
"The exploratory, retrospective subgroup analysis of
adagrasib in patients with stable and previously treated CNS
metastases showed intracranial tumor regression," added Dr. Spira.
"These data are encouraging and contribute to the rapidly advancing
science seeking to better understand how KRASG12C
inhibitors like adagrasib can help improve patient
outcomes."
Updated Findings from Pooled
Analysis of KRYSTAL-1 NSCLC Cohorts
In addition to these results, the Company reported updated
findings from a pooled analysis in a total of 132 patients from the
KRYSTAL-1 study, including the registrational Phase 2 and Phase
1/1b NSCLC cohorts evaluating
adagrasib at a dose of 600mg BID.
As of October 15, 2021, results
from this pooled analysis showed an ORR of 44% and a disease
control rate of 81% based on central independent review. The median
DOR was 12.5 months and the median PFS was 6.9 months. With a
January 15, 2022 data cutoff, (median
duration of follow-up of 15.9 months) the median OS was 14.1
months. The safety and tolerability profile was consistent with the
above reported findings for adagrasib in patients with
advanced NSCLC. The Company plans to present full results from this
pooled analysis at a future medical congress.
"The data from the registrational lung cancer cohort of
KRYSTAL-1, including the clinical activity shown in patients with
stable, previously treated CNS metastases, further support
adagrasib's unique profile," says Charles M. Baum, M.D., Ph.D., president, founder
and head of research and development, Mirati Therapeutics, Inc.
"Mirati is at the forefront of KRAS research, and we are pleased
with the meaningfully positive clinical outcomes patients are
experiencing with adagrasib, both in previously treated lung
cancer and in other tumor settings."
On June 6, 2022, during an oral
presentation at the 2022 ASCO Annual Meeting, the Company will
present new, late-breaking results from the Phase 1b cohort of the KRYSTAL-1 study evaluating
adagrasib in active, untreated CNS metastases (Abstract
#LBA9009).
The adagrasib New Drug Application is currently being
reviewed by the U.S. Food and Drug Administration (FDA) for
Accelerated Approval (Subpart H) as a treatment for patients with
NSCLC harboring the KRASG12C mutation who have received
at least one prior systemic therapy. Adagrasib has also
received Breakthrough Therapy Designation status from the FDA for
the same indication. The Company has an ongoing confirmatory Phase
3 trial, KRYSTAL-12, evaluating adagrasib versus docetaxel
who have been previously treated for metastatic NSCLC with a
KRASG12C mutation.
Virtual Investor Event
Mirati Therapeutics will host an Investor Event on
Monday, June 6, 2022, at 8:00 PM ET/7:00 PM
CT.
Company executives will provide an overview of the
adagrasib clinical data presented at the 2022 ASCO Annual
Meeting and the Company's broader lung cancer strategy, including
in earlier lines of therapy.
Investors and the general public are invited to register and
listen to a live webcast of the event through the "Investors and
Media" section on Mirati.com. A replay of the event will be
available shortly after the conclusion of the event.
Central Nervous System (CNS)
Metastases in KRAS-Mutated Lung Cancer
The brain, along with the bone, adrenals, and liver are common
sites of extra-thoracic metastases in
NSCLC.[1]−3 CNS metastases occur
in 27−42% of patients with KRASG12C-mutated NSCLC at
diagnosis.1,4−6 Additionally, patients with CNS
metastases and KRAS-mutated NSCLC may have poor outcomes, with
median overall survival (OS) of approximately five
months.7-9
About Adagrasib
(MRTX849)
Adagrasib is an investigational, highly selective,
and potent oral small-molecule inhibitor of
KRASG12C that is optimized to sustain target
inhibition, an attribute that could be important to
treat KRASG12C-mutated cancers, as the
KRASG12C protein regenerates every 24–48
hours. Adagrasib is being evaluated as monotherapy
and in combination with other anti-cancer therapies in patients
with advanced KRASG12C-mutated solid tumors,
including NSCLC, colorectal cancer and pancreatic cancer. For more
information visit Mirati.com/science.
Mirati has an Expanded Access Program (EAP) for
investigational adagrasib for the treatment of
eligible patients with KRASG12C-mutated cancers,
regardless of tumor type, including patients with treated or
untreated CNS metastases, in the U.S. Learn more about the EAP
at Mirati.com/expanded-access-policy.
About Mirati Therapeutics,
Inc.
Mirati Therapeutics, Inc. is a clinical-stage biotechnology
company whose mission is to discover, design and deliver
breakthrough therapies to transform the lives of patients with
cancer and their loved ones. The company is relentlessly focused on
bringing forward therapies that address areas of high unmet medical
need, including lung cancer, and advancing a pipeline of novel
therapeutics targeting the genetic and immunological drivers of
cancer. Unified for patients, Mirati's vision is to unlock the
science behind the promise of a life beyond cancer. For more
information about Mirati, visit us at Mirati.com or
follow us
on Twitter, LinkedIn and Facebook.
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 adagrasib (selective
KRASG12C
inhibitor), sitravatinib (TAM receptor
inhibitor), MRTX1719 (MTA cooperative PRMT5 inhibitor), MRTX1133
(selective KRAS G12D inhibitor), and MRTX0902 (SOS1
inhibitor), 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.
References
1. Lohinai Z, Klickovits T, Moldvay J, et al. KRAS-mutation
incidence and prognostic value are metastatic site-specific in lung
adenocarcinoma: poor prognosis in patients with KRAS mutation and
bone metastasis. Sci Rep. 2017;7:39721.
2. Milovanovic IS, Stjepanovic M, Mitrovic D. Distribution
patterns of the metastases of the lung carcinoma in relation to
histological type of the primary tumor: an autopsy
study. Ann Thorac Med. 2017;12(3):191-198.
3. Wang X, Wang Z, Pan J, et al. Patterns of extrathoracic
metastases in different histological types of cancer. Front
Oncol. 2020;10:715.
4. Cui W, Franchini F, Alexander M, et al. Real world outcomes
in KRAS G12C mutation positive non-small cell lung
cancer. Lung Cancer. 2020;146:310-317.
5. Offin M, Feldman D, Ni A, et al. Frequency and outcomes of
brain metastases in patients with HER2-mutant lung cancers.
Cancer. 2019;125(24):4380-4387.
6. Tomasini P, Serdjebi C, Khobta N, et al. EGFR and KRAS
mutations predict the incidence and outcome of brain metastases in
non-small cell lung cancer. Int J Mol Sci.
2016;17(12):2132.
7. Cagney DN, Martin AM, Catalano PJ. Incidence and prognosis of
patients with brain metastases at diagnosis of systemic malignancy:
a population-based study. Neuro Oncol.
2017;19(11):1511-1521.
8. Chi A, Komaki R. Treatment of brain metastasis from lung
cancer. Cancers (Basel).
2010;2(4):2100-2137.
9. Mak KS, Gainor JF, Niemierko A, et al. Significance of
targeted therapy and genetic alterations in EGFR, ALK, or KRAS on
survival in patients with non-small cell lung cancer treated with
radiotherapy for brain metastases. Neuro Oncol.
2015;17(2):296-302.
Mirati Contacts
Investor Relations: ir@mirati.com
Media Relations: media@mirati.com
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