SAN
DIEGO, Sept. 9, 2023 /PRNewswire/ -- Mirati
Therapeutics, Inc.® (NASDAQ: MRTX), a commercial
stage research and development, biotechnology company, today
presented two-year follow-up data from a pooled analysis of the
Phase 1/1b Cohort and Phase 2 Cohort
A for the KRYSTAL-1 study evaluating adagrasib (KRAZATI®) in
patients with non-small cell lung cancer (NSCLC) harboring a
KRASG12C mutation.
In the pooled analysis, adagrasib demonstrated durable
efficacy with a median overall survival (OS) of 14.1 months and a
2-year OS rate of 31% in patients with previously treated
KRASG12C-mutated NSCLC. Exploratory analyses suggested
clinical benefit in patients with treated, stable central nervous
system (CNS) metastases at baseline with clinical benefit noted
across most baseline co-mutations.
In the study, adagrasib demonstrated a manageable
long-term safety profile with low grade treatment-related adverse
events (TRAEs). Hepatotoxicity was not observed in any patients who
received adagrasib within 30 days of prior immunotherapy
and, overall, there was a low rate of grade >3 hepatoxicity.
A confirmatory Phase 3 study, KRYSTAL-12, is ongoing, evaluating
adagrasib vs. docetaxel in previously treated patients with
KRASG12C-mutated NSCLC.
"This data reinforces the ability of adagrasib to
positively impact patients as a potential best in class option,"
said Alan Sandler, M.D., chief
medical officer, Mirati Therapeutics, Inc. "Adagrasib offers
a differentiated option for KRASG12C-mutated NSCLC as
evidenced by its clinical activity in the CNS and ability to
sequence adagrasib immediately after prior immunotherapy. We
look forward to continuing to advance adagrasib across lines of
therapy in a range of tumor types for the benefit of patients
living with KRASG12C-mutated cancer."
"These data continue to reinforce the benefit of
adagrasib for patients living with
KRASG12C-mutated NSCLC who are in need for better
options than the historical standard of care chemotherapy," Shirish
M. Gadgeel, MD, head, the Division of Hematology/Oncology,
associate director, Patient Experience and Clinical Care, the Henry
Ford Cancer Institute. "The long term overall survival for
adagrasib is meaningful for patients."
In December of 2022, adagrasib was added to the National
Comprehensive Center Network (NCCN) Guidelines for patients living
with previously treated KRASG12C-mutant NSCLC.
Following, adagrasib was added the NCCN guidelines for CNS Cancers
for patients living with previously treated
KRASG12C-mutant NSCLC and CNS metastases.
About KRAZATI® (adagrasib)
In the U.S., KRAZATI was approved by the FDA for Accelerated
Approval (Subpart H), which allows for the approval of drugs that
treat serious conditions, and that fill an unmet medical need based
on surrogate endpoints. KRAZATI was reviewed under the FDA
Real-Time Oncology Review (RTOR) pilot program, which aims to
explore a more efficient review process that ensures safe and
effective treatments are made available to patients as early as
possible. Mirati submitted a Marketing Authorization Application
(MAA) in the EU in May 2022. In 2021,
adagrasib achieved Breakthrough Therapy Designation in the U.S. as
a potential treatment for patients with NSCLC harboring the
KRASG12C mutation who have received at least one prior systemic
therapy. For Prescribing Information, visit
Mirati.com/KRAZATI_USPI.
Adagrasib continues to be 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.
KRAZATI (adagrasib) U.S. Indication
KRAZATI is indicated for the treatment of adult patients with
KRASG12C-mutated locally advanced or metastatic non-small cell lung
cancer (NSCLC), as determined by an FDA-approved test, who have
received at least one prior systemic therapy.
This indication is approved under accelerated approval based on
objective response rate (ORR) and duration of response (DOR).
Continued approval for this indication may be contingent upon
verification and description of a clinical benefit in a
confirmatory trial(s).
KRAZATI (adagrasib) Important Safety
Information
WARNINGS AND PRECAUTIONS
Gastrointestinal Adverse Reactions
- In the pooled safety population, serious gastrointestinal
adverse reactions observed were gastrointestinal obstruction in
1.6%, including 1.4% grade 3 or 4, gastrointestinal bleeding in
0.5% of patients, including 0.5% grade 3, and colitis in 0.3%,
including 0.3% grade 3. In addition, nausea, diarrhea, or vomiting
occurred in 89% of 366 patients, including 9% grade 3. Nausea,
diarrhea, or vomiting led to dosage interruption or dose reduction
in 29% of patients and permanent discontinuation of KRAZATI in
0.3%
- Monitor and manage patients using supportive care, including
antidiarrheals, antiemetics, or fluid replacement, as indicated.
Withhold, reduce the dose, or permanently discontinue KRAZATI based
on severity
QTc Interval Prolongation
- KRAZATI can cause QTc interval prolongation, which can increase
the risk for ventricular tachyarrhythmias (eg, torsades de pointes)
or sudden death
- In the pooled safety population, 6% of 366 patients with at
least one post-baseline electrocardiogram (ECG) assessment had an
average QTc ≥501 ms, and 11% of patients had an increase from
baseline of QTc >60 msec. KRAZATI causes concentration-dependent
increases in the QTc interval
- Avoid concomitant use of KRAZATI with other products with a
known potential to prolong the QTc interval. Avoid use of KRAZATI
in patients with congenital long QT syndrome and in patients with
concurrent QTc prolongation
- Monitor ECGs and electrolytes prior to starting KRAZATI, during
concomitant use, and as clinically indicated in patients with
congestive heart failure, bradyarrhythmias, electrolyte
abnormalities, and in patients who are taking medications that are
known to prolong the QT interval. Withhold, reduce the dose, or
permanently discontinue KRAZATI, depending on severity
Hepatotoxicity
- KRAZATI can cause hepatotoxicity
- In the pooled safety population, hepatotoxicity occurred in
37%, and 7% were grade 3 or 4. A total of 32% of patients who
received KRAZATI had increased alanine aminotransferase
(ALT)/increased aspartate aminotransferase (AST); 5% were grade 3
and 0.5% were grade 4. Increased ALT/AST leading to dose
interruption or reduction occurred in 11% of patients. KRAZATI was
discontinued due to increased ALT/AST in 0.5% of patients
- Monitor liver laboratory tests (AST, ALT, alkaline phosphatase,
and total bilirubin) prior to the start of KRAZATI, and monthly for
3 months or as clinically indicated, with more frequent testing in
patients who develop transaminase elevations. Reduce the dose,
withhold, or permanently discontinue KRAZATI based on severity
Interstitial Lung Disease /Pneumonitis
- KRAZATI can cause interstitial lung disease (ILD)/pneumonitis,
which can be fatal. In the pooled safety population,
ILD/pneumonitis occurred in 4.1% of patients, 1.4% were grade 3 or
4, and 1 case was fatal. The median time to first onset for
ILD/pneumonitis was 12 weeks (range: 5 to 31 weeks). KRAZATI was
discontinued due to ILD/pneumonitis in 0.8% of patients
- Monitor patients for new or worsening respiratory symptoms
indicative of ILD/pneumonitis (eg, dyspnea, cough, fever). Withhold
KRAZATI in patients with suspected ILD/pneumonitis and permanently
discontinue KRAZATI if no other potential causes of ILD/pneumonitis
are identified
Adverse Reactions
- The most common adverse reactions (≥25%) are nausea, diarrhea,
vomiting, fatigue, musculoskeletal pain, hepatotoxicity, renal
impairment, edema, dyspnea, decreased appetite
Females and Males of Reproductive Potential
- Infertility: Based on findings from animal studies, KRAZATI may
impair fertility in females and males of reproductive
potential
Please see Full Prescribing Information.
About Mirati Therapeutics, Inc.®
Mirati
Therapeutics, Inc. is a commercial stage, research and development
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 need, including lung cancer, and advancing a pipeline of
novel therapeutics targeting the genetic 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 includes
forward-looking statements regarding Mirati's business, financial
guidance and the therapeutic and commercial potential of
KRAZATI® (adagrasib), MRTX1719 (MTA-cooperative PRMT5
inhibitor), MRTX0902 (SOS1 inhibitor), and MRTX1133 (selective
KRASG12D inhibitor), Mirati's technologies and Mirati's other
products in development. Any statement describing Mirati's goals,
expectations, intentions or beliefs, financial or other
projections, is a forward-looking statement and should be
considered an at-risk statement. Such statements are subject to
certain risks and uncertainties, including those inherent in the
process of discovering, developing and commercializing medicines
that are safe and effective for use as human therapeutics, and in
the endeavor of building a business around such medicines.
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
annual report on Form 10-K, and most recent Form 10-Q, which are on
file with the Securities and Exchange Commission and 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.
Mirati Contacts
Investor Relations: ir@mirati.com
Media Relations: media@mirati.com
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