-
Approval provides first
targeted treatment in the US specifically for BRAF V600E
mutation-positive metastatic NSCLC
-
More than 60% of
treatment-naïve and previously treated patients with BRAF V600E
mutant metastatic NSCLC responded to Tafinlar + Mekinist in a
pivotal study[1]
-
BRAF V600E is an aggressive
mutation that may be associated with a poorer prognosis in patients
with NSCLC[2]
Basel, June 22, 2017
- Novartis today announced the US Food and
Drug Administration (FDA) approval of Tafinlar®
(dabrafenib) in combination with Mekinist® (trametinib)
to treat patients with metastatic non-small cell lung cancer
(NSCLC) whose tumors express the BRAF V600E mutation. The FDA
granted Tafinlar + Mekinist Breakthrough Therapy designation in
July 2015 for the treatment of patients with advanced or metastatic
BRAF V600E mutation-positive NSCLC who received previous treatment
with chemotherapy.
"Patients with BRAF V600E mutation-positive
metastatic NSCLC have responded less favorably to standard
chemotherapy, suggesting that there is a critical need for a
targeted therapy," said Bruno Strigini, CEO, Novartis Oncology.
"Today's approval of the Tafinlar + Mekinist combination validates
our expertise in tumor biology, which enabled us to develop the
first targeted treatment for people with this rare mutation."
"The approval of Tafinlar + Mekinist makes BRAF V600E the fourth
actionable genomic biomarker in metastatic NSCLC - along
with EGFR, ALK and ROS-1," said Bruce Johnson, MD, Professor of
Medicine, Chief Clinical Research Officer, Dana-Farber Cancer
Institute and Harvard Medical School at Dana-Farber Cancer
Institute. "This is an important milestone for the lung cancer
community as we are continuing to better understand the genomic
drivers of cancer and develop effective treatments
targeted for these biomarkers."
The FDA approval is based on safety and efficacy of Tafinlar in
combination with Mekinist in a Phase II, three-cohort, multicenter,
non-randomized, non-comparative and open-label study in which
patients with stage IV BRAF V600E mutant NSCLC were enrolled (36
treatment-naïve [previously untreated] and 57 previously treated
with chemotherapy)[1].
Among the 36 treatment-naïve patients receiving 150 mg of Tafinlar
twice daily and 2 mg of Mekinist once daily, the overall response
rate (ORR) was 61% (95% confidence interval [CI]: 44%, 77%)[1]. In
the previously treated population receiving the same dosage,
patients demonstrated an ORR of 63% (95% CI: 49%, 76%)[1]. The ORR
was assessed by independent review committee. The median duration
of response in the treatment naïve cohort was not estimable (95%
CI: 6.9, not estimable) and in the previously treated patient
cohort was 12.6 months (95% CI: 5.8, not estimable)[1]. An in-depth
analysis of data from the treatment-naïve cohort will be presented
at an upcoming medical meeting.
The most common adverse events (incidence >20%)
were pyrexia, fatigue, nausea, vomiting, diarrhea, dry skin,
decreased appetite, edema, rash, chills, hemorrhage, cough and
dyspnea.
BRAF mutations appear in approximately 1-3% of
NSCLC cases worldwide[3]. There is an urgency to treat people with
this mutation, as BRAF V600E mutation-positive tumors have been
shown to be more aggressive and may lead to a poorer
prognosis[2].
The treatment combination was approved with Thermo
Fisher Scientific's Oncomine(TM) Dx Target Test to identify a BRAF
V600E mutation in eligible patients. This qualitative in vitro
diagnostic test uses targeted high throughput, parallel-sequencing
technology to detect sequence variations in select genes, including
BRAF V600E, in DNA and RNA isolated from formalin-fixed,
paraffin-embedded tumor (FFPE) tissue samples from patients with
non-small cell lung cancer (NSCLC) using the Ion PGM(TM) Dx
System.
Tafinlar + Mekinist was approved by the European
Commission (EC) in March 2017 for the treatment of patients with
BRAF V600 advanced mutation-positive NSCLC.
Novartis Commitment to Lung
Cancer
Worldwide, lung cancer causes more deaths than colon, breast and
prostate cancer combined, and an estimated 1.8 million new cases of
lung cancer are diagnosed each year[4],[5]. Among patients with
NSCLC, roughly 30% have an actionable mutation that may be targeted
with available therapies[6]-[9]. To determine the most appropriate
treatment, medical organizations recommend genomic testing for
patients with lung cancer[10].
Novartis Oncology's research in targeted therapies
has helped transform treatment approaches for patients living with
mutation-driven types of lung cancer. Patients with mutation-driven
NSCLC may be candidates for treatment with targeted
therapies[6].
Novartis continues its commitment to the global
lung cancer community through ongoing studies, as well as the
exploration of investigational compounds that target genetic
biomarkers in NSCLC.
About Tafinlar + Mekinist
Combination
Combination use of Tafinlar + Mekinist in patients with
unresectable or metastatic melanoma who have a BRAF V600E mutation
is approved in the US, EU, Australia, Canada, and additional
countries. The combination of Tafinlar and Mekinist is also
approved for the treatment of advanced non-small cell lung cancer
with a BRAF V600 mutation in Europe.
Tafinlar and Mekinist target different kinases
within the serine/threonine kinase family - BRAF and MEK1/2,
respectively - in the RAS/RAF/MEK/ERK pathway, which is implicated
in non-small cell lung cancer (NSCLC) and melanoma, among other
cancers. When Tafinlar is used with Mekinist, the combination has
been shown to slow tumor growth more than either drug alone. The
combination of Tafinlar + Mekinist is currently being investigated
in an ongoing clinical trial program across a range of tumor types
conducted in study centers worldwide.
The safety and efficacy profile of the Tafinlar +
Mekinist combination has not yet been established outside of the
approved indications.
Tafinlar and Mekinist are also indicated in more
than 50 countries worldwide, including the US and EU, as single
agents to treat patients with unresectable or metastatic melanoma
with a BRAF V600E mutation.
INDICATIONS
TAFINLAR, in combination with MEKINIST, is a prescription medicine
used to treat people with a type of skin cancer called melanoma
that has spread to other parts of the body or cannot be removed by
surgery, and that has a certain type of abnormal "BRAF" gene.
MEKINIST should not be used to treat people who
already have received a BRAF inhibitor for treatment of their
melanoma, and it did not work or is no longer working.
TAFINLAR, in combination with MEKINIST, is a prescription
medication used to treat a type of lung cancer called non-small
cell lung cancer (NSCLC) that has spread to other parts of the body
(metastatic NSCLC), and that has a certain type of abnormal "BRAF
V600E" gene.
IMPORTANT SAFETY INFORMATION for
TAFINLAR® (dabrafenib) capsules and MEKINIST®
(trametinib) tablets
TAFINLAR, in combination with MEKINIST, may cause serious side
effects such as the risk of new cancers, including a type of skin
cancer called cutaneous squamous cell carcinoma (cuSCC) and a type
of skin cancer called basal cell carcinoma. Patients should be
advised to contact their doctor immediately for a new wart, skin
sore, or bump that bleeds or does not heal, or a change in the size
or color of a mole.
TAFINLAR, in combination with MEKINIST, can cause serious bleeding
problems, especially in the brain or stomach, and can lead to
death. Patients should be advised to call their health care
provider and get medical help right away if they have headaches,
dizziness, or feel weak, cough up blood or blood clots, vomit blood
or their vomit looks like "coffee grounds," or have red or black
stools that look like tar.
TAFINLAR, in combination with MEKINIST, can cause
inflammation of the intestines, or tears in the stomach or
intestines that can lead to death. Patients should tell their
health care provider immediately if they have any of the following
symptoms: bleeding (see bleeding problems below); diarrhea (loose
stools) or more bowel movements than usual, stomach-area (abdomen)
pain or tenderness; fever, and nausea.
TAFINLAR, in combination with MEKINIST, can cause
blood clots in the arms or legs, which can travel to the lungs and
can lead to death. Patients should be advised to get medical help
right away if they have the following symptoms: chest pain, sudden
shortness of breath or trouble breathing, pain in their legs with
or without swelling, swelling in their arms or legs, or a cool or
pale arm or leg.
TAFINLAR, in combination with MEKINIST, can cause
heart problems, including heart failure. A patient's heart function
should be checked before and during treatment. Patients should be
advised to call their health care provider right away if they have
any of the following signs and symptoms of a heart problem: feeling
like their heart is pounding or racing, shortness of breath,
swelling of their ankles and feet, or feeling lightheaded.
TAFINLAR, in combination with MEKINIST, can cause
severe eye problems that can lead to blindness. Patients should be
advised to call their health care provider right away if they get:
blurred vision, loss of vision, or other vision changes, seeing
color dots, halo (seeing blurred outline around objects), eye pain,
swelling, or redness.
TAFINLAR, in combination with MEKINIST, can cause
lung or breathing problems. Patients should be advised to tell
their health care provider if they have new or worsening symptoms
of lung or breathing problems, including shortness of breath or
cough.
Fever is common during treatment with TAFINLAR in
combination with MEKINIST, but may also be more serious. Fever may
happen often or may be severe. In some cases, chills or shaking
chills, too much fluid loss (dehydration), low blood pressure,
dizziness, or kidney problems may happen with the fever. Patients
should be advised to call their health care provider right away if
they get a fever.
Rash and other skin reactions are common serious
side effects of TAFINLAR, in combination with MEKINIST. In some
cases these rashes and other skin reactions can be severe or
serious and may need to be treated in a hospital. Patients should
be advised to call their health care provider if they get any of
the following symptoms: skin rash that bothers them or does not go
away, acne, redness, swelling, peeling, or tenderness of hands or
feet, or skin redness.
Some people may develop high blood sugar or
worsening diabetes during treatment with TAFINLAR, in combination
with MEKINIST. For patients who are diabetic, their health care
provider should check their blood sugar levels closely during
treatment. Their diabetes medicine may need to be changed. Patients
should be advised to tell their health care provider if they have
increased thirst, urinate more often than normal, or produce an
increased amount of urine.
TAFINLAR, in combination with MEKINIST, may cause
healthy red blood cells to break down too early in people with G6PD
deficiency. This may lead to a type of anemia called hemolytic
anemia, where the body does not have enough healthy red blood
cells. Patients should be advised to tell their health care
provider if they have yellow skin (jaundice), weakness or
dizziness, or shortness of breath.
TAFINLAR, in combination with MEKINIST, can cause
new or worsening high blood pressure (hypertension). A patient's
blood pressure should be checked during treatment. Patients should
be advised to tell their health care provider if they develop high
blood pressure, their blood pressure worsens, or if they have
severe headache, lightheadedness, or dizziness.
Common side effects of TAFINLAR, in combination
with MEKINIST, in people with melanoma include: fever, nausea,
chills, headache, joint aches, cough, diarrhea, rash, vomiting,
high blood pressure (hypertension), and swelling of the face, arms,
or legs.
Common side effects of TAFINLAR, in combination
with MEKINIST, in people with NSCLC include: fever, fatigue,
nausea, vomiting, diarrhea, dry skin, decreased appetite, rash,
swelling of the face, arms and legs, diarrhea, chills, bleeding,
cough, and shortness of breath.
Please see full prescribing
information for TAFINLAR and MEKINIST at https://www.hcp.novartis.com/products/tafinlar-mekinist/.
Disclaimer
The foregoing release contains forward-looking statements that can
be identified by words such as "may," "Breakthrough Therapy
designation," "suggesting," "continuing," "will," "upcoming,"
"commitment," "recommend," "continues," "ongoing," "exploration,"
"investigational," "being investigated," "yet," "contingent," or
similar terms, or by express or implied discussions regarding
potential new indications or labeling for Tafinlar + Mekinist, or
regarding potential future revenues from Tafinlar and Mekinist,
both as single agents and in combination with the other. You should
not place undue reliance on these statements. Such forward-looking
statements are based on the current beliefs and expectations of
management regarding future events, and are subject to significant
known and unknown risks and uncertainties. Should one or more of
these risks or uncertainties materialize, or should underlying
assumptions prove incorrect, actual results may vary materially
from those set forth in the forward-looking statements. There can
be no guarantee that Tafinlar + Mekinist will be submitted or
approved for any additional indications or labeling in any market,
or at any particular time. Nor can there be any guarantee that
Tafinlar and Mekinist, either as single agents or in combination
with the other will be commercially successful in the future. In
particular, management's expectations regarding Tafinlar and
Mekinist, both as single agents and in combination with the other
could be affected by, among other things, the uncertainties
inherent in research and development, including clinical trial
results and additional analysis of existing clinical data;
regulatory actions or delays or government regulation generally;
the company's ability to obtain or maintain proprietary
intellectual property protection; general economic and industry
conditions; global trends toward health care cost containment,
including ongoing pricing and reimbursement pressures; safety,
quality or manufacturing issues, and other risks and factors
referred to in Novartis AG's current Form 20-F on file with the US
Securities and Exchange Commission. Novartis is providing the
information in this press release as of this date and does not
undertake any obligation to update any forward-looking statements
contained in this press release as a result of new information,
future events or otherwise.
About Novartis
Novartis provides innovative healthcare solutions that address the
evolving needs of patients and societies. Headquartered in Basel,
Switzerland, Novartis offers a diversified portfolio to best meet
these needs: innovative medicines, cost-saving generic and
biosimilar pharmaceuticals and eye care. Novartis has leading
positions globally in each of these areas. In 2016, the Group
achieved net sales of USD 48.5 billion, while R&D throughout
the Group amounted to approximately USD 9.0 billion. Novartis Group
companies employ approximately 118,000 full-time-equivalent
associates. Novartis products are sold in approximately 155
countries around the world. For more information, please visit
http://www.novartis.com.
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Oncomine(TM) Dx Target Test and Ion PGM(TM) Dx
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References
[1] Tafinlar + Mekinist Important Safety Information.
[2] Marchetti A, Felicioni L, Malatesta S, et al. Clinical Features
and Outcome of Patients with Non-Small-Cell Lung Cancer Harboring
BRAF Mutations. J Clin Oncol. 2011; 29:26, 3574-3579.
[3] Chen D, Zhang L, Huang J, et al. BRAF Mutations in Patients
with Non-Small Cell Lung Cancer: A Systematic Review and
Meta-Analysis. PLOS One. 2014; 9:6,
1-7.
[4] World Health Organization. Estimated number of deaths, both
sexes, worldwide in 2012. World Health Organization.
http://gco.iarc.fr/today/online-analysis-pie?mode=cancer&mode_population=continents&population=900&sex=0&cancer=11&type=1&statistic=0&prevalence=0&color_palette=default.
Accessed January 2017.
[5] World Health Organization. International Agency for Research on
Cancer. GLOBOCAN 2012: Estimated Cancer Incidence, Mortality and
Prevalence Worldwide in 2012. Lung Cancer. Available at
http://globocan.iarc.fr/Pages/fact_sheets_cancer.aspx?cancer=lung.
Accessed February 2017.
[6] Riess JW, Wakelee, HA. Metastatic Non-Small Cell Lung Cancer
Management: Novel Targets and Recent Clinical Advances. Clinical
Advances in Hematology & Oncology. 2012; 10: 226-224.
[7] Pao W, Girard N. New driver mutations in non-small-cell lung
cancer. Lancet Oncol. 2011;12:175-180.
[8] Paik PK, Arcila ME, Fara M, et al. Clinical Characteristics of
Patients With Lung Adenocarcinomas Harboring BRAF Mutations. J Clin
Oncol. 2011;29:2046-2051.
[9] Takeuchi, K, Soda M, Togashi Y, et al. RET, ROS1 and ALK
fusions in lung cancer. Nature. 2012;378-381.
[10] Lindeman, N.I., et al. Molecular Testing Guideline for
Selection of Lung Cancer Patients for EGFR and ALK Tyrosine Kinase
Inhibitors. Arch Pathol Lab Med. 2013; 137: 828-1174.
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