IMFINZI Granted Priority Review
Acceptance follows FDA’s Breakthrough Therapy
Designation
AstraZeneca and MedImmune, its global biologics research and
development arm, today announced that the US Food and Drug
Administration (FDA) has accepted a supplemental Biologics License
Application (sBLA) for IMFINZI® (durvalumab) for the
treatment of patients with locally advanced, unresectable non-small
cell lung cancer (NSCLC) whose disease has not progressed following
platinum-based chemoradiation therapy. The FDA has granted IMFINZI
Priority Review status.
The US FDA sBLA submission acceptance is an important milestone
for IMFINZI in a disease state where patients need better treatment
options and outcomes. Currently, the standard of care for these
patients with locally advanced (Stage III) lung cancer is active
monitoring following definitive chemoradiation.
The sBLA submission is based on positive progression-free
survival (PFS) data from the Phase III PACIFIC trial. The trial
continues to evaluate overall survival (OS), its other primary
endpoint. Detailed results of the PACIFIC trial, including
additional safety information, were published online in
the New England Journal of Medicine.
On September 28, 2017, the NCCN Clinical Practice Guidelines in
Oncology (NCCN Guidelines®) were updated to include durvalumab for
the treatment of patients with locally advanced, unresectable NSCLC
with no disease progression after two or more cycles of definitive
chemoradiation, based on the data from the PACIFIC Phase III trial.
This indication is not yet FDA-approved.
IMFINZI has already received accelerated approval in the US for
the treatment of patients with locally advanced or metastatic
urothelial carcinoma, who have disease progression during or
following platinum-containing chemotherapy, or whose disease has
progressed within 12 months of receiving platinum-containing
chemotherapy before (neoadjuvant) or after (adjuvant) surgery.
IMPORTANT SAFETY INFORMATION
There are no contraindications for IMFINZI® (durvalumab).
Monitor patients for clinical signs and symptoms of
immune-mediated pneumonitis, hepatitis, colitis or diarrhea,
endocrinopathies, nephritis, rash or dermatitis, other
immune-mediated adverse reactions, and infection. Please refer to
the full Prescribing Information for important dose management
information specific to adverse reactions.
Immune-Mediated Pneumonitis
In the combined safety database (n=1414), immune-mediated
pneumonitis occurred in 32 patients (2.3%), including 1 fatal case
(0.1%) and 6 Grade 3–4 cases (0.4%). In Study 1 (n=182), 1 patient
(0.5%) died from immune-mediated pneumonitis. Monitor patients for
signs and symptoms of pneumonitis and evaluate with radiographic
imaging when suspected. Administer corticosteroids for ≥Grade 2
pneumonitis. Withhold IMFINZI for Grade 2 pneumonitis; permanently
discontinue for Grade 3–4 pneumonitis.
Immune-Mediated Hepatitis
In the combined safety database (n=1414), immune-mediated
hepatitis occurred in 16 patients (1.1%), including 1 fatal case
(<0.1%) and 9 Grade 3 cases (0.6%). Grade 3–4 elevations in ALT
occurred in 40/1342 patients (3.0%), AST in 58/1336 patients
(4.3%), and total bilirubin in 37/1341 patients (2.8%). In Study 1
(n=182), 1 patient (0.5%) died from immune-mediated hepatitis, and
2 patients (1.1%) experienced immune-mediated hepatitis, including
1 Grade 3 case (0.5%). Monitor patients for abnormal liver tests in
each cycle during treatment with IMFINZI. Administer
corticosteroids and withhold IMFINZI for Grade 2–3 ALT or AST
>3–5X ULN or ≤8X ULN or total bilirubin >1.5–3X ULN or ≤5X
ULN. Permanently discontinue IMFINZI in patients with Grade 3 ALT
or AST >8X ULN or total bilirubin >5X ULN, or in patients
with concurrent ALT or AST >3X ULN and total bilirubin >2X
ULN with no other cause.
Immune-Mediated Colitis
In the combined safety database (n=1414), immune-mediated
colitis or diarrhea occurred in 18 patients (1.3%), including 1
Grade 4 case (<0.1%) and 4 Grade 3 cases (0.3%). In Study 1
(n=182), 23 patients (12.6%) experienced colitis or diarrhea,
including 2 Grade 3–4 cases (1.1%). Monitor patients for signs and
symptoms of colitis or diarrhea. Administer corticosteroids for
≥Grade 2 colitis or diarrhea. Withhold IMFINZI for Grade 2 colitis
or diarrhea; permanently discontinue for Grade 3–4 colitis or
diarrhea.
Immune-Mediated Endocrinopathies
- Immune-mediated thyroid disorders,
adrenal insufficiency, type 1 diabetes mellitus and
hypophysitis/hypopituitarism have occurred with IMFINZI. Monitor
patients for clinical signs and symptoms of endocrinopathies. For
Grade 2–4 endocrinopathies (except hypothyroidism) withhold dose
until clinically stable and offer symptomatic management for
hyperthyroidism. For Grade 2–4 hypothyroidism, initiate thyroid
hormone replacement as needed
- Thyroid disorders— In the combined
safety database (n=1414), immune-mediated hypothyroidism and
hyperthyroidism occurred in 136 patients (9.6%) and 81 patients
(5.7%), respectively. Thyroiditis occurred in 10 patients (0.7%),
including 1 Grade 3 case (<0.1%) in a patient who had a
myocardial infarction. In 9 patients with thyroiditis, transient
hyperthyroidism preceded hypothyroidism. Treatment with a
beta-blocker and/or thioamide was administered for hyperthyroidism
in five of these patients. In Study 1 (n=182), Grade 1–2
hypothyroidism or thyroiditis occurred in 10 patients (5.5%). Grade
1–2 hyperthyroidism or thyroiditis leading to hyperthyroidism
occurred in 9 patients (4.9%). Monitor patients for abnormal
thyroid function tests prior to and periodically during
treatment
- Immune-mediated adrenal
insufficiency—In the combined safety database (n=1414),
immune-mediated adrenal insufficiency occurred in 13 patients
(0.9%), including 2 Grade 3 cases (0.1%). In Study 1 (n=182), Grade
1 adrenal insufficiency occurred in 1 patient (0.5%). Administer
corticosteroids and hormone replacement as clinically
indicated
- Type 1 diabetes mellitus—In the
combined safety database (n=1414), new onset type 1 diabetes
mellitus without an alternative etiology occurred in 1 patient
(<0.1%). For type 1 diabetes mellitus, initiate insulin as
indicated and withhold IMFINZI until clinically stable
- Hypophysitis—In the combined safety
database (n=1414), hypopituitarism leading to adrenal insufficiency
and diabetes insipidus occurred in 1 patient (<0.1%). Administer
corticosteroids and hormone replacement as clinically
indicated
Other Immune-Mediated Adverse Reactions
- IMFINZI has caused immune-mediated
rash. Other immune-related adverse reactions, including aseptic
meningitis, hemolytic anemia, immune thrombocytopenic purpura,
myocarditis, myositis, nephritis, and ocular inflammatory toxicity
including uveitis and keratitis, have occurred in ≤1.0% of patients
treated with IMFINZI
- Immune-mediated rash or dermatitis—In
the combined safety database (n=1414), immune-mediated rash or
dermatitis occurred in 220 patients (15.6%) and 4 patients (0.3%)
developed vitiligo. In Study 1 (n=182), 20 patients (11.0%)
developed rash, including 1 Grade 3 case (0.5%). Patients should be
monitored for signs and symptoms of rash or dermatitis. Administer
corticosteroids if indicated. Withhold IMFINZI for Grade 3 rash or
dermatitis or Grade 2 rash or dermatitis lasting >1 week.
Permanently discontinue IMFINZI in patients with Grade 4 rash or
dermatitis
- Immune thrombocytopenic purpura—In the
combined safety database (n=1414), 1 fatal case (<0.1%) of
immune thrombocytopenic purpura occurred. Monitor patients for
signs and symptoms of immune thrombocytopenic purpura
- Nephritis—In the combined safety
database (n=1414), immune-mediated nephritis occurred in 3 patients
(0.2%), including 2 Grade 3 cases (0.1%). Monitor patients for
abnormal renal function tests prior to and during each cycle of
IMFINZI. Administer corticosteroids for ≥Grade 2 nephritis
(creatinine >1.5X ULN). Withhold IMFINZI for Grade 2 nephritis;
permanently discontinue for ≥Grade 3 nephritis (creatinine >3X
ULN)
Infection
Severe infections, including sepsis, necrotizing fasciitis, and
osteomyelitis, occurred in patients receiving IMFINZI. In the
combined safety database (n=1414), infections occurred in 531
patients (37.6%). In Study 1 (n=182), infections occurred in 54
patients (29.7%). 11 patients (6.0%) experienced Grade 3–4
infection and 5 patients (2.7%) were experiencing infection at the
time of death. 8 patients (4.4%) experienced urinary tract
infection, the most common ≥Grade 3 infection. Monitor patients for
signs and symptoms of infection and treat with anti-infectives for
suspected or confirmed infections. Withhold IMFINZI for ≥Grade 3
infection.
Infusion-Related Reactions
In the combined safety database (n=1414), severe
infusion-related reactions occurred in 26 patients (1.8%). In Study
1 (n=182), infusion-related reactions occurred in 3 patients
(1.6%). There were 5 Grade 3 (0.4%) and no Grade 4 or 5 reactions.
Patients should be monitored for signs and symptoms of
infusion-related reactions. Interrupt or slow the rate of infusion
for Grade 1–2 infusion-related reactions and permanently
discontinue for Grade 3–4 infusion-related reactions.
Embryo-Fetal Toxicity
Based on its mechanism of action and data from animal studies,
IMFINZI can cause fetal harm when administered to a pregnant woman.
There are no data on the use of IMFINZI in pregnant women. Advise
pregnant women of the potential risk to a fetus and advise women of
reproductive potential to use effective contraception during
treatment and for at least 3 months after the last dose of
IMFINZI.
Nursing Mothers
There is no information regarding the presence of IMFINZI in
human milk; however, because of the potential for adverse reactions
in breastfed infants from IMFINZI, advise a lactating woman not to
breastfeed during treatment and for at least 3 months after the
last dose.
Most Common Adverse Reactions
- The most common adverse reactions
(≥15%) were fatigue (39%), musculoskeletal pain (24%), constipation
(21%), decreased appetite (19%), nausea (16%), peripheral edema
(15%), and urinary tract infection (15%). The most common Grade 3
or 4 adverse reactions (≥3%) were fatigue, urinary tract infection,
musculoskeletal pain, abdominal pain, dehydration, and general
physical health deterioration
- Adverse reactions leading to
discontinuation of IMFINZI occurred in 3.3% of patients. Serious
adverse reactions occurred in 46% of patients. The most frequent
serious adverse reactions (>2%) were acute kidney injury (4.9%),
urinary tract infection (4.4%), musculoskeletal pain (4.4%), liver
injury (3.3%), general physical health deterioration (3.3%),
sepsis, abdominal pain, and pyrexia/tumor associated fever (2.7%
each)
The safety and effectiveness of IMFINZI have not been
established in pediatric patients.
Please see complete Prescribing Information
including Patient Information.
NOTES TO EDITORS
About Locally Advanced (Stage III) NSCLC
Locally advanced (Stage III) lung cancer is divided into three
sub-categories (IIIA, IIIB and IIIC), which are defined by how much
the cancer has spread locally and the possibility of surgery. This
differentiates it from Stage IV disease, when the cancer has spread
(metastasized) to distant organs.
Approximately one in four patients with non-small cell lung
cancer present with locally advanced (Stage III) disease, which is
estimated to affect over 43,000 patients annually in the United
States. About half of these patients have tumors that are
unresectable. The current standard of care is chemotherapy and
radiation followed by active surveillance to monitor for
progression. The prognosis remains poor and long-term survival
rates are low.
About PACIFIC
The PACIFIC trial is a randomized, double-blind,
placebo-controlled, multi-center trial of durvalumab as sequential
treatment in unselected patients with locally advanced,
unresectable (Stage III) non-small cell lung cancer who have not
progressed following platinum-based chemotherapy concurrent with
radiation therapy.
The trial involved 235 centers across 26 countries, including
approximately 700 patients. The primary endpoints of the trial are
progression-free survival (PFS) and overall survival (OS), and
secondary endpoints include landmark PFS and OS, objective response
rate, duration of response and time to death or distant
metastases.
About IMFINZI® (durvalumab)
IMFINZI® (durvalumab) is a human monoclonal antibody directed
against PD-L1, which blocks the interaction of PD-L1 with PD-1 and
CD80.
IMFINZI has already received accelerated approval in the US for
the treatment of patients with locally advanced or metastatic
urothelial carcinoma, who have disease progression during or
following platinum-containing chemotherapy, or whose disease has
progressed within 12 months of receiving platinum-containing
chemotherapy before (neoadjuvant) or after (adjuvant) surgery. This
indication is approved under accelerated approval based on tumor
response rate and duration of response. Continued approval for this
indication may be contingent upon verification and description of
clinical benefit in confirmatory trials.
As part of a broad development program, durvalumab is also being
investigated for the adjuvant treatment of patients with NSCLC in
the CCTG (Canadian Cancer Trials Group) trial ADJUVANT (BR31). In
the MYSTIC, NEPTUNE, and PEARL Phase III trials, durvalumab is
being studied for 1st-line treatment as monotherapy and/or in
combination with tremelimumab, an anti-CTLA-4 monoclonal antibody,
for the treatment of metastatic NSCLC. The POSEIDON trial is
investigating durvalumab with and without tremelimumab in
combination with chemotherapy in the same population.
About AstraZeneca in Lung Cancer
AstraZeneca is committed to developing therapies to help every
patient with lung cancer. We have two approved therapies and a
growing pipeline that targets genetic changes in tumor cells and
boosts the power of the immune response against cancer. Our
unrelenting pursuit of science aims to deliver more breakthrough
therapies with the goal of extending and improving the lives of
patients across all stages of disease and lines of therapy.
About AstraZeneca’s Approach to Immuno-Oncology
Immuno-Oncology (IO) is a therapeutic approach designed to
stimulate the body’s immune system to attack tumors. At AstraZeneca
and MedImmune, our biologics research and development arm, our IO
portfolio is anchored by immunotherapies that have been designed to
overcome anti-tumor immune suppression. We believe that IO-based
therapies will offer the potential for life-changing cancer
treatments for the vast majority of patients.
We are pursuing a comprehensive clinical trial program that
includes durvalumab (anti-PD-L1 antibody) monotherapy and in
combination with tremelimumab (anti-CTLA-4 antibody) in multiple
tumor types, stages of disease, and lines of therapy, using the
PD-L1 biomarker as a decision-making tool to define the best
potential treatment path for a patient. In addition, the ability to
combine our IO portfolio with small, targeted molecules from across
our oncology pipeline, and with those of our research partners, may
provide new treatment options across a broad range of tumors.
About AstraZeneca in Oncology
AstraZeneca has a deep-rooted heritage in Oncology and offers a
quickly growing portfolio of new medicines that has the potential
to transform patients’ lives and the Company’s future. With at
least six new medicines to be launched between 2014 and 2020, and a
broad pipeline of small molecules and biologics in development, we
are committed to advance New Oncology as one of AstraZeneca’s five
Growth Platforms focused on lung, ovarian, breast and blood
cancers. In addition to our core capabilities, we actively pursue
innovative partnerships and investments that accelerate the
delivery of our strategy as illustrated by our investment in Acerta
Pharma in hematology.
By harnessing the power of four scientific platforms –
Immuno-Oncology, Tumor Drivers and Resistance, DNA Damage Response
and Antibody Drug Conjugates – and by championing the development
of personalized combinations, AstraZeneca has the vision to
redefine cancer treatment and one day eliminate cancer as a cause
of death.
About MedImmune
MedImmune is the global biologics research and development arm
of AstraZeneca, a global, innovation-driven biopharmaceutical
business that focuses on the discovery, development and
commercialization of small molecule and biologic prescription
medicines. MedImmune is pioneering innovative research and
exploring novel pathways across Oncology; Respiratory,
Cardiovascular & Metabolic Diseases; and Infection and
Vaccines. The MedImmune headquarters is located in Gaithersburg,
MD, one of AstraZeneca’s three global R&D centers, with
additional sites in Cambridge, UK, and Mountain View, CA. For more
information, please visit www.medimmune.com.
About AstraZeneca
AstraZeneca is a global, science-led biopharmaceutical company
that focuses on the discovery, development and commercialization of
prescription medicines, primarily for the treatment of diseases in
three main therapy areas – Oncology, Cardiovascular & Metabolic
Diseases and Respiratory. The Company also is selectively active in
the areas of autoimmunity, neuroscience and infection. AstraZeneca
operates in over 100 countries and its innovative medicines are
used by millions of patients worldwide. For more information,
please visit www.astrazeneca-us.com and follow us on Twitter
@AstraZenecaUS.
US-15091 Last Updated 10/17
View source
version on businesswire.com: http://www.businesswire.com/news/home/20171017005357/en/
AstraZenecaMichele Meixell, +1 302-885-2677Stephanie Wiswall, +1
302-885-2677
AstraZeneca (NYSE:AZN)
Historical Stock Chart
From Aug 2024 to Sep 2024
AstraZeneca (NYSE:AZN)
Historical Stock Chart
From Sep 2023 to Sep 2024