Decision based on NIAGARA Phase III trial
results which demonstrated a statistically significant and
clinically meaningful event-free and overall survival
benefit
If approved, this will be the first and only
perioperative immunotherapy regimen in this curative-intent
setting
AstraZeneca’s supplemental Biologics License Application (sBLA)
for IMFINZI® (durvalumab) has been accepted and granted Priority
Review in the US for the treatment of patients with muscle-invasive
bladder cancer (MIBC).
The Food and Drug Administration (FDA) grants Priority Review to
applications for medicines that, if approved, would offer
significant improvements over available options by demonstrating
safety or efficacy improvements, preventing serious conditions or
enhancing patient compliance.1 The Prescription Drug User Fee Act
date, the FDA action date for their regulatory decision, is
anticipated during the second quarter of 2025.
Approximately one in four patients with bladder cancer has
evidence of the tumor invading the muscle wall of the bladder
(without distant metastases), known as MIBC.2,3 In MIBC, a
curative-intent setting, approximately 117,000 patients are treated
with current standard of care.4 Standard treatment includes
neoadjuvant chemotherapy and radical cystectomy. However, even
after cystectomy, patients experience high rates of disease
recurrence and a poor prognosis.5
Susan Galbraith, Executive Vice President, Oncology R&D,
AstraZeneca, said: “New options for muscle-invasive bladder cancer
are vital because nearly half of patients will see their cancer
return or progress despite undergoing curative-intent treatment,
including removal of their bladder. Today’s Priority Review
designation recognizes the urgent need for new options for these
patients and the potential of IMFINZI to transform the standard of
care as the first and only perioperative immunotherapy regimen to
delay recurrence and extend survival in this setting.”
The sBLA is based on data from the NIAGARA Phase III trial which
was presented during a Presidential Symposium at the 2024 European
Society for Medical Oncology (ESMO) Congress and simultaneously
published in The New England Journal of Medicine.
In the trial, patients were treated with IMFINZI in combination
with neoadjuvant chemotherapy before radical cystectomy followed by
IMFINZI as adjuvant monotherapy, or neoadjuvant chemotherapy before
radical cystectomy. In a planned interim analysis, perioperative
IMFINZI demonstrated a 32% reduction in the risk of disease
progression, recurrence, not undergoing surgery, or death versus
neoadjuvant chemotherapy with radical cystectomy alone (based on
event-free survival [EFS] hazard ratio [HR] of 0.68; 95% confidence
interval [CI] 0.56-0.82; p<0.0001). Estimated median EFS was not
yet reached for the IMFINZI arm versus 46.1 months for the
comparator arm. An estimated 67.8% of patients treated with the
IMFINZI regimen were event free at two years compared to 59.8% in
the comparator arm.
Results from the key secondary endpoint of overall survival (OS)
showed that the IMFINZI perioperative regimen reduced the risk of
death by 25% versus neoadjuvant chemotherapy with radical
cystectomy (based on OS HR of 0.75; 95% CI 0.59-0.93; P=0.0106).
Median survival was not yet reached for either arm. An estimated
82.2% of patients treated with the IMFINZI regimen were alive at
two years compared to 75.2% in the comparator arm.
IMFINZI was generally well tolerated, and no new safety signals
were observed in the neoadjuvant and adjuvant settings. Further,
IMFINZI neoadjuvant chemotherapy was consistent with the known
profiles of the individual agents and did not impact patients’
ability to complete four cycles of chemotherapy or undergo surgery
compared to neoadjuvant chemotherapy alone.
Regulatory applications are currently under review in the EU,
Japan and several other countries based on the NIAGARA results.
IMPORTANT SAFETY INFORMATION
There are no contraindications for IMFINZI® (durvalumab) or
IMJUDO® (tremelimumab-actl).
Severe and Fatal Immune-Mediated Adverse Reactions
Important immune-mediated adverse reactions listed under Warnings
and Precautions may not include all possible severe and fatal
immune-mediated reactions. Immune-mediated adverse reactions, which
may be severe or fatal, can occur in any organ system or tissue.
Immune-mediated adverse reactions can occur at any time after
starting treatment or after discontinuation. Monitor patients
closely for symptoms and signs that may be clinical manifestations
of underlying immune-mediated adverse reactions. Evaluate clinical
chemistries including liver enzymes, creatinine,
adrenocorticotropic hormone (ACTH) level, and thyroid function at
baseline and before each dose. In cases of suspected
immune-mediated adverse reactions, initiate appropriate workup to
exclude alternative etiologies, including infection. Institute
medical management promptly, including specialty consultation as
appropriate. Withhold or permanently discontinue IMFINZI and IMJUDO
depending on severity. See USPI Dosing and Administration for
specific details. In general, if IMFINZI and IMJUDO requires
interruption or discontinuation, administer systemic corticosteroid
therapy (1 mg to 2 mg/kg/day prednisone or equivalent) until
improvement to Grade 1 or less. Upon improvement to Grade 1 or
less, initiate corticosteroid taper and continue to taper over at
least 1 month. Consider administration of other systemic
immunosuppressants in patients whose immune-mediated adverse
reactions are not controlled with corticosteroid therapy.
Immune-Mediated Pneumonitis
IMFINZI and IMJUDO can cause immune-mediated pneumonitis, which may
be fatal. The incidence of pneumonitis is higher in patients who
have received prior thoracic radiation.
- IMFINZI as a Single Agent
- In patients who did not receive recent prior radiation, the
incidence of immune-mediated pneumonitis was 2.4% (34/1414),
including fatal (<0.1%), and Grade 3-4 (0.4%) adverse
reactions.
- In patients who received recent prior radiation, the incidence
of pneumonitis (including radiation pneumonitis) in patients with
unresectable Stage III NSCLC following definitive chemoradiation
within 42 days prior to initiation of IMFINZI in PACIFIC was 18.3%
(87/475) in patients receiving IMFINZI and 12.8% (30/234) in
patients receiving placebo. Of the patients who received IMFINZI
(475), 1.1% were fatal and 2.7% were Grade 3 adverse
reactions.
- The incidence of pneumonitis (including radiation pneumonitis)
in patients with LS-SCLC following chemoradiation within 42 days
prior to initiation of IMFINZI in ADRIATIC was 14% (37/262) in
patients receiving IMFINZI and 6% (16/265) in patients receiving
placebo. Of the patients who received IMFINZI (262), 0.4% had a
fatal adverse reaction and 2.7% had Grade 3 adverse reactions.
- The frequency and severity of immune-mediated pneumonitis in
patients who did not receive definitive chemoradiation prior to
IMFINZI were similar in patients who received IMFINZI as a single
agent or with ES-SCLC or BTC when given in combination with
chemotherapy.
- IMFINZI with IMJUDO
- Immune-mediated pneumonitis occurred in 1.3% (5/388) of
patients receiving IMFINZI and IMJUDO, including fatal (0.3%) and
Grade 3 (0.2%) adverse reactions.
- IMFINZI with IMJUDO and Platinum-Based Chemotherapy
- Immune-mediated pneumonitis occurred in 3.5% (21/596) of
patients receiving IMFINZI in combination with IMJUDO and
platinum-based chemotherapy, including fatal (0.5%), and Grade 3
(1%) adverse reactions.
Immune-Mediated Colitis
IMFINZI with IMJUDO and platinum-based chemotherapy can cause
immune-mediated colitis, which may be fatal. IMFINZI and IMJUDO can
cause immune-mediated colitis that is frequently associated with
diarrhea. Cytomegalovirus (CMV) infection/reactivation has been
reported in patients with corticosteroid-refractory immune-mediated
colitis. In cases of corticosteroid-refractory colitis, consider
repeating infectious workup to exclude alternative etiologies.
- IMFINZI as a Single Agent
- Immune-mediated colitis occurred in 2% (37/1889) of patients
receiving IMFINZI, including Grade 4 (<0.1%) and Grade 3 (0.4%)
adverse reactions.
- IMFINZI with IMJUDO
- Immune-mediated colitis or diarrhea occurred in 6% (23/388) of
patients receiving IMFINZI and IMJUDO, including Grade 3 (3.6%)
adverse reactions. Intestinal perforation has been observed in
other studies of IMFINZI and IMJUDO.
- IMFINZI with IMJUDO and Platinum-Based Chemotherapy
- Immune-mediated colitis occurred in 6.5% (39/596) of patients
receiving IMFINZI in combination with IMJUDO and platinum-based
chemotherapy including fatal (0.2%) and Grade 3 (2.5%) adverse
reactions. Intestinal perforation and large intestine perforation
were reported in 0.1% of patients.
Immune-Mediated Hepatitis
IMFINZI and IMJUDO can cause immune-mediated hepatitis, which may
be fatal.
- IMFINZI as a Single Agent
- Immune-mediated hepatitis occurred in 2.8% (52/1889) of
patients receiving IMFINZI, including fatal (0.2%), Grade 4 (0.3%)
and Grade 3 (1.4%) adverse reactions.
- IMFINZI with IMJUDO
- Immune-mediated hepatitis occurred in 7.5% (29/388) of patients
receiving IMFINZI and IMJUDO, including fatal (0.8%), Grade 4
(0.3%) and Grade 3 (4.1%) adverse reactions.
- IMFINZI with IMJUDO and Platinum-Based Chemotherapy
- Immune-mediated hepatitis occurred in 3.9% (23/596) of patients
receiving IMFINZI in combination with IMJUDO and platinum-based
chemotherapy, including fatal (0.3%), Grade 4 (0.5%), and Grade 3
(2%) adverse reactions.
Immune-Mediated
Endocrinopathies
- Adrenal Insufficiency: IMFINZI and IMJUDO can cause
primary or secondary adrenal insufficiency. For Grade 2 or higher
adrenal insufficiency, initiate symptomatic treatment, including
hormone replacement as clinically indicated.
- IMFINZI as a Single Agent
- Immune-mediated adrenal insufficiency occurred in 0.5% (9/1889)
of patients receiving IMFINZI, including Grade 3 (<0.1%) adverse
reactions.
- IMFINZI with IMJUDO
- Immune-mediated adrenal insufficiency occurred in 1.5% (6/388)
of patients receiving IMFINZI and IMJUDO, including Grade 3 (0.3%)
adverse reactions.
- IMFINZI with IMJUDO and Platinum-Based Chemotherapy
- Immune-mediated adrenal insufficiency occurred in 2.2% (13/596)
of patients receiving IMFINZI in combination with IMJUDO and
platinum-based chemotherapy, including Grade 3 (0.8%) adverse
reactions.
- Hypophysitis: IMFINZI and IMJUDO can cause
immune-mediated hypophysitis. Hypophysitis can present with acute
symptoms associated with mass effect such as headache, photophobia,
or visual field cuts. Hypophysitis can cause hypopituitarism.
Initiate symptomatic treatment including hormone replacement as
clinically indicated.
- IMFINZI as a Single Agent
- Grade 3 hypophysitis/hypopituitarism occurred in <0.1%
(1/1889) of patients who received IMFINZI.
- IMFINZI with IMJUDO
- Immune-mediated hypophysitis/hypopituitarism occurred in 1%
(4/388) of patients receiving IMFINZI and IMJUDO.
- IMFINZI with IMJUDO and Platinum-Based Chemotherapy
- Immune-mediated hypophysitis occurred in 1.3% (8/596) of
patients receiving IMFINZI in combination with IMJUDO and
platinum-based chemotherapy, including Grade 3 (0.5%) adverse
reactions.
- Thyroid Disorders (Thyroiditis, Hyperthyroidism, and
Hypothyroidism): IMFINZI and IMJUDO can cause immune-mediated
thyroid disorders. Thyroiditis can present with or without
endocrinopathy. Hypothyroidism can follow hyperthyroidism. Initiate
hormone replacement therapy for hypothyroidism or institute medical
management of hyperthyroidism as clinically indicated.
- IMFINZI as a Single Agent
- Immune-mediated thyroiditis occurred in 0.5% (9/1889) of
patients receiving IMFINZI, including Grade 3 (<0.1%) adverse
reactions.
- Immune-mediated hyperthyroidism occurred in 2.1% (39/1889) of
patients receiving IMFINZI.
- Immune-mediated hypothyroidism occurred in 8.3% (156/1889) of
patients receiving IMFINZI, including Grade 3 (<0.1%) adverse
reactions.
- IMFINZI with IMJUDO
- Immune-mediated thyroiditis occurred in 1.5% (6/388) of
patients receiving IMFINZI and IMJUDO.
- Immune-mediated hyperthyroidism occurred in 4.6% (18/388) of
patients receiving IMFINZI and IMJUDO, including Grade 3 (0.3%)
adverse reactions.
- Immune-mediated hypothyroidism occurred in 11% (42/388) of
patients receiving IMFINZI and IMJUDO.
- IMFINZI with IMJUDO and Platinum-Based Chemotherapy
- Immune-mediated thyroiditis occurred in 1.2% (7/596) of
patients receiving IMFINZI in combination with IMJUDO and
platinum-based chemotherapy.
- Immune-mediated hyperthyroidism occurred in 5% (30/596) of
patients receiving IMFINZI in combination with IMJUDO and
platinum-based chemotherapy, including Grade 3 (0.2%) adverse
reactions.
- Immune-mediated hypothyroidism occurred in 8.6% (51/596) of
patients receiving IMFINZI in combination with IMJUDO and
platinum-based chemotherapy, including Grade 3 (0.5%) adverse
reactions.
- IMFINZI with Carboplatin and Paclitaxel
- Immune-mediated hypothyroidism occurred in 14% (34/235) of
patients receiving IMFINZI in combination with carboplatin and
paclitaxel.
- Type 1 Diabetes Mellitus, which can present with diabetic
ketoacidosis: Monitor patients for hyperglycemia or other signs
and symptoms of diabetes. Initiate treatment with insulin as
clinically indicated.
- IMFINZI as a Single Agent
- Grade 3 immune-mediated Type 1 diabetes mellitus occurred in
<0.1% (1/1889) of patients receiving IMFINZI.
- IMFINZI with IMJUDO
- Two patients (0.5%, 2/388) had events of hyperglycemia
requiring insulin therapy that had not resolved at last
follow-up.
- IMFINZI with IMJUDO and Platinum-Based Chemotherapy
- Immune-mediated Type 1 diabetes mellitus occurred in 0.5%
(3/596) of patients receiving IMFINZI in combination with IMJUDO
and platinum-based chemotherapy including Grade 3 (0.3%) adverse
reactions.
Immune-Mediated Nephritis with Renal
Dysfunction IMFINZI and IMJUDO can cause immune-mediated
nephritis.
- IMFINZI as a Single Agent
- Immune-mediated nephritis occurred in 0.5% (10/1889) of
patients receiving IMFINZI, including Grade 3 (<0.1%) adverse
reactions.
- IMFINZI with IMJUDO
- Immune-mediated nephritis occurred in 1% (4/388) of patients
receiving IMFINZI and IMJUDO, including Grade 3 (0.5%) adverse
reactions.
- IMFINZI with IMJUDO and Platinum-Based Chemotherapy
- Immune-mediated nephritis occurred in 0.7% (4/596) of patients
receiving IMFINZI in combination with IMJUDO and platinum-based
chemotherapy, including Grade 3 (0.2%) adverse reactions.
Immune-Mediated Dermatology
Reactions IMFINZI and IMJUDO can cause immune-mediated
rash or dermatitis. Exfoliative dermatitis, including
Stevens-Johnson Syndrome (SJS), drug rash with eosinophilia and
systemic symptoms (DRESS), and toxic epidermal necrolysis (TEN),
has occurred with PD-1/L-1 and CTLA-4 blocking antibodies. Topical
emollients and/or topical corticosteroids may be adequate to treat
mild to moderate non-exfoliative rashes.
- IMFINZI as a Single Agent
- Immune-mediated rash or dermatitis occurred in 1.8% (34/1889)
of patients receiving IMFINZI, including Grade 3 (0.4%) adverse
reactions.
- IMFINZI with IMJUDO
- Immune-mediated rash or dermatitis occurred in 4.9% (19/388) of
patients receiving IMFINZI and IMJUDO, including Grade 4 (0.3%) and
Grade 3 (1.5%) adverse reactions.
- IMFINZI with IMJUDO and Platinum-Based Chemotherapy
- Immune-mediated rash or dermatitis occurred in 7.2% (43/596) of
patients receiving IMFINZI in combination with IMJUDO and
platinum-based chemotherapy, including Grade 3 (0.3%) adverse
reactions.
Immune-Mediated Pancreatitis
IMFINZI in combination with IMJUDO can cause immune-mediated
pancreatitis. Immune-mediated pancreatitis occurred in 2.3% (9/388)
of patients receiving IMFINZI and IMJUDO, including Grade 4 (0.3%)
and Grade 3 (1.5%) adverse reactions.
Other Immune-Mediated Adverse
Reactions The following clinically significant,
immune-mediated adverse reactions occurred at an incidence of less
than 1% each in patients who received IMFINZI and IMJUDO or were
reported with the use of other immune-checkpoint inhibitors.
- Cardiac/vascular: Myocarditis, pericarditis,
vasculitis.
- Nervous system: Meningitis, encephalitis, myelitis and
demyelination, myasthenic syndrome/myasthenia gravis (including
exacerbation), Guillain-Barré syndrome, nerve paresis, autoimmune
neuropathy.
- Ocular: Uveitis, iritis, and other ocular inflammatory
toxicities can occur. Some cases can be associated with retinal
detachment. Various grades of visual impairment to include
blindness can occur. If uveitis occurs in combination with other
immune-mediated adverse reactions, consider a
Vogt-Koyanagi-Harada-like syndrome, as this may require treatment
with systemic steroids to reduce the risk of permanent vision
loss.
- Gastrointestinal: Pancreatitis including increases in
serum amylase and lipase levels, gastritis, duodenitis.
- Musculoskeletal and connective tissue disorders:
Myositis/polymyositis, rhabdomyolysis and associated sequelae
including renal failure, arthritis, polymyalgia rheumatic.
- Endocrine: Hypoparathyroidism.
- Other (hematologic/immune): Hemolytic anemia, aplastic
anemia, hemophagocytic lymphohistiocytosis, systemic inflammatory
response syndrome, histiocytic necrotizing lymphadenitis (Kikuchi
lymphadenitis), sarcoidosis, immune thrombocytopenia, solid organ
transplant rejection, other transplant (including corneal graft)
rejection.
Infusion-Related Reactions IMFINZI and IMJUDO can cause
severe or life-threatening infusion-related reactions. Monitor for
signs and symptoms of infusion-related reactions. Interrupt, slow
the rate of, or permanently discontinue IMFINZI and IMJUDO based on
the severity. See USPI Dosing and Administration for specific
details. For Grade 1 or 2 infusion-related reactions, consider
using pre-medications with subsequent doses.
- IMFINZI as a Single Agent
- Infusion-related reactions occurred in 2.2% (42/1889) of
patients receiving IMFINZI, including Grade 3 (0.3%) adverse
reactions.
- IMFINZI with IMJUDO
- Infusion-related reactions occurred in 2.6% (10/388) of
patients receiving IMFINZI and IMJUDO.
- IMFINZI with IMJUDO and Platinum-Based Chemotherapy
- Infusion-related reactions occurred in 2.9% (17/596) of
patients receiving IMFINZI in combination with IMJUDO and
platinum-based chemotherapy, including Grade 3 (0.3%) adverse
reactions.
Complications of Allogeneic HSCT after IMFINZI Fatal and
other serious complications can occur in patients who receive
allogeneic hematopoietic stem cell transplantation (HSCT) before or
after being treated with a PD-1/L-1 blocking antibody.
Transplant-related complications include hyperacute
graft-versus-host disease (GVHD), acute GVHD, chronic GVHD, hepatic
veno-occlusive disease (VOD) after reduced intensity conditioning,
and steroid-requiring febrile syndrome (without an identified
infectious cause). These complications may occur despite
intervening therapy between PD-1/L-1 blockade and allogeneic HSCT.
Follow patients closely for evidence of transplant-related
complications and intervene promptly. Consider the benefit versus
risks of treatment with a PD-1/L-1 blocking antibody prior to or
after an allogeneic HSCT.
Embryo-Fetal Toxicity Based on their mechanism of action
and data from animal studies, IMFINZI and IMJUDO can cause fetal
harm when administered to a pregnant woman. Advise pregnant women
of the potential risk to a fetus. In females of reproductive
potential, verify pregnancy status prior to initiating IMFINZI and
IMJUDO and advise them to use effective contraception during
treatment with IMFINZI and IMJUDO and for 3 months after the last
dose of IMFINZI and IMJUDO.
Lactation There is no information regarding the presence
of IMFINZI and IMJUDO in human milk; however, because of the
potential for serious adverse reactions in breastfed infants from
IMFINZI and IMJUDO, advise women not to breastfeed during treatment
and for 3 months after the last dose.
Adverse Reactions Unresectable Stage III NSCLC
- In patients with Stage III NSCLC in the PACIFIC study receiving
IMFINZI (n=475), the most common adverse reactions (≥20%) were
cough (40%), fatigue (34%), pneumonitis or radiation pneumonitis
(34%), upper respiratory tract infections (26%), dyspnea (25%), and
rash (23%). The most common Grade 3 or 4 adverse reactions (≥3%)
were pneumonia (7%) and pneumonitis/radiation pneumonitis
(3.4%).
- In patients with Stage III NSCLC in the PACIFIC study receiving
IMFINZI (n=475), discontinuation due to adverse reactions occurred
in 15% of patients in the IMFINZI arm. Serious adverse reactions
occurred in 29% of patients receiving IMFINZI. The most frequent
serious adverse reactions (≥2%) were pneumonitis or radiation
pneumonitis (7%) and pneumonia (6%). Fatal pneumonitis or radiation
pneumonitis and fatal pneumonia occurred in <2% of patients and
were similar across arms.
Resectable NSCLC
- In patients with resectable NSCLC in the AEGEAN study, the most
common adverse reactions (occurring in ≥20% of patients) were
anemia, nausea, constipation, fatigue, musculoskeletal pain, and
rash.
- In patients with resectable NSCLC in the neoadjuvant phase of
the AEGEAN study receiving IMFINZI in combination with
platinum-containing chemotherapy (n=401), permanent discontinuation
of IMFINZI due to an adverse reaction occurred in 6.7% of patients.
Serious adverse reactions occurred in 21% of patients. The most
frequent (≥1%) serious adverse reactions were pneumonia (2.7%),
anemia (1.5%), myelosuppression (1.5%), vomiting (1.2%),
neutropenia (1%), and acute kidney injury (1%). Fatal adverse
reactions occurred in 2% of patients, including death due to
COVID-19 pneumonia (0.5%), sepsis (0.5%), myocarditis (0.2%),
decreased appetite (0.2%), hemoptysis (0.2%), and death not
otherwise specified (0.2%). Of the 401 IMFINZI treated patients who
received neoadjuvant treatment and 398 placebo-treated patients who
received neoadjuvant treatment, 1.7% (n=7) and 1% (n=4),
respectively, did not receive surgery due to adverse
reactions.
- In patients with resectable NSCLC in the adjuvant phase of the
AEGEAN study receiving IMFINZI as a single agent (n=265), permanent
discontinuation of IMFINZI due to an adverse reaction occurred in
8% of patients. Serious adverse reactions occurred in 13% of
patients. The most frequent serious adverse reactions reported in
>1% of patients were pneumonia (1.9%), pneumonitis (1.1%), and
COVID-19 (1.1%). Four fatal adverse reactions occurred during the
adjuvant phase of the study, including COVID-19 pneumonia,
pneumonia aspiration, interstitial lung disease and aortic
aneurysm.
Metastatic NSCLC
- In patients with mNSCLC in the POSEIDON study receiving IMFINZI
and IMJUDO plus platinum-based chemotherapy (n=330), the most
common adverse reactions (occurring in ≥20% of patients) were
nausea (42%), fatigue (36%), musculoskeletal pain (29%), decreased
appetite (28%), rash (27%), and diarrhea (22%).
- In patients with mNSCLC in the POSEIDON study receiving IMFINZI
in combination with IMJUDO and platinum-based chemotherapy (n=330),
permanent discontinuation of IMFINZI or IMJUDO due to an adverse
reaction occurred in 17% of patients. Serious adverse reactions
occurred in 44% of patients, with the most frequent serious adverse
reactions reported in at least 2% of patients being pneumonia
(11%), anemia (5%), diarrhea (2.4%), thrombocytopenia (2.4%),
pyrexia (2.4%), and febrile neutropenia (2.1%). Fatal adverse
reactions occurred in a total of 4.2% of patients.
Limited-stage Small Cell Lung Cancer
- In patients with limited-stage SCLC in the ADRIATIC study
receiving IMFINZI (n=262), the most common adverse reactions
occurring in ≥20% of patients receiving IMFINZI were pneumonitis or
radiation pneumonitis (38%), and fatigue (21%). The most common
Grade 3 or 4 adverse reactions (≥3%) were pneumonitis or radiation
pneumonitis and pneumonia.
- In patients with limited-stage SCLC in the ADRIATIC study
receiving IMFINZI (n=262), IMFINZI was permanently discontinued due
to adverse reactions in 16% of the patients receiving IMFINZI.
Serious adverse reactions occurred in 30% of patients receiving
IMFINZI. The most frequent serious adverse reactions reported in
≥1% of patients receiving IMFINZI were pneumonitis or radiation
pneumonitis (12%), and pneumonia (5%). Fatal adverse reactions
occurred in 2.7% of patients who received IMFINZI including
pneumonia (1.5%), cardiac failure, encephalopathy and pneumonitis
(0.4% each).
Extensive-stage Small Cell Lung Cancer
- In patients with extensive-stage SCLC in the CASPIAN study
receiving IMFINZI plus chemotherapy (n=265), the most common
adverse reactions (≥20%) were nausea (34%), fatigue/asthenia (32%),
and alopecia (31%). The most common Grade 3 or 4 adverse reaction
(≥3%) was fatigue/asthenia (3.4%).
- In patients with extensive-stage SCLC in the CASPIAN study
receiving IMFINZI plus chemotherapy (n=265), IMFINZI was
discontinued due to adverse reactions in 7% of the patients
receiving IMFINZI plus chemotherapy. Serious adverse reactions
occurred in 31% of patients receiving IMFINZI plus chemotherapy.
The most frequent serious adverse reactions reported in at least 1%
of patients were febrile neutropenia (4.5%), pneumonia (2.3%),
anemia (1.9%), pancytopenia (1.5%), pneumonitis (1.1%), and COPD
(1.1%). Fatal adverse reactions occurred in 4.9% of patients
receiving IMFINZI plus chemotherapy.
Locally Advanced or Metastatic Biliary Tract Cancers
- In patients with locally advanced or metastatic BTC in the
TOPAZ-1 study receiving IMFINZI (n=338), the most common adverse
reactions (occurring in ≥20% of patients) were fatigue (42%),
nausea (40%), constipation (32%), decreased appetite (26%),
abdominal pain (24%), rash (23%), and pyrexia (20%).
- In patients with locally advanced or metastatic BTC in the
TOPAZ-1 study receiving IMFINZI (n=338), discontinuation due to
adverse reactions occurred in 6% of the patients receiving IMFINZI
plus chemotherapy. Serious adverse reactions occurred in 47% of
patients receiving IMFINZI plus chemotherapy. The most frequent
serious adverse reactions reported in at least 2% of patients were
cholangitis (7%), pyrexia (3.8%), anemia (3.6%), sepsis (3.3%) and
acute kidney injury (2.4%). Fatal adverse reactions occurred in
3.6% of patients receiving IMFINZI plus chemotherapy. These include
ischemic or hemorrhagic stroke (4 patients), sepsis (2 patients),
and upper gastrointestinal hemorrhage (2 patients).
Unresectable Hepatocellular Carcinoma
- In patients with unresectable HCC in the HIMALAYA study
receiving IMFINZI and IMJUDO (n=388), the most common adverse
reactions (occurring in ≥20% of patients) were rash (32%), diarrhea
(27%), fatigue (26%), pruritus (23%), musculoskeletal pain (22%),
and abdominal pain (20%).
- In patients with unresectable HCC in the HIMALAYA study
receiving IMFINZI and IMJUDO (n=388), serious adverse reactions
occurred in 41% of patients. Serious adverse reactions in >1% of
patients included hemorrhage (6%), diarrhea (4%), sepsis (2.1%),
pneumonia (2.1%), rash (1.5%), vomiting (1.3%), acute kidney injury
(1.3%), and anemia (1.3%). Fatal adverse reactions occurred in 8%
of patients who received IMFINZI and IMJUDO, including death (1%),
hemorrhage intracranial (0.5%), cardiac arrest (0.5%), pneumonitis
(0.5%), hepatic failure (0.5%), and immune-mediated hepatitis
(0.5%). Permanent discontinuation of treatment regimen due to an
adverse reaction occurred in 14% of patients.
Primary advanced or Recurrent dMMR Endometrial Cancer
- In patients with advanced or recurrent dMMR endometrial cancer
in the DUO-E study receiving IMFINZI in combination with
carboplatin and paclitaxel followed by IMFINZI as a single-agent
(n=44), the most common adverse reactions, including laboratory
abnormalities (occurring in >20% of patients) were peripheral
neuropathy (61%), musculoskeletal pain (59%), nausea (59%),
alopecia (52%), fatigue (41%), abdominal pain (39%), constipation
(39%), rash (39%), decreased magnesium (36%), increased ALT (32%),
increased AST (30%), diarrhea (27%), vomiting (27%), cough (27%),
decreased potassium (25%), dyspnea (25%), headache (23%), increased
alkaline phosphatase (20%), and decreased appetite (18%). The most
common Grade 3 or 4 adverse reactions (≥3%) were constipation
(4.5%) and fatigue (4.5%).
- In patients with advanced or recurrent dMMR endometrial cancer
in the DUO-E study receiving IMFINZI in combination with
carboplatin and paclitaxel followed by IMFINZI as a single-agent
(n=44), permanent discontinuation of IMFINZI due to adverse
reactions occurred in 11% of patients. Serious adverse reactions
occurred in 30% of patients who received IMFINZI with carboplatin
and paclitaxel; the most common serious adverse reactions (≥4%)
were constipation (4.5%) and rash (4.5%).
The safety and effectiveness of IMFINZI and IMJUDO have not been
established in pediatric patients.
Indications:
IMFINZI, as a single agent, is indicated for the treatment of
adult patients with unresectable Stage III non-small cell lung
cancer (NSCLC) whose disease has not progressed following
concurrent platinum-based chemotherapy and radiation therapy
(cCRT).
IMFINZI in combination with platinum-containing chemotherapy as
neoadjuvant treatment, followed by IMFINZI continued as a single
agent as adjuvant treatment after surgery, is indicated for the
treatment of adult patients with resectable (tumors ≥4 cm and/or
node positive) NSCLC and no known epidermal growth factor receptor
(EGFR) mutations or anaplastic lymphoma kinase (ALK)
rearrangements.
IMFINZI, in combination with IMJUDO and platinum-based
chemotherapy, is indicated for the treatment of adult patients with
metastatic NSCLC with no sensitizing EGFR mutations or ALK genomic
tumor aberrations.
IMFINZI, as a single agent, is indicated for the treatment of
adult patients with limited-stage small cell lung cancer (LS-SCLC)
whose disease has not progressed following concurrent
platinum-based chemotherapy and radiation therapy (cCRT).
IMFINZI, in combination with etoposide and either carboplatin or
cisplatin, is indicated for the first-line treatment of adult
patients with extensive-stage small cell lung cancer (ES-SCLC).
IMFINZI, in combination with gemcitabine and cisplatin, is
indicated for the treatment of adult patients with locally advanced
or metastatic biliary tract cancer (BTC).
IMFINZI in combination with IMJUDO is indicated for the
treatment of adult patients with unresectable hepatocellular
carcinoma (uHCC).
IMFINZI in combination with carboplatin and paclitaxel followed
by IMFINZI as a single agent is indicated for the treatment of
adult patients with primary advanced or recurrent endometrial
cancer that is mismatch repair deficient (dMMR).
Please see additional Important Safety Information throughout
and Full Prescribing Information including Medication Guide for
IMFINZI and IMJUDO.
You may report side effects related to AstraZeneca products
(opens new window).
Notes
Muscle-invasive bladder cancer Bladder cancer is the 9th
most common cancer in the world, with more than 614,000 patients
diagnosed each year.6 The most common type of bladder cancer is
urothelial carcinoma, which begins in the urothelial cells of the
urinary tract.7 Approximately 50% of patients who undergo bladder
removal surgery experience disease recurrence.5 Treatment options
that prevent disease recurrence after surgery are critically needed
in this curative-intent setting.
NIAGARA NIAGARA is a randomized, open-label,
multi-center, global Phase III trial evaluating perioperative
IMFINZI as treatment for patients with MIBC before and after
radical cystectomy. In the trial, 1,063 patients were randomized to
receive IMFINZI plus neoadjuvant chemotherapy prior to cystectomy
followed by IMFINZI, or neoadjuvant chemotherapy alone prior to
cystectomy with no further treatment after surgery. NIAGARA is the
largest global Phase III trial in this setting.
The trial is being conducted at 192 centers across 22 countries
including in North America, South America, Europe, Australia and
Asia. Its dual primary endpoints are EFS and pathologic complete
response. Key secondary endpoints are OS and safety.
IMFINZI IMFINZI® (durvalumab) is a human monoclonal
antibody that binds to the PD-L1 protein and blocks the interaction
of PD-L1 with the PD-1 and CD80 proteins, countering the tumor's
immune-evading tactics and releasing the inhibition of immune
responses.
IMFINZI is the only approved immunotherapy and the global
standard of care in the curative-intent setting of unresectable,
Stage III non-small cell lung cancer (NSCLC) in patients whose
disease has not progressed after chemoradiotherapy. Additionally,
IMFINZI is approved for limited-stage small cell lung cancer (SCLC)
in patients whose disease has not progressed following concurrent
platinum-based chemoradiotherapy; as a perioperative treatment in
combination with neoadjuvant chemotherapy in resectable NSCLC; in
combination with chemotherapy (etoposide and either carboplatin or
cisplatin) for the treatment of extensive-stage SCLC; and in
combination with a short course of IMJUDO® (tremelimumab-actl) and
chemotherapy for the treatment of metastatic NSCLC.
In addition to its indications in lung cancers, IMFINZI is
approved in combination with chemotherapy (gemcitabine plus
cisplatin) in locally advanced or metastatic biliary tract cancer
and in combination with IMJUDO in unresectable hepatocellular
carcinoma (HCC). IMFINZI is also approved as a monotherapy in
unresectable HCC in Japan and the EU.
IMFINZI is also approved in combination with chemotherapy
(carboplatin and paclitaxel) followed by IMFINZI monotherapy in
primary advanced or recurrent endometrial cancer that is mismatch
repair deficient (dMMR) in the US. In the EU, IMFINZI plus
chemotherapy followed by olaparib and IMFINZI is approved for
patients with mismatch repair proficient (pMMR) advanced or
recurrent endometrial cancer, and IMFINZI plus chemotherapy
followed by IMFINZI alone is approved for patients with dMMR
disease. In Japan, IMFINZI plus chemotherapy followed by IMFINZI
monotherapy has also been approved as 1st-line treatment in primary
advanced or recurrent endometrial cancer, and IMFINZI plus
chemotherapy followed by IMFINZI and olaparib has been approved for
patients with pMMR disease.
Since the first approval in May 2017, more than 374,000 patients
have been treated with IMFINZI. As part of a broad development
program, IMFINZI is being tested as a single treatment and in
combination with other anti-cancer treatments for patients with
SCLC, NSCLC, bladder cancer, breast cancer, several
gastrointestinal and gynecologic cancers, and other solid
tumors.
AstraZeneca in immuno-oncology (IO) AstraZeneca is a
pioneer in introducing the concept of immunotherapy into dedicated
clinical areas of high unmet medical need. The Company has a
comprehensive and diverse IO portfolio and pipeline anchored in
immunotherapies designed to overcome evasion of the anti-tumor
immune response and stimulate the body’s immune system to attack
tumors.
AstraZeneca strives to redefine cancer care and help transform
outcomes for patients with IMFINZI as a monotherapy and in
combination with IMJUDO as well as other novel immunotherapies and
modalities. The Company is also investigating next-generation
immunotherapies like bispecific antibodies and therapeutics that
harness different aspects of immunity to target cancer, including
cell therapy and T-cell engagers.
AstraZeneca is pursuing an innovative clinical strategy to bring
IO-based therapies that deliver long-term survival to new settings
across a wide range of cancer types. The Company is focused on
exploring novel combination approaches to help prevent treatment
resistance and drive longer immune responses. With an extensive
clinical program, the Company also champions the use of IO
treatment in earlier disease stages, where there is the greatest
potential for cure.
AstraZeneca in oncology AstraZeneca is leading a
revolution in oncology with the ambition to provide cures for
cancer in every form, following the science to understand cancer
and all its complexities to discover, develop and deliver
life-changing medicines to patients.
The Company’s focus is on some of the most challenging cancers.
It is through persistent innovation that AstraZeneca has built one
of the most diverse portfolios and pipelines in the industry, with
the potential to catalyze changes in the practice of medicine and
transform the patient experience.
AstraZeneca has the vision to redefine cancer care and, one day,
eliminate cancer as a cause of death.
AstraZeneca AstraZeneca is a global, science-led
biopharmaceutical company that focuses on the discovery,
development and commercialization of prescription medicines in
Oncology, Rare Diseases and BioPharmaceuticals, including
Cardiovascular, Renal & Metabolism, and Respiratory &
Immunology. Based in Cambridge, UK, AstraZeneca operates in over
125 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 social media
@AstraZeneca.
References
- FDA. Priority Review. Available at:
https://www.fda.gov/patients/fast-track-breakthrough-therapy-accelerated-approval-priority-review/priority-review.
Accessed December 2024.
- Burger M, et al. Epidemiology and Risk Factors of Urothelial
Bladder Cancer. Eur Urol. 2013;63(2):234-241.
- National Collaborating Centre for Cancer. Bladder Cancer:
Diagnosis and Management. London: National Institute for Health and
Care Excellence (NICE). Available at:
https://www.ncbi.nlm.nih.gov/books/NBK356289. Accessed December
2024.
- Cerner CancerMPact database. Accessed December 2024. Reflects
epidemiology estimates across G8 countries (US, EU, Japan,
China).
- Witjes JA, et al. EAU Guidelines on Muscle-invasive and
Metastatic Bladder Cancer. Eur Urol. 2021;1-94.
- World Health Organization. International Agency for Research on
Cancer. Bladder Fact Sheet. Available at:
https://gco.iarc.who.int/media/globocan/factsheets/cancers/30-bladder-fact-sheet.pdf.
Accessed December 2024.
- American Cancer Society. What Is Bladder Cancer? Available at:
https://www.cancer.org/cancer/bladder-cancer/about/what-is-bladder-cancer.html.
Accessed December 2024.
US-96518 Last Updated 12/24
View source
version on businesswire.com: https://www.businesswire.com/news/home/20241206025636/en/
Media Inquiries Brendan McEvoy +1 302 885 2677 Chelsea
Tressler +1 302 855 2677
US Media Mailbox: usmediateam@astrazeneca.com
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