Based on ADRIATIC Phase III trial which
demonstrated statistically significant and clinically meaningful
overall survival and progression-free survival benefit
AstraZeneca’s supplemental Biologics License Application (sBLA)
for IMFINZI® (durvalumab), based on the results from the positive
ADRIATIC Phase III trial in patients with limited-stage small cell
lung cancer (LS-SCLC) whose disease has not progressed following
platinum-based concurrent chemoradiotherapy (cCRT), has been
accepted and granted Priority Review in the US.
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 fourth quarter of 2024.
IMFINZI was also recently granted Breakthrough Therapy
Designation (BTD) by the FDA in this setting. BTD accelerates the
development and regulatory review of potential new medicines
intended to treat a serious condition and address a significant
unmet medical need.2
Small cell lung cancer (SCLC) is a highly aggressive form of
lung cancer that typically recurs and progresses rapidly despite
initial response to chemotherapy and radiotherapy in LS-SCLC
patients.3-4 The prognosis for LS-SCLC is particularly poor, as
only 15-30% of these patients will be alive five years after
diagnosis.5
Susan Galbraith, Executive Vice President, Oncology R&D,
AstraZeneca, said: “This Priority Review reinforces the potential
of IMFINZI to transform outcomes for patients as the first and only
immunotherapy to demonstrate a survival benefit in limited-stage
small cell lung cancer. There is an urgent need for new treatment
options that improve upon the standard of care in this setting,
which has not changed in forty years, and we look forward to
working with the FDA to bring IMFINZI to patients as quickly as
possible.”
The sBLA is based on data from the ADRIATIC Phase III trial
recently presented during the Plenary Session at the 2024 American
Society of Clinical Oncology (ASCO) Annual Meeting.
In the trial, IMFINZI reduced the risk of death by 27% versus
placebo (based on an overall survival [OS] hazard ratio [HR] of
0.73; 95% confidence interval [CI] 0.57-0.93; P=0.0104). Estimated
median OS was 55.9 months for IMFINZI (95% CI 37.3-not estimable
[NE]) versus 33.4 months for placebo (95% CI 25.5-39.9). An
estimated 57% of patients treated with IMFINZI were alive at three
years compared to 48% on placebo.
IMFINZI also reduced the risk of disease progression or death by
24% (based on a progression-free survival [PFS] HR of 0.76; 95% CI
0.61-0.95; P=0.0161) versus placebo. Median PFS was 16.6 months for
IMFINZI (95% CI 10.2-28.2) versus 9.2 months for placebo (95% CI
7.4-12.9). An estimated 46% of patients treated with IMFINZI had
not experienced disease progression at two years compared to 34% on
placebo.
The safety profile for IMFINZI was generally manageable and
consistent with the known profile of this medicine. No new safety
signals were observed.
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 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 10 (2.6%) 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
- 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.
- 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 patient
- 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.
- 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).
- 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.
- 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 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.
IMFINZI, in combination with IMJUDO and platinum-based
chemotherapy, is indicated for the treatment of adult patients with
metastatic NSCLC with no sensitizing epidermal growth factor
receptor (EGFR) mutations or anaplastic lymphoma kinase (ALK)
genomic tumor aberrations.
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 Full Prescribing Information including Medication
Guide for IMFINZI and IMJUDO.
Notes
Small cell lung cancer Lung cancer is the leading cause
of cancer death among men and women, accounting for about one-fifth
of all cancer deaths.6-7 Lung cancer is broadly split into
non-small cell lung cancer (NSCLC) and SCLC, with about 15% of
cases classified as SCLC.8
LS-SCLC (Stage I-III) is classified as SCLC that is generally
only in one lung or one side of the chest.9 LS-SCLC accounts for
approximately 30% of SCLC diagnoses and the prognosis remains poor
despite curative-intent treatment with standard-of-care cCRT.10
ADRIATIC The ADRIATIC trial is a randomized,
double-blind, placebo-controlled, multi-center global Phase III
trial evaluating IMFINZI monotherapy and IMFINZI plus IMJUDO®
(tremelimumab-actl) versus placebo in the treatment of 730 patients
with LS-SCLC who had not progressed following cCRT. In the
experimental arms, patients were randomized to receive a 1500 mg
fixed dose of IMFINZI with or without IMJUDO 75 mg every four weeks
for up to four doses/cycles each, followed by IMFINZI every four
weeks for up to 24 months.
The dual primary endpoints were PFS and OS for IMFINZI
monotherapy versus placebo. Key secondary endpoints included OS and
PFS for IMFINZI plus IMJUDO versus placebo, safety and quality of
life measures. The trial included 164 centers in 19 countries
across North and South America, Europe and Asia.
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 NSCLC in patients whose disease has not progressed after
chemoradiotherapy. IMFINZI in combination with chemotherapy
(etoposide and either carboplatin or cisplatin) is also approved
for the treatment of extensive-stage SCLC and in combination with a
short course of IMJUDO and chemotherapy for the treatment of
metastatic NSCLC.
IMFINZI also demonstrated statistically significant and
clinically meaningful event-free survival results in patients with
resectable early-stage NSCLC based on the AEGEAN Phase III trial.
IMFINZI in combination with neoadjuvant chemotherapy before surgery
and as adjuvant monotherapy after surgery is approved for patients
in the UK, Switzerland and Taiwan (China) based on this trial.
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 and in combination with
chemotherapy (carboplatin plus paclitaxel) followed by IMFINZI
monotherapy in primary advanced or recurrent endometrial cancer
that is mismatch repair deficient in the US.
Since the first approval in May 2017, more than 220,000 patients
have been treated with IMFINZI. As part of a broad development
program, IMFINZI is being tested as a single treatment and in
combinations with other anti-cancer treatments for patients with
SCLC, NSCLC, breast cancer, bladder cancer, several
gastrointestinal and gynecologic cancers, and other solid
tumors.
AstraZeneca in lung cancer AstraZeneca is working to
bring patients with lung cancer closer to cure through the
detection and treatment of early-stage disease, while also pushing
the boundaries of science to improve outcomes in the resistant and
advanced settings. By defining new therapeutic targets and
investigating innovative approaches, the Company aims to match
medicines to the patients who can benefit most.
The Company’s comprehensive portfolio includes leading lung
cancer medicines and the next wave of innovations, including
osimertinib and gefitinib; IMFINZI and IMJUDO; fam-trastuzumab
deruxtecan-nxki and datopotamab deruxtecan in collaboration with
Daiichi Sankyo; savolitinib in collaboration with HUTCHMED; as well
as a pipeline of potential new medicines and combinations across
diverse mechanisms of action.
AstraZeneca is a founding member of the Lung Ambition Alliance,
a global coalition working to accelerate innovation and deliver
meaningful improvements for people with lung cancer, including and
beyond treatment.
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. Accessed August 2024. Available at:
https://www.fda.gov/patients/fast-track-breakthrough-therapy-accelerated-approval-priority-review/priority-review
- FDA. Frequently asked questions: breakthrough therapies.
Accessed August 2024. Available at:
https://www.fda.gov/regulatory-information/food-and-drug-administration-safety-and-innovation-act-fdasia/frequently-asked-questions-breakthrough-therapies
- National Cancer Institute. NCI dictionary - small cell lung
cancer. Accessed August 2024. Available at:
https://www.cancer.gov/publications/dictionaries/cancer-terms/def/small-cell-lung-cancer
- Qin A, Kalemkerian GP. Treatment options for relapsed
small-cell lung cancer: what progress have we made? J Oncol Pract.
2018;14(6):369-370.
- Bebb DG, et al. Symptoms and experiences with small cell lung
cancer: a mixed methods study of patients and caregivers. Pulm
Ther. 2023;9:435-450.
- World Health Organization. International agency for research on
cancer. lung fact sheet. Accessed August 2024. Available at:
https://gco.iarc.who.int/media/globocan/factsheets/cancers/15-trachea-bronchus-and-lung-fact-sheet.pdf
- World Health Organization. International agency for research on
cancer. world fact sheet. Accessed August 2024. Available at:
https://gco.iarc.who.int/media/globocan/factsheets/populations/900-world-fact-sheet.pdf
- LUNGevity Foundation. Types of lung cancer. Accessed August
2024. Available at:
https://lungevity.org/for-patients-caregivers/lung-cancer-101/types-of-lung-cancer.
- American Cancer Society. Treatment choices for small cell lung
cancer, by stage. Accessed August 2024. Available at:
https://www.cancer.org/cancer/lung-cancer/treating-small-cell/by-stage.html.
- Senan S, et al. ADRIATIC: A phase III trial of durvalumab ±
tremelimumab after concurrent chemoradiation for patients with
limited stage small cell lung cancer. Ann Oncol. 2019;30(suppl.
2):ii25.
US-92607 Last Updated 8/24
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version on businesswire.com: https://www.businesswire.com/news/home/20240815340200/en/
Media Inquiries Brendan McEvoy, +1 302 885 2677 Chelsea
Tressler, +1 302 885 2677 US Media Mailbox:
usmediateam@astrazeneca.com
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