57% of patients treated with IMFINZI were
alive at three years in ADRIATIC Phase III trial
Positive results from the ADRIATIC Phase III trial showed
AstraZeneca’s IMFINZI® (durvalumab) demonstrated statistically
significant and clinically meaningful improvements in the dual
primary endpoints of overall survival (OS) and progression-free
survival (PFS) compared to placebo for patients with limited-stage
small cell lung cancer (LS-SCLC) who had not progressed following
standard-of-care concurrent chemoradiotherapy (cCRT).
These results will be presented today during the Plenary Session
at the 2024 American Society of Clinical Oncology (ASCO) Annual
Meeting (abstract #LBA5).
Results from the planned interim analysis showed IMFINZI reduced
the risk of death by 27% versus placebo (based on an 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 versus
33.4 months for placebo. 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 PFS HR of 0.76; 95% CI 0.61-0.95; p=0.0161) versus
placebo. Median PFS was 16.6 months for IMFINZI versus 9.2 months
for placebo. An estimated 46% of patients treated with IMFINZI had
not experienced disease progression at two years compared to 34% on
placebo.
The OS and PFS benefits observed were generally consistent
across key prespecified patient subgroups including age, sex, race,
disease stage1 at diagnosis, prior radiation and whether patients
received prophylactic cranial irradiation.
David R. Spigel, MD, Chief Scientific Officer at Sarah Cannon
Research Institute and investigator in the trial, said: “The
ADRIATIC results represent a breakthrough in limited-stage small
cell lung cancer, a highly aggressive disease where recurrence
rates are high and only 15 to 30 per cent of patients survive five
years. Durvalumab is the first systemic treatment to show improved
survival for these patients in decades and should become a new
standard of care in this setting.”
Susan Galbraith, Executive Vice President, Oncology R&D,
AstraZeneca, said: “The strong improvement in overall survival seen
with IMFINZI after concurrent chemoradiotherapy is transformative
in the treatment of limited-stage small cell lung cancer. These
tremendous results underscore our ambition to drive up survival
rates in this earlier-stage lung cancer setting, and we look
forward to working with regulatory authorities to bring IMFINZI to
these patients as quickly as possible.”
Summary of results: ADRIATIC
IMFINZI
(n=264)
Placebo
(n=266)
OS
Median OS, in months (95% CI)
55.9
(37.3-NEi)
33.4
(25.5-39.9)
Hazard ratio (95% CI)
0.73 (0.57-0.93)
p-value
0.0104
OS rate at 24 months (%)
68.0
58.5
OS rate at 36 months (%)
56.5
47.6
PFS
Median PFS, in months (95% CI)
16.6
(10.2-28.2)
9.2
(7.4-12.9)
Hazard ratio (95% CI)
0.76 (0.61-0.95)
p-value
0.0161
PFS rate at 18 months (%)
48.8
36.1
PFS rate at 24 months (%)
46.2
34.2
i Not estimable
The safety profile for IMFINZI was generally manageable and
consistent with the known profile of this medicine. No new safety
signals were observed. Grade 3 and 4 adverse events due to any
cause occurred in 24.4% of patients treated with IMFINZI and 24.2%
of patients treated on placebo.
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
- Immunemediated 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
- Immunemediated 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
- Immunemediated 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.
- 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 patients.
- 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.
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).
Please see Full Prescribing Information including Medication
Guide for IMFINZI and IMJUDO.
You may report side effects related to AstraZeneca products by
clicking here.
Notes
Small cell lung cancer
Lung cancer is the leading cause of cancer death among men and
women and accounts for about one-fifth of all cancer deaths.2 Lung
cancer is broadly split into non-small cell lung cancer and SCLC,
with about 15% of cases classified as SCLC, a highly aggressive
form of the disease.3-4
LS-SCLC (Stage I-III), which accounts for approximately 30% of
SCLC diagnoses, is classified as SCLC that is generally only in one
lung or one side of the chest.5-6 LS-SCLC typically recurs and
progresses rapidly despite initial response to standard-of-care
chemotherapy and radiotherapy.4,7 The prognosis for LS-SCLC is
particularly poor, as only 15-30% of patients will be alive five
years after diagnosis.8
ADRIATIC
The ADRIATIC trial is a randomized, double-blind,
placebo-controlled, multi-center global Phase III trial evaluating
IMFINZI monotherapy and IMFINZI plus IMJUDO 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® (durvalumab)
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 currently approved in a number of countries across
multiple types of lung cancer. 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 chemoradiation therapy. IMFINZI 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.
In addition to its indications in lung cancers, IMFINZI is
approved in a number of countries 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
previously treated patients with advanced bladder cancer in a small
number of countries.
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, bladder cancer, breast cancer, several
gastrointestinal 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 100 countries and its innovative
medicines are used by millions of patients worldwide. Please visit
www.astrazeneca-us.com and follow us on social media
@AstraZeneca.
References
- American Joint Committee on Cancer disease stage.
- World Health Organization. International Agency for Research on
Cancer. Lung Fact Sheet. Available at:
https://gco.iarc.who.int/media/globocan/factsheets/cancers/15-trachea-bronchus-and-lung-fact-sheet.pdf.
Accessed May 2024.
- LUNGevity Foundation. Types of Lung Cancer. Available at:
https://lungevity.org/for-patients-caregivers/lung-cancer-101/types-of-lung-cancer.
Accessed May 2024.
- National Cancer Institute. NCI Dictionary - Small Cell Lung
Cancer. Available at:
https://www.cancer.gov/publications/dictionaries/cancer-terms/def/small-cell-lung-cancer.
Accessed May 2024.
- American Cancer Society. Treatment Choices by Stage for Small
Cell Lung Cancer. Available at:
https://www.cancer.org/cancer/lung-cancer/treating-small-cell/by-stage.html.
Accessed May 2024.
- 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.
- Qin A, et al. 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.
US-90208 Last Updated 06/24
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Media Inquiries Brendan McEvoy, +1 302 885 2677 Chelsea
Tressler, +1 302 885 2677 US Media Mailbox:
usmediateam@astrazeneca.com
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