Longest survival follow-up ever reported for
a Phase III immunotherapy trial in this setting
Updated results from the HIMALAYA Phase III trial showed
AstraZeneca’s IMFINZI® (durvalumab) plus IMJUDO®
(tremelimumab-actl) demonstrated a sustained, clinically meaningful
overall survival (OS) benefit at five years for patients with
unresectable hepatocellular carcinoma (HCC) who had not received
prior systemic therapy and were not eligible for localized
treatment.
These results from HIMALAYA will be presented today at the
European Society for Medical Oncology (ESMO) Congress 2024 in
Barcelona, Spain (presentation 947MO).
At five years of follow-up, this latest exploratory analysis
showed that a single priming dose of IMJUDO added to IMFINZI,
called the STRIDE regimen (Single Tremelimumab-actl Regular
Interval Durvalumab), reduced the risk of death by 24% compared to
sorafenib (based on a hazard ratio [HR] of 0.76; 95% confidence
interval [CI] 0.65-0.89). An estimated 19.6% of patients treated
with the STRIDE regimen were alive at five years versus 9.4% for
those treated with sorafenib.
In a subgroup analysis of patients in the trial who achieved
disease control, defined as complete or partial response or stable
disease, 28.7% of those treated with the STRIDE regimen were alive
at five years versus 12.7% of patients treated with sorafenib. In
addition, an exploratory analysis of depth of response (DpR) showed
that more patients treated with the STRIDE regimen experienced deep
responses leading to longer survival compared to sorafenib.
Lorenza Rimassa, MD, Associate Professor of Medical Oncology,
Humanitas University and IRCCS Humanitas Research Hospital, Milan,
Italy and a lead investigator in the HIMALAYA trial, said:
“Treatment with durvalumab plus tremelimumab-actl for patients with
advanced liver cancer doubled the overall survival rate at five
years, a significant survival advantage over sorafenib that has
also become even more pronounced over time. These data reinforce
the use of this novel dual immunotherapy regimen and are an
important milestone for patients with this devastating
disease.”
Sarah Manes, Liver Cancers Program Director at Global Liver
Institute, said: “Reaching the five-year survival milestone is both
clinically significant and emotionally meaningful for people with
advanced liver cancer and their families. We are thrilled to see
this progress in improving outcomes with new treatment options,
bringing new hope for long-term survivorship to patients in our
community.”
Susan Galbraith, Executive Vice President, Oncology R&D,
AstraZeneca, said: “It is remarkable to see nearly 20 percent of
patients with advanced liver cancer treated with the STRIDE regimen
alive at five years compared to only about seven percent of
patients living that long historically. This is a major step
forward, setting a new survival benchmark. This underscores our
commitment to following patients for the long term to help us
better characterize the enduring clinical benefits of this
innovative priming approach with an anti-CTLA-4 antibody added to
PD-L1 blockade.”
Summary of updated survival results: HIMALAYA
OSi, ii
STRIDE
(n=393)
Sorafenib
(n=389)
Median duration of follow-up, in months
(95% CI)
62.5 (59.5, 64.8)
59.9 (58.3, 61.5)
OS HR (95% CI)
0.76 (0.65-0.89)
p-value (2-sided)iii
0.0008
OS rateiv at 60 months (95% CI), %
19.6
9.4
DC at 60 months
Number of patients
43
17
OS rate, %
28.7
12.7
DpRv >75% at 60 months
Number of patients
27
3
OS rateiv, %
72.7
33.3
DpRv >50% - ≤75% at 60 months
Number of patients
34
12
OS rateiv, %
57.8
32.1
i. Updated analysis data cut-off: 01 March
2024, with 82% OS data maturity
ii. OS HRs and 95% CIs were calculated
using a Cox proportional hazards model adjusting for treatment,
aetiology, ECOG performance status, and macrovascular invasion
iii. Nominal p-value
iv. OS rates at 60 months were estimated
using Kaplan-Meier method
v. DpR represents the percentage of tumor
shrinkage from baseline observed at the time of best objective
response evaluation
The safety profile of the STRIDE regimen was consistent with the
known profiles of each medicine, and no new safety signals were
observed with longer follow-up. Serious treatment-related adverse
events, defined as Grade 3 or 4 and including death, were
experienced by 17.5% of patients treated with the STRIDE regimen
versus 9.9% of patients treated with sorafenib, with no new events
occurring after the primary analysis for STRIDE.
IMFINZI in combination with IMJUDO is approved for the treatment
of adults with advanced or unresectable HCC in the US, EU (in the
1st-line setting), Japan and several other countries. IMFINZI
monotherapy is also approved in Japan in this setting.
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 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.
- 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
Liver cancer Liver cancer, of which HCC is the most
common type, is the third-leading cause of cancer death, with
nearly 900,000 people worldwide diagnosed each year and a high
prevalence in certain regions of Asia.1-2 An estimated 80-90% of
all patients with HCC also have cirrhosis. Chronic liver diseases
such as cirrhosis are associated with inflammation that over time
can lead to the development of HCC.3
Advanced-stage HCC prognosis is poor, with a five-year survival
rate of only 7%.4 More than half of patients are diagnosed at
advanced stages of the disease, often when symptoms first appear.5
The unique immune environment of liver cancer provides clear
rationale for investigating medications that harness the power of
the immune system to treat HCC.5
HIMALAYA HIMALAYA is a randomized, open-label,
multi-center, global Phase III trial of IMFINZI monotherapy and a
regimen comprising a single priming dose of IMJUDO 300 mg added to
IMFINZI 1500mg followed by IMFINZI every four weeks (STRIDE
regimen) versus sorafenib, a standard-of-care multi-kinase
inhibitor.
The trial included a total of 1,324 randomized patients with
unresectable, advanced HCC who had not been treated with prior
systemic therapy and were not eligible for locoregional therapy
(treatment localized to the liver and surrounding tissue).
The trial was conducted in 181 centers across 16 countries,
including in the US, Canada, Europe, South America and Asia. The
primary endpoint was OS for the combination versus sorafenib and
key secondary endpoints included OS for IMFINZI versus sorafenib,
objective response rate and progression-free survival (PFS) for the
combination and for IMFINZI alone.
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 approved in combination with chemotherapy
(gemcitabine plus cisplatin) in locally advanced or metastatic
biliary tract cancer (BTC) and in combination with IMJUDO®
(tremelimumab-actl) in unresectable 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.
In addition to its indications in gastrointestinal (GI) cancers,
IMFINZI is 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. IMFINZI is also approved for the treatment of
extensive-stage small cell lung cancer (SCLC) and in combination
with a short course of IMJUDO and chemotherapy for the treatment of
metastatic NSCLC. In limited-stage SCLC, IMFINZI demonstrated
statistically significant and clinically meaningful improvements in
the dual primary endpoints of OS and PFS compared to placebo in
patients who had not progressed following standard-of-care
concurrent chemoradiotherapy in the ADRIATIC Phase III trial.
IMFINZI in combination with neoadjuvant platinum-containing
chemotherapy before surgery and as adjuvant monotherapy after
surgery has been approved for patients in the US and several other
countries for the treatment of adult patients with resectable NSCLC
and no known epidermal growth factor receptor mutations or
anaplastic lymphoma kinase rearrangements.
IMFINZI plus chemotherapy followed by IMFINZI alone was recently
approved in the US for mismatch repair deficient patients with
primary advanced or recurrent endometrial cancer. This regimen was
also approved in the EU, in addition to IMFINZI plus chemotherapy
followed by IMFINZI and olaparib for mismatch repair proficient
patients.
In muscle-invasive bladder cancer, IMFINZI in combination with
chemotherapy demonstrated a statistically significant and
clinically meaningful improvement in the primary endpoint of
event-free survival and the key secondary endpoint of OS versus
neoadjuvant chemotherapy in the NIAGARA Phase III trial.
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 GI and
gynecologic cancers other solid tumors.
IMJUDO IMJUDO® (tremelimumab-actl) is a human monoclonal
antibody that targets the activity of cytotoxic
T-lymphocyte-associated protein 4 (CTLA-4). IMJUDO blocks the
activity of CTLA-4, contributing to T-cell activation, priming the
immune response to cancer and fostering cancer cell death. In
addition to its approved indications in liver and lung cancers,
IMJUDO is being tested in combination with IMFINZI across multiple
tumor types including locoregional HCC (EMERALD-3), SCLC (ADRIATIC)
and bladder cancer (VOLGA and NILE).
AstraZeneca in GI cancers AstraZeneca has a broad
development program for the treatment of GI cancers across several
medicines and a variety of tumor types and stages of disease. In
2022, GI cancers collectively represented approximately 4.9 million
new cancer cases leading to approximately 3.3 million deaths.6
Within this program, the Company is committed to improving
outcomes in gastric, liver, biliary tract, esophageal, pancreatic
and colorectal cancers.
In addition to its indications in BTC and HCC, IMFINZI is being
assessed in combinations, including with IMJUDO, in liver,
esophageal and gastric cancers in an extensive development program
spanning early to late-stage disease across settings.
The Company is also assessing rilvegostomig (AZD2936), a
PD-1/TIGIT bispecific antibody, in combination with chemotherapy as
an adjuvant therapy in BTC and as a 1st-line treatment in patients
with HER2-negative, locally advanced unresectable or metastatic
gastroesophageal junction cancers.
Fam-trastuzumab deruxtecan-nxki, a HER2-directed antibody drug
conjugate, is approved in the US, China and several other countries
for HER2-positive advanced gastric cancer and is being assessed in
colorectal cancer. It also has been assessed in multiple GI
settings including BTC in the DESTINY-PanTumor02 Phase II trial,
and it was recently approved in the US for the treatment of
unresectable or metastatic HER2-positive solid tumors who have
received prior systemic treatment and have no satisfactory
alternative treatment options. Fam-trastuzumab deruxtecan-nxki is
jointly developed and commercialized by AstraZeneca and Daiichi
Sankyo.
Olaparib, a first-in-class PARP inhibitor, is approved in the
US, EU and several other countries for the treatment of
BRCA-mutated metastatic pancreatic cancer. Olaparib is developed
and commercialized in collaboration with Merck & Co., Inc.,
known as MSD outside the US and Canada.
AstraZeneca is advancing multiple modalities that provide
complementary mechanisms for targeting Claudin 18.2, a promising
therapeutic target in gastric cancer. These include AZD0901, a
potential first-in-class antibody drug conjugate licensed from KYM
Biosciences Inc., currently in Phase III development, AZD5863, a
novel Claudin 18.2/CD3 T-cell engager bispecific antibody licensed
from Harbour Biomed in Phase I development, and AZD6422, an armored
autologous chimeric antigen receptor T cell (CAR-T) therapy,
currently being evaluated in an Investigator Initiated Trial (IIT)
in collaboration with AbelZeta in China.
In early development, AstraZeneca is developing two Glypican 3
(GPC3) armored CAR-Ts in HCC. AZD5851, currently in Phase I
development, is being developed globally, and C-CAR031 / AZD7003 is
being co-developed with AbelZeta in China where it is under
evaluation in an IIT.
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
- World Health Organization. Liver Cancer Fact Sheet. Available
at:
https://gco.iarc.who.int/media/globocan/factsheets/cancers/11-liver-and-intrahepatic-bile-ducts-fact-sheet.pdf.
Accessed September 2024.
- Liu Y, et al. Changes in the Epidemiology of Hepatocellular
Carcinoma in Asia. Cancers (Basel). 2022;14(18):4473.
- Tarao K, et al. Real impact of liver cirrhosis on the
development of hepatocellular carcinoma in various liver
diseases—meta‐analytic assessment. Cancer Med.
2019;8(3):1054-1065.
- Sayiner M, et al. Disease Burden of Hepatocellular Carcinoma: A
Global Perspective. Digestive Diseases and Sciences. 2019;64:
910-917.
- Colagrande S, et al. Challenges of advanced hepatocellular
carcinoma. World J Gastroenterol. 2016;22(34):7645-7659.
- World Health Organization. Cancer factsheets: Digestive organs
(oesophagus, anus, stomach, colon, rectum, liver and intrahepatic
bile ducts, pancreas, gallbladder). Available at:
https://gco.iarc.fr/today/en/fact-sheets-cancers. Accessed
September 2024.
US-93784 Last Updated 9/24
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version on businesswire.com: https://www.businesswire.com/news/home/20240916766941/en/
Media Inquiries
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