TROPION-Lung01, evaluating AstraZeneca and
Daiichi Sankyo’s datopotamab deruxtecan versus chemotherapy,
previously met the dual primary endpoint of progression-free
survival in the overall trial population
Presidential Symposium for NeoCOAST-2
demonstrates potential for datopotamab deruxtecan plus IMFINZI®
(durvalumab) and chemotherapy in neoadjuvant early-stage non-small
cell lung cancer
Detailed results from the TROPION-Lung01 Phase III trial showed
a clinically meaningful trend toward improving overall survival
(OS) with datopotamab deruxtecan (Dato-DXd) compared to docetaxel,
the current standard of care chemotherapy, in adult patients with
locally advanced or metastatic nonsquamous non-small cell lung
cancer (NSCLC) treated with at least one prior line of therapy.
These results will be presented today during an oral
presentation (OA08.03) at the IASLC 2024 World Conference on Lung
Cancer (WCLC) hosted by the International Association for the Study
of Lung Cancer.
Datopotamab deruxtecan is a specifically engineered
TROP2-directed DXd antibody drug conjugate discovered by Daiichi
Sankyo and being jointly developed by AstraZeneca and Daiichi
Sankyo.
In the overall trial population, OS results numerically favored
datopotamab deruxtecan compared to docetaxel (12.9 vs. 11.8 months)
but did not reach statistical significance (hazard ratio [HR] 0.94;
95% confidence interval [CI] 0.78-1.14; p=0.530). In the
prespecified subgroup of patients with nonsquamous NSCLC,
datopotamab deruxtecan showed a 2.3-month improvement in OS
compared to docetaxel (14.6 vs. 12.3 months; HR 0.84; 95% CI
0.68-1.05). In patients with nonsquamous NSCLC, OS improvement was
observed regardless of the presence of actionable genomic
alterations. In patients with squamous NSCLC, consistent with the
previous analysis, datopotamab deruxtecan did not show an OS
improvement.
Jacob Sands, MD, Dana-Farber Cancer Institute, Medical Oncology
and investigator in the trial, said: “Despite many efforts to
surpass docetaxel with novel approaches in previously treated
advanced or metastatic non-small cell lung cancer, patients only
survive for about one year. For datopotamab deruxtecan to show a
statistically significant improvement in progression-free survival
along with improved response rate, duration of response and an
overall survival improvement numerically consistent with
progression-free survival is clinically meaningful for patients
with nonsquamous lung cancer.”
Susan Galbraith, Executive Vice President, Oncology R&D,
AstraZeneca, said: “TROPION-Lung01 showed a clinically meaningful
trend towards improving the survival of patients with advanced or
metastatic nonsquamous non-small cell lung cancer, building on the
previously reported progression-free survival data. Together with
the data we have presented for the potential TROP2-QCS biomarker
and from NeoCOAST-2 in early-stage disease, these results
underscore our confidence in the important role datopotamab
deruxtecan can play across segments and settings of non-small cell
lung cancer.”
Ken Takeshita, MD, Global Head, R&D, Daiichi Sankyo, said:
“For patients with nonsquamous non-small cell lung cancer, disease
progression is common, making this patient population difficult to
treat. The data from TROPION-Lung01 demonstrate the potential of
datopotamab deruxtecan in this setting and support our
comprehensive development program where we are also evaluating this
TROP2-directed antibody drug conjugate as part of combination
strategies in earlier treatment settings of non-small cell lung
cancer.”
The safety profile of datopotamab deruxtecan in TROPION-Lung01
was consistent with the previous analysis including lower rates of
dose reduction (20%, 30%) and discontinuation (8%, 12%) due to
adverse events compared to docetaxel. The median treatment duration
for datopotamab deruxtecan was 4.2 months versus 2.8 months for
docetaxel. Grade 3 or higher treatment-related adverse events
(TRAEs) occurred in 26% and 42% of patients in the datopotamab
deruxtecan and docetaxel arms, respectively. The most common Grade
3 or higher TRAEs were neutropenia (1%, 23%), leukopenia (0%, 13%),
stomatitis (7%, 1%), anemia (4%, 4%), interstitial lung disease
(ILD) (4%, 1%) and asthenia (3%, 2%). No new ILD events of any
grade were adjudicated as drug-related since the previous
analysis.
In TROPION-Lung01, patient enrollment by tumor histology was
balanced across treatment arms and consistent with real world
incidence with approximately 75% of enrolled patients having
nonsquamous NSCLC.1,2 In both arms, 17% of patients had tumors
expressing actionable genomic alterations, such as epidermal growth
factor receptor (EGFR) mutations.
This final analysis of OS builds on the positive
progression-free survival (PFS) results presented at the 2023
European Society for Medical Oncology Congress, which showed
datopotamab deruxtecan demonstrated a statistically significant
improvement in PFS in the overall trial population and a clinically
meaningful PFS benefit in patients with nonsquamous NSCLC. The OS
data have been shared with health authorities currently reviewing
applications for this indication.
Summary of TROPION-Lung01 survival results
Overall trial population
Datopotamab
deruxtecan (n=299)
Docetaxel
(n=305)
Median OS (95% CI)i
12.9 months (11.0-13.9)
11.8 months (10.0-12.8)
HR (95% CI)
0.94 (0.78-1.14)
p-value
0.530
Pre-specified boundary (2-sided)
0.045
Nonsquamous histology
Datopotamab
deruxtecan (n=234)
Docetaxel
(n=234)
Median OS (95% CI)i
14.6 months (12.4-16.0)
12.3 months (10.7-14.0)
HR (95% CI)
0.84 (0.68-1.05)
OS probability at 12 months (95% CI)
58.8% (52.0-64.9)
52.8% (45.9-59.2)
OS probability at 24 months (95% CI)
29.0% (22.8-35.5)
21.7% (16.0-28.0)
Nonsquamous histology – with actionable
genomic alterations
Datopotamab
deruxtecan (n=48)
Docetaxel
(n=50)
Median OS (95% CI)i
15.6 months
9.8 months
HR (95% CI)
0.65 (0.40-1.08)
Nonsquamous histology – without
actionable genomic alterations
Datopotamab
deruxtecan (n=186)
Docetaxel
(n=184)
Median OS (95% CI)i
13.6 months
12.3 months
HR (95% CI)
0.89 (0.70-1.13)
CI, confidence interval; HR, hazard ratio;
OS, overall survival iMedian follow-up was 23.1 months for both the
datopotamab deruxtecan and docetaxel arms
Datopotamab deruxtecan plus IMFINZI® (durvalumab) and
chemotherapy showed promising response rates in patients with
early-stage resectable NSCLC
Results from the NeoCOAST-2 Phase II platform trial evaluating
IMFINZI® (durvalumab) in multiple novel combinations, before and
after surgery, in patients with early-stage (Stage IIA–IIIB)
resectable NSCLC were featured in a WCLC Presidential Symposium
(PL02.07). Preliminary results from the trial arm testing
neoadjuvant IMFINZI plus datopotamab deruxtecan and carboplatin
demonstrated a pathological complete response (pCR) rate of 34.1%
(95% CI 20.5-49.9) and a major pathological response (mPR) rate of
65.9% (95% CI 50.1-79.5). This was numerically higher than the
response rates shown by other combination regimens tested, however,
the trial was not powered to make direct statistical comparisons
between arms.
The safety profile of IMFINZI plus datopotamab deruxtecan and
carboplatin was consistent with the known safety profiles of these
agents. Surgical rates across arms were comparable and in line with
those shown in recent Phase III trials. AstraZeneca and Daiichi
Sankyo are evaluating datopotamab deruxtecan in combination with
IMFINZI in multiple ongoing trials.
Also featured in a WCLC Presidential Symposium were results from
an exploratory analysis of TROPION-Lung01 which showed TROP2 as
measured by AstraZeneca’s proprietary computational pathology
platform, quantitative continuous scoring (QCS), was predictive of
clinical outcomes in patients with advanced or metastatic NSCLC
treated with datopotamab deruxtecan.
IMPORTANT SAFETY INFORMATION FOR IMFINZI® and IMJUDO®
(tremelimumab-actl)
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.
- 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.
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 IMJUDO in combination with durvalumab,
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.
Notes
Advanced non-small cell lung cancer Nearly 2.5 million
lung cancer cases were diagnosed globally in 2022.1 NSCLC is the
most common type of lung cancer, accounting for about 80% of
cases.2 Approximately 75% and 25% of NSCLC tumors are of
nonsquamous or squamous histology, respectively.3 While
immunotherapy and targeted therapies have improved outcomes in the
1st-line metastatic setting, most patients eventually experience
disease progression and receive chemotherapy.4-6 For decades,
chemotherapy has been the last treatment available for patients
with advanced NSCLC, despite limited effectiveness and known side
effects.4-6
TROP2 is a protein broadly expressed in the majority of NSCLC
tumors.7 There is currently no TROP2-directed ADC approved for the
treatment of lung cancer.8,9
TROPION-Lung01 TROPION-Lung01 is a global, randomized,
multicenter, open-label Phase III trial evaluating the efficacy and
safety of datopotamab deruxtecan (6.0mg/kg) versus docetaxel
(75mg/m2) in adult patients with locally advanced or metastatic
NSCLC with and without actionable genomic alterations who require
systemic therapy following prior treatment. Patients with
actionable genomic alterations were previously treated with
platinum-based chemotherapy and an approved targeted therapy.
Patients without known actionable genomic alterations were
previously treated, concurrently or sequentially, with
platinum-based chemotherapy and a PD-1 or PD-L1 inhibitor.
The dual primary endpoints of TROPION-Lung01 are PFS as assessed
by blinded independent central review (BICR) and OS. Key secondary
endpoints include investigator-assessed PFS, objective response
rate (ORR), duration of response, time to response, disease control
rate as assessed by both BICR and investigator, and safety.
TROPION-Lung01 enrolled approximately 600 patients in Asia,
Europe, North America, Oceania and South America. For more
information visit ClinicalTrials.gov.
NeoCOAST-2 NeoCOAST-2 is a global, randomized,
multicenter, open-label, multi-arm Phase II platform trial
evaluating the efficacy and safety of IMFINZI® (durvalumab) in
multiple novel combinations, before and after surgery, in patients
with resectable, early-stage (Stage II-IIIB) NSCLC.
The dual primary endpoints of NeoCOAST-2 are antitumor activity
of neoadjuvant treatment assessed by pCR and the safety and
tolerability of neoadjuvant and adjuvant treatment. Key secondary
endpoints include event-free survival, disease-free survival and
ORR as assessed by both RECIST version 1.1 and investigator, OS,
tumor resection and mPR as defined by central blinded independent
pathologist review.
NeoCOAST-2 will enroll approximately 490 patients in Asia,
Europe and North America. For more information visit
ClinicalTrials.gov.
Datopotamab deruxtecan (Dato-DXd) Datopotamab deruxtecan
(Dato-DXd) is an investigational TROP2-directed ADC. Designed using
Daiichi Sankyo’s proprietary DXd ADC Technology, datopotamab
deruxtecan is one of six DXd ADCs in the oncology pipeline of
Daiichi Sankyo, and one of the most advanced programs in
AstraZeneca’s ADC scientific platform. Datopotamab deruxtecan is
comprised of a humanized anti-TROP2 IgG1 monoclonal antibody,
developed in collaboration with Sapporo Medical University,
attached to a number of topoisomerase I inhibitor payloads (an
exatecan derivative, DXd) via tetrapeptide-based cleavable
linkers.
A comprehensive global clinical development program is underway
with more than 20 trials evaluating the efficacy and safety of
datopotamab deruxtecan across multiple cancers, including NSCLC,
triple-negative breast cancer and HR-positive, HER2-negative breast
cancer. The program includes seven Phase III trials in lung cancer
and five Phase III trials in breast cancer evaluating datopotamab
deruxtecan as a monotherapy and in combination with other
anticancer treatments in various settings.
Daiichi Sankyo collaboration AstraZeneca and Daiichi
Sankyo entered into a global collaboration to jointly develop and
commercialize fam-trastuzumab deruxtecan-nxki in March 2019 and
datopotamab deruxtecan in July 2020, except in Japan where Daiichi
Sankyo maintains exclusive rights for each ADC. Daiichi Sankyo is
responsible for the manufacturing and supply of fam-trastuzumab
deruxtecan-nxki and datopotamab deruxtecan.
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 tremelimumab-actl;
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 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.
About 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 the us on social media
@AstraZeneca.
References
- World Health Organization. Global Cancer Observatory: Lung.
Available at:
https://gco.iarc.who.int/media/globocan/factsheets/cancers/15-trachea-bronchus-and-lung-fact-sheet.pdf.
Accessed September 2024.
- Cancer.net. Lung Cancer – Non-Small Cell: Statistics. Available
at:
https://www.cancer.net/cancer-types/lung-cancer-non-small-cell/statistics#:~:text=NSCLC%20is%20the%20most%20common,be%20diagnosed%20with%20lung%20cancer.
Accessed September 2024.
- National Cancer Institute. SEER Cancer Statistics Factsheets:
Lung and Bronchus Cancer. Available at:
https://seer.cancer.gov/archive/csr/1975_2017/results_merged/sect_15_lung_bronchus.pdf.
Accessed September 2024.
- Chen R, et al. Emerging therapeutic agents for advanced
non-small cell lung cancer. J Hematol Oncol. 2020;13(1):58.
- Majeed U, et al. Targeted therapy in advanced non-small cell
lung cancer: current advances and future trends. J Hematol Oncol.
2021;14(1):108.
- Pircher, A, et al. Docetaxel in the Treatment of Non-small Cell
Lung Cancer (NSCLC) – An Observational Study Focusing on Symptom
Improvement. Anticancer Research. 2013;33(9):3831-3836.
- Mito R, et al. Clinical impact of TROP2 in non‐small lung
cancers and its correlation with abnormal p53 nuclear accumulation.
Pathol Int. 2020;70(5):287-294.
- Rodríguez-Abreau D, et al. Pemetrexed plus platinum with or
without pembrolizumab in patients with previously untreated
metastatic nonsquamous NSCLC: protocol-specified final analysis
from KEYNOTE-189. Ann Onc. 2021 Jul;32(7): 881-895.
- American Cancer Society. Targeted Drug Therapy for Non-Small
Cell Lung Cancer. Available at:
https://www.cancer.org/cancer/types/lung-cancer/treating-non-small-cell/targeted-therapies.html.
Accessed September 2024.
US-93338 Last Updated 9/24
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Media Inquiries Brendan McEvoy +1 302 885 2677 Chelsea
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