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AstraZeneca Heads to 2018 ASCO Annual Meeting with Its Diversified Oncology Portfolio and Next-Generation Pipeline

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91 accepted abstracts at ASCO, including LYNPARZA®
(olaparib) in prostate cancer and moxetumomab pasudotox in hairy cell
leukemia

AstraZeneca and MedImmune, its global biologics research and development
arm, head to the 2018 American Society of Clinical Oncology (ASCO)
Annual Meeting in Chicago, IL, June 1-5, 2018, with an expanded
portfolio in Oncology.

Having achieved 16 regulatory approvals across major markets (US, EU,
Japan and China), AstraZeneca will be sharing its R&D momentum at ASCO
with seven "Best of ASCO" presentations and 14 oral presentations from a
total of 91 accepted abstracts. These presentations will showcase
AstraZeneca's four scientific platforms: Immuno-Oncology (IO), DNA
Damage Response (DDR), Anti-Drug Conjugates (ADCs), and Tumor Drivers
and Resistance.

Dave Fredrickson, Executive Vice President, Head of Oncology Business
Unit said: "In just four years, AstraZeneca has launched four innovative
medicines to treat serious cancers: LYNPARZA in ovarian and metastatic
breast cancers, IMFINZI in bladder cancer and unresectable stage III
non-small cell lung cancer, TAGRISSO in epidermal growth factor
receptor-mutated non-small cell lung cancer and CALQUENCE as the first
hematology medicine in mantle cell lymphoma. At this year's ASCO
meeting, the Company will showcase a strong portfolio, a rich pipeline
and a focus on impactful industry partnerships which will fuel continued
advances in oncology and hematology."

LYNPARZA® (olaparib): Study 08 data in
prostate cancer

An oral presentation of Study 08, evaluating olaparib in combination
with abiraterone in metastatic castration-resistant prostate cancer,
will highlight the potential of poly (ADP-ribose) polymerase (PARP)
inhibition beyond ovarian and metastatic breast cancers, regardless of
homologous recombination repair mutation status (Abstract #5003).
Olaparib is being jointly developed and commercialized by AstraZeneca
and MSD, known as Merck in the US and Canada.

Progress in hematology

Response rates and safety data from the Phase III (‘1053') multicenter
trial of moxetumomab pasudotox, an investigational agent that is part of
our ADC platform, in relapsed or refractory hairy cell leukemia (HCL)
patients (Abstract #7004) will be presented. The FDA has granted the
moxetumomab pasudotox Biologics License Application Priority Review
status; if approved, it will be a first-in-class treatment for patients
with relapsed refractory HCL.

New investigational data will also be presented for CALQUENCE®
(acalabrutinib), a selective Bruton's tyrosine kinase (BTK)
inhibitor and AstraZeneca's first medicine approved in hematology.
Findings will be shared in an oral presentation of the Phase II clinical
trial (WM-001) of patients with treatment-naïve, relapsed or refractory
Waldenström macroglobulinemia (Abstract #7501).

Investigator-led studies highlight the value of collaboration in new
areas of unmet need

AstraZeneca's broad network of industry and academic partners is
broadening exploration of the Company's pipeline into additional tumor
types where unmet patient needs remain. The US National Cancer Institute
(NCI), a division of the US National Institutes of Health (NIH), will
present Phase II data from the ongoing SPRINT trial evaluating MEK 1/2
inhibitor selumetinib (AZD6244, ARRY-142886), a potential new medicine
within the AstraZeneca and MSD partnership, in pediatric patients with
neurofibromatosis type 1 (NF1) and plexiform neurofibromas (Abstract
#10503). The SPRINT abstract was awarded the 2018 Conquer Cancer
Foundation of ASCO/Bradley Stuart Beller Special Merit Award.

Additional investigator-sponsored research includes a late-breaking oral
presentation on the Phase II GeparNuevo trial of neoadjuvant treatment
with IMFINZI® (durvalumab) in triple-negative breast cancer
(TNBC). AstraZeneca initiated this study alongside the German Breast
Group and Celgene (Abstract #104), and the DREAM Phase II trial of
durvalumab in combination with chemotherapy in first-line mesothelioma
(Abstract #8503).

Early pipeline powered by combinations

AstraZeneca's early-stage pipeline will also be showcased at the 2018
ASCO Annual Meeting with 39 abstracts highlighting its breadth and depth.

In an oral presentation, data from PAKT, a Phase II trial of
capivasertib (AZD5363), a highly selective, oral, AKT inhibitor with
paclitaxel, demonstrate the impact of this combination on progression
free survival and overall survival in previously untreated, metastatic
TNBC (Abstract #1007). This trial was sponsored and led by Queen Mary
University London and the Bart's Cancer Institute.

Additionally, progress against PD(L)-1-insensitive tumors will be
highlighted with presentations of two first-in-human studies from the
early IO pipeline; the investigational anti-CD73 human monoclonal
antibody oleclumab alone or in combination with durvalumab in advanced
pancreatic cancer and colorectal cancer (Abstract #4123), and
monalizumab (NKG2A) in combination with durvalumab in patients with
metastatic microsatellite-stable colorectal cancer (Abstract #3540).

Key AstraZeneca/MedImmune presentations at ASCO 2018

Lead author

 

Abstract title

 

Presentation details

DNA Damage Response

 
Clarke N   Olaparib combined with abiraterone in patients (pts) with metastatic
castration-resistant prostate cancer (mCRPC): A randomized Phase II
trial
  Oral

Genitourinary (Prostate) Cancer

Monday June 4th, 3:00-6:00

Presentation Time: 4:00-4:12

Location: Hall D1

Abstract #5003

Westin SN   Phase I trial of olaparib (PARP inhibitor) and vistusertib (mTORC
1/2 inhibitor) in recurrent endometrial, ovarian and triple negative
breast cancer
  Oral

Gynecologic Cancer

Tuesday June 5th, 10:57-11:09

Location: S100a

Abstract #5504

Johnson M   A Phase I, open-label, multicenter dose escalation study to assess
the safety, tolerability, and pharmacokinetics of AZD2811
nanoparticle in patients with advanced solid tumors
  Poster

Developmental Therapeutics – Clinical Pharmacology and
Experimental Therapeutics

Monday June 4th, 08:00-11:30

Abstract #2592

Poster #418

Heymach J   An open-label, multidrug, biomarker-directed, multicenter phase II
umbrella study in patients with non-small cell lung cancer, who
progressed on an anti-PD-1/PD-L1 containing therapy (HUDSON)
  Poster

Developmental Therapeutics – Immunotherapy

Monday June 4th, 08:00-11:30

Location: Hall A

Abstract #TPS3120

Poster #324b

 

Immuno-Oncology

Loibl S   Randomized Phase II neoadjuvant study (GeparNuevo) to investigate
the addition of durvalumab to a taxane-anthracycline containing
chemotherapy in triple-negative breast cancer (TNBC)
  Oral

Compelling Combinations: Raising the Bar With Immunotherapy

Sunday June 3rd, 09:45-11:15

Presentation Time: 09:57-10:09

Location: Hall D1

Abstract #104

Nowak AK   DREAM: A Phase II study of durvalumab with first line chemotherapy
in mesothelioma—First results
  Oral

Lung Cancer—Non-Small Cell Local-Regional/Small Cell/Other
Thoracic Cancers

Monday June 4th, 08:00-11:00

Presentation Time: 09:00-09:12

Location: Hall B1

Abstract #8503

Garassino MC   Durvalumab in ≥3rd-line advanced NSCLC: Updated results from the
Phase II ATLANTIC study
  Poster

Lung Cancer—Non-Small Cell Metastatic

Sunday June 3rd, 08:00-11:30

Location: Hall A

Abstract #9058

Poster #381

Segal NH   First-in-human dose escalation of monalizumab plus durvalumab, with
expansion in patients with metastatic microsatellite-stable
colorectal cancer
  Poster

Gastrointestinal (Colorectal) Cancer

Sunday June 3rd, 08:00-11:30

Location: Hall A

Abstract #3540

Poster #33

Overman MJ   Safety, Efficacy and Pharmacodynamics (PD) of MEDI9447 (oleclumab)
Alone or in Combination with Durvalumab in Advanced Colorectal
Cancer (CRC) or Pancreatic Cancer (panc)
  Poster

Gastrointestinal (Noncolorectal) Cancer

Sunday June 3rd, 08:00-11:30

Location: Hall A

Abstract #4123

Poster #312

 

Tumor Drivers & Resistance

Gross AM   SPRINT: Phase II study of the MEK 1/2 inhibitor selumetinib
(AZD6244, ARRY-142886) in children with neurofibromatosis type 1
(NF1) and inoperable plexiform neurofibromas (PN)
  Oral

Pediatric Oncology I

Saturday June 2nd, 3:00-6:00

Presentation Time: 4:00-4:12

Location: S504

Abstract #10503

Owen R   Acalabrutinib in patients (pts) with Waldenström macroglobulinemia
(WM)
  Oral

Hematologic Malignancies—Lymphoma and Chronic Lymphocytic Leukemia

Sunday June 3rd, 09:45-12:45

Presentation Time: 09:57-10:09

Abstract #7501

Schmid P   AZD5363 plus paclitaxel versus placebo plus paclitaxel as first-line
therapy for metastatic triple-negative breast cancer (PAKT): A
randomized, double-blind, placebo-controlled, Phase II trial
  Oral

Breast Cancer—Metastatic

Sunday June 3rd, 08:00-11:00

Presentation Time: 10:12-10:24

Location: Hall D2

Abstract #1007

 

Antibody-Drug Conjugates

Kreitman RJ   Moxetumomab pasudotox in heavily pretreated patients with
relapsed/refractory hairy cell leukemia: Results of a pivotal
international study
  Oral

Hematologic Malignancies—Leukemia, Myelodysplastic Syndromes, and
Allotransplant

Saturday June 2nd, 3:00-6:00

Discussion Time: 4:12-4:24

Location: E450

Abstract #7004

LYNPARZA® (olaparib) Important Safety
Information

CONTRAINDICATIONS

There are no contraindications for LYNPARZA.

WARNINGS AND PRECAUTIONS

Myelodysplastic Syndrome/Acute Myeloid Leukemia (MDS/AML):
Occurred in <1.5% of patients exposed to LYNPARZA monotherapy, and the
majority of events had a fatal outcome. The duration of therapy in
patients who developed secondary MDS/AML varied from <6 months to >2
years. All of these patients had previous chemotherapy with platinum
agents and/or other DNA-damaging agents, including radiotherapy, and
some also had a history of more than one primary malignancy or of bone
marrow dysplasia.

Do not start LYNPARZA until patients have recovered from hematological
toxicity caused by previous chemotherapy (≤Grade 1). Monitor complete
blood count for cytopenia at baseline and monthly thereafter for
clinically significant changes during treatment. For prolonged
hematological toxicities, interrupt LYNPARZA and monitor blood count
weekly until recovery.

If the levels have not recovered to Grade 1 or less after 4 weeks, refer
the patient to a hematologist for further investigations, including bone
marrow analysis and blood sample for cytogenetics. Discontinue LYNPARZA
if MDS/AML is confirmed.

Pneumonitis: Occurred in <1% of patients exposed to LYNPARZA, and
some cases were fatal. If patients present with new or worsening
respiratory symptoms such as dyspnea, cough, and fever, or a
radiological abnormality occurs, interrupt LYNPARZA treatment and
initiate prompt investigation. Discontinue LYNPARZA if pneumonitis is
confirmed and treat patient appropriately.

Embryo-Fetal Toxicity: Based on its mechanism of action and
findings in animals, LYNPARZA can cause fetal harm. A pregnancy test is
recommended for females of reproductive potential prior to initiating
treatment.

Females

Advise females of reproductive potential of the potential risk to a
fetus and to use effective contraception during treatment and for 6
months following the last dose.

Males

Advise male patients with female partners of reproductive potential or
who are pregnant to use effective contraception during treatment and for
3 months following the last dose of LYNPARZA and to not donate sperm
during this time.

ADVERSE REACTIONS—Maintenance Setting

Most common adverse reactions (Grades 1-4) in ≥20% of patients in
clinical trials of LYNPARZA in the maintenance setting for SOLO-2:
nausea (76%), fatigue (including asthenia) (66%), anemia (44%), vomiting
(37%), nasopharyngitis/upper respiratory tract infection (URI)/influenza
(36%), diarrhea (33%), arthralgia/myalgia (30%), dysgeusia (27%),
headache (26%), decreased appetite (22%), and stomatitis (20%).

Study 19: nausea (71%), fatigue (including asthenia) (63%),
vomiting (35%), diarrhea (28%), anemia (23%), respiratory tract
infection (22%), constipation (22%), headache (21%), and decreased
appetite (21%).

Most common laboratory abnormalities (Grades 1-4) in ≥25% of patients in
clinical trials of LYNPARZA in the maintenance setting (SOLO-2/Study
19)
were: increase in mean corpuscular volume (89%/82%), decrease in
hemoglobin (83%/82%), decrease in leukocytes (69%/58%), decrease in
lymphocytes (67%/52%), decrease in absolute neutrophil count (51%/47%),
increase in serum creatinine (44%/45%), and decrease in platelets
(42%/36%).

ADVERSE REACTIONS—Advanced gBRCAm ovarian cancer

Most common adverse reactions (Grades 1-4) in ≥20% of patients in
clinical trials of LYNPARZA for advanced gBRCAm ovarian cancer after
3 or more lines of chemotherapy
(pooled from 6 studies) were:
fatigue (including asthenia) (66%), nausea (64%), vomiting (43%), anemia
(34%), diarrhea (31%), nasopharyngitis/upper respiratory tract infection
(URI) (26%), dyspepsia (25%), myalgia (22%), decreased appetite (22%),
and arthralgia/musculoskeletal pain (21%).

Most common laboratory abnormalities (Grades 1-4) in ≥25% of patients in
clinical trials of LYNPARZA for advanced gBRCAm ovarian cancer
(pooled from 6 studies) were: decrease in hemoglobin (90%), increase in
mean corpuscular volume (57%), decrease in lymphocytes (56%), increase
in serum creatinine (30%), decrease in platelets (30%), and decrease in
absolute neutrophil count (25%).

ADVERSE REACTIONS—gBRCAm, HER2-negative breast cancer

Most common adverse reactions (Grades 1-4) in ≥20% of patients in OlympiAD
were: nausea (58%), anemia (40%), fatigue (including asthenia) (37%),
vomiting (30%), neutropenia (27%), respiratory tract infection (27%),
leukopenia (25%), diarrhea (21%), and headache (20%).

Most common laboratory abnormalities (Grades 1-4) in ≥25% of patients in OlympiAD
were: decrease in hemoglobin (82%), decrease in lymphocytes (73%),
decrease in leukocytes (71%), increase in mean corpuscular volume (71%),
decrease in absolute neutrophil count (46%), and decrease in platelets
(33%).

DRUG INTERACTIONS

Anticancer Agents: Clinical studies of LYNPARZA in combination
with other myelosuppressive anticancer agents, including DNA-damaging
agents, indicate a potentiation and prolongation of myelosuppressive
toxicity.

CYP3A Inhibitors: Avoid concomitant use of strong or moderate
CYP3A inhibitors. If a strong or moderate CYP3A inhibitor must be
co-administered, reduce the dose of LYNPARZA. Advise patients to avoid
grapefruit, grapefruit juice, Seville oranges, and Seville orange juice
during LYNPARZA treatment.

CYP3A Inducers: Avoid concomitant use of strong or moderate CYP3A
inducers when using LYNPARZA. If a moderate inducer cannot be avoided,
there is a potential for decreased efficacy of LYNPARZA.

USE IN SPECIFIC POPULATIONS

Lactation: No data are available regarding the presence of
olaparib in human milk, its effects on the breastfed infant or on milk
production. Because of the potential for serious adverse reactions in
the breastfed infant, advise a lactating woman not to breastfeed during
treatment with LYNPARZA and for 1 month after receiving the final dose.

Pediatric Use: The safety and efficacy of LYNPARZA have not been
established in pediatric patients.

Hepatic Impairment: No adjustment to the starting dose is
required in patients with mild hepatic impairment (Child-Pugh
classification A). There are no data in patients with moderate or severe
hepatic impairment.

Renal Impairment: No adjustment to the starting dose is necessary
in patients with mild renal impairment (CLcr=51-80 mL/min). In patients
with moderate renal impairment (CLcr=31-50 mL/min), reduce the dose to
200 mg twice daily. There are no data in patients with severe renal
impairment or end-stage renal disease (CLcr ≤30 mL/min).

DOSING AND ADMINISTRATION

To avoid substitution errors and overdose, do not substitute LYNPARZA
tablets with LYNPARZA capsules
on a milligram-to-milligram basis due
to differences in the dosing and bioavailability of each formulation.
Recommended tablet dose is 300 mg, taken orally twice daily, with or
without food. Continue treatment until disease progression or
unacceptable toxicity. For adverse reactions, consider dose interruption
or dose reduction.

INDICATIONS

LYNPARZA is a poly (ADP-ribose) polymerase (PARP) inhibitor indicated:

For the maintenance treatment of adult patients with recurrent
epithelial ovarian, fallopian tube, or primary peritoneal cancer, who
are in complete or partial response to platinum-based chemotherapy.

For the treatment of adult patients with deleterious or suspected
deleterious germline BRCA-mutated (gBRCAm) advanced ovarian cancer who
have been treated with 3 or more prior lines of chemotherapy. Select
patients for therapy based on an FDA-approved companion diagnostic for
LYNPARZA.

In patients with deleterious or suspected deleterious gBRCAm, human
epidermal growth factor receptor 2 (HER2)-negative metastatic breast
cancer who have been treated with chemotherapy in the neoadjuvant,
adjuvant or metastatic setting. Patients with hormone receptor
(HR)-positive breast cancer should have been treated with a prior
endocrine therapy or be considered inappropriate for endocrine therapy.
Select patients for therapy based on an FDA-approved companion
diagnostic for LYNPARZA.

Please see complete Prescribing
Information
, including Patient Information (Medication Guide).

IMFINZI® (durvalumab) Important Safety
Information

There are no contraindications for IMFINZI® (durvalumab).

IMFINZI can cause serious, potentially fatal adverse reactions
including immune-mediated pneumonitis, hepatitis, colitis or diarrhea,
endocrinopathies, nephritis, rash or dermatitis,
other immune-mediated adverse reactions, infection, and infusion-related
reactions. Please refer to the full Prescribing Information for
important dosage modification and management information specific to
adverse reactions.

Immune-Mediated Pneumonitis

IMFINZI can cause immune-mediated pneumonitis, defined as requiring use
of corticosteroids. Fatal cases have been reported. Monitor patients for
signs and symptoms of pneumonitis and evaluate with radiographic imaging
when suspected. Administer corticosteroids for Grade 2 or greater
pneumonitis. Withhold IMFINZI for Grade 2 pneumonitis; permanently
discontinue for Grade 3 or 4 pneumonitis.

In clinical studies enrolling 1889 patients with various cancers who
received IMFINZI, pneumonitis occurred in 5% of patients, including
Grade 3 (0.8%), Grade 4 (<0.1%), and Grade 5 (0.3%) pneumonitis.
Pneumonitis led to discontinuation of IMFINZI in 1.5% of the 1889
patients. The incidence of pneumonitis (including radiation pneumonitis)
was higher in patients in the PACIFIC study who completed treatment with
definitive chemoradiation within 42 days prior to initiation of IMFINZI
(34%) compared to patients in other clinical studies (2.3%) in which
radiation therapy was generally not administered immediately prior to
initiation of IMFINZI. In the PACIFIC study, the incidence of Grade 3
pneumonitis was 3.4% and of Grade 5 pneumonitis was 1.1% in the IMFINZI
arm. In the PACIFIC study, pneumonitis led to discontinuation of IMFINZI
in 6% of patients.

Immune-Mediated Hepatitis

IMFINZI can cause immune-mediated hepatitis, defined as requiring use of
corticosteroids. Fatal cases have been reported. Monitor patients for
signs and symptoms of hepatitis during and after discontinuation of
IMFINZI, including clinical chemistry monitoring. Administer
corticosteroids for Grade 2 or higher elevations of ALT, AST, and/or
total bilirubin. Withhold IMFINZI for ALT or AST greater than 3 but less
than or equal to 8 times the ULN or total bilirubin greater than 1.5 but
less than or equal to 5 times the ULN; permanently discontinue IMFINZI
for ALT or AST greater than 8 times the ULN or total bilirubin greater
than 5 times the ULN or concurrent ALT or AST greater than 3 times the
ULN and total bilirubin greater than 2 times the ULN with no other cause.

In clinical studies enrolling 1889 patients with various cancers who
received IMFINZI, hepatitis occurred in 12% of patients, including Grade
3 (4.4%), Grade 4 (0.4%), and Grade 5 (0.2%) hepatitis. Hepatitis led to
discontinuation of IMFINZI in 0.7% of the 1889 patients.

Immune-Mediated Colitis

IMFINZI can cause immune-mediated colitis, defined as requiring use of
corticosteroids. Administer corticosteroids for Grade 2 or greater
colitis or diarrhea. Withhold IMFINZI for Grade 2 colitis or diarrhea;
permanently discontinue for Grade 3 or 4 colitis or diarrhea.

In clinical studies enrolling 1889 patients with various cancers who
received IMFINZI, colitis or diarrhea occurred in 18% of patients,
including Grade 3 (1.0%) and Grade 4 (0.1%) colitis. Diarrhea or colitis
led to discontinuation of IMFINZI in 0.4% of the 1889 patients.

Immune-Mediated Endocrinopathies

IMFINZI can cause immune-mediated endocrinopathies, including thyroid
disorders, adrenal insufficiency, type 1 diabetes mellitus, and
hypophysitis/hypopituitarism. Monitor patients for clinical signs
and symptoms of endocrinopathies.

  • Thyroid disorders—Monitor thyroid function prior to and
    periodically during treatment. Initiate hormone replacement therapy or
    medical management of hyperthyroidism as clinically indicated.
    Withhold IMFINZI for Grades 2–4 hyperthyroidism, until clinically
    stable. Continue IMFINZI for hypothyroidism.

In clinical studies enrolling 1889 patients with various cancers who
received IMFINZI, hypothyroidism occurred in 11% of patients, while
hyperthyroidism occurred in 7% of patients. Thyroiditis occurred in 0.9%
of patients, including Grade 3 (<0.1%). Hypothyroidism was preceded by
thyroiditis or hyperthyroidism in 25% of patients.

  • Adrenal insufficiency—Administer corticosteroids as clinically
    indicated and withhold IMFINZI until clinically stable for Grade 2 or
    higher adrenal insufficiency. In clinical studies enrolling 1889
    patients with various cancers who received IMFINZI, adrenal
    insufficiency occurred in 0.7% of patients, including Grade 3 (<0.1%)
    adrenal insufficiency.
  • Type 1 diabetes mellitus—Initiate treatment with insulin as
    clinically indicated. Withhold IMFINZI for Grades 2–4 type 1 diabetes
    mellitus, until clinically stable. In clinical studies enrolling 1889
    patients with various cancers who received IMFINZI, type 1 diabetes
    mellitus occurred in <0.1% of patients.
  • Hypophysitis—Administer corticosteroids and hormone replacement
    as clinically indicated and withhold IMFINZI until clinically stable
    for Grade 2 or higher hypophysitis. Hypopituitarism leading to adrenal
    insufficiency and diabetes insipidus occurred in <0.1% of 1889
    patients with various cancers who received IMFINZI.

Immune-Mediated Nephritis

IMFINZI can cause immune-mediated nephritis, defined as evidence of
renal dysfunction requiring use of corticosteroids. Fatal cases have
occurred. Monitor patients for abnormal renal function tests prior to
and periodically during treatment with IMFINZI. Administer
corticosteroids as clinically indicated. Withhold IMFINZI for creatinine
greater than 1.5 to 3 times the ULN; permanently discontinue IMFINZI and
administer corticosteroids in patients with creatinine greater than 3
times the ULN.

In clinical studies enrolling 1889 patients with various cancers who
received IMFINZI, nephritis (reported as any of the following: increased
creatinine or urea, acute kidney injury, renal failure, decreased
glomerular filtration rate, tubulointerstitial nephritis, decreased
creatinine clearance, glomerulonephritis, and nephritis) occurred in
6.3% of the patients including Grade 3 (1.1%), Grade 4 (0.2%), and Grade
5 (0.1%) nephritis. IMFINZI was discontinued in 0.3% of the 1889
patients.

Immune-Mediated Dermatologic Reactions

IMFINZI can cause immune-mediated rash. Bullous dermatitis and Stevens
Johnson Syndrome (SJS)/toxic epidermal necrolysis (TEN) have occurred
with other products in this class. Administer corticosteroids for Grade
2 rash or dermatitis lasting for more than 1 week or for Grade 3 or 4
rash or dermatitis. Withhold IMFINZI for Grade 2 rash or dermatitis
lasting longer than 1 week or Grade 3 rash or dermatitis; permanently
discontinue IMFINZI in patients with Grade 4 rash or dermatitis.

In clinical studies enrolling 1889 patients with various cancers who
received IMFINZI, 26% of patients developed rash or dermatitis and 0.4%
of the patients developed vitiligo. Rash or dermatitis led to
discontinuation of IMFINZI in 0.1% of the 1889 patients.

Other Immune-Mediated Adverse Reactions

IMFINZI can cause severe and fatal immune-mediated adverse reactions.
These immune-mediated reactions may involve any organ system. While
immune-mediated reactions usually manifest during treatment with
IMFINZI, immune-mediated adverse reactions can also manifest after
discontinuation of IMFINZI. For suspected immune-mediated adverse
reactions, exclude other causes and initiate corticosteroids as
clinically indicated. Withhold IMFINZI for Grade 3 immune-mediated
adverse reactions, unless clinical judgment indicates discontinuation;
permanently discontinue IMFINZI for Grade 4 adverse reactions.

The following clinically significant, immune-mediated adverse reactions
occurred at an incidence of less than 1% each in 1889 patients who
received IMFINZI: aseptic meningitis, hemolytic anemia, immune
thrombocytopenic purpura, myocarditis, myositis, and ocular inflammatory
toxicity, including uveitis and keratitis. Additional clinically
significant immune-mediated adverse reactions have been seen with other
products in this class (see Warnings and Precautions Section 5.7 of
IMFINZI full Prescribing Information).

Infection

IMFINZI can cause serious infections, including fatal cases. Monitor
patients for signs and symptoms of infection and treat as clinically
indicated. Withhold IMFINZI for Grade 3 or 4 infection, until clinically
stable.

In clinical studies enrolling 1889 patients with various cancers who
received IMFINZI, infections occurred in 43% of patients, including
Grade 3 (8%), Grade 4 (1.9%), and Grade 5 (1.0%). The overall incidence
of infections in IMFINZI-treated patients in the PACIFIC study (56%) was
higher compared to patients in other clinical studies (38%) in which
radiation therapy was generally not administered immediately prior to
initiation of IMFINZI. In patients with UC in Study 1108 (n=182), the
most common Grade 3 or higher infection was urinary tract infections,
which occurred in 4% of patients. In patients with Stage III NSCLC in
the PACIFIC study, the most common Grade 3 or higher infection was
pneumonia, which occurred in 5% of patients.

Infusion-Related Reactions

IMFINZI can cause severe or life-threatening infusion-related reactions.
Monitor patients for signs and symptoms of an infusion-related reaction.
Interrupt or slow the rate of infusion for Grades 1–2 infusion-related
reactions; permanently discontinue for Grades 3–4 infusion-related
reactions.

In clinical studies enrolling 1889 patients with various cancers who
received IMFINZI, infusion-related reactions occurred in 2.2% of
patients, including Grade 3 (0.3%).

Embryo-Fetal Toxicity

Based on its mechanism of action and data from animal studies, IMFINZI
can cause fetal harm when administered to a pregnant woman. There are no
data on the use of IMFINZI in pregnant women. Advise pregnant women of
the potential risk to a fetus and advise women of reproductive potential
to use effective contraception during treatment and for at least 3
months after the last dose of IMFINZI.

Lactation

There is no information regarding the presence of IMFINZI in human milk;
however, because of the potential for adverse reactions in breastfed
infants from IMFINZI, advise women not to breastfeed during treatment
and for at least 3 months after the last dose.

Most Common Adverse Reactions

  • In patients with UC in Study 1108 (n=182), the most common adverse
    reactions (≥15%) were fatigue (39%), musculoskeletal pain (24%),
    constipation (21%), decreased appetite (19%), nausea (16%), peripheral
    edema (15%), and urinary tract infection (15%). The most common Grade
    3 or 4 adverse reactions (≥3%) were fatigue, urinary tract infection,
    musculoskeletal pain, abdominal pain, dehydration, and general
    physical health deterioration.
  • In patients with UC in Study 1108, discontinuation due to adverse
    reactions occurred in 3.3% of patients. Serious adverse reactions
    occurred in 46% of patients. The most frequent serious adverse
    reactions (>2%) were acute kidney injury (4.9%), urinary tract
    infection (4.4%), musculoskeletal pain (4.4%), liver injury (3.3%),
    general physical health deterioration (3.3%), sepsis, abdominal pain,
    and pyrexia/tumor associated fever (2.7% each).
  • In patients with Stage III NSCLC in the PACIFIC study (IMFINZI n=475),
    the most common adverse reactions (≥20% of patients) 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 reaction (≥3%) was pneumonia (7%).
  • In patients with Stage III NSCLC in the PACIFIC study (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% of patients) 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.

The safety and effectiveness of IMFINZI have not been established in
pediatric patients.

Indications

IMFINZI is indicated for the treatment of patients with locally advanced
or metastatic urothelial carcinoma who:

  • have disease progression during or
    following platinum-containing chemotherapy.
  • have disease progression within 12 months of neoadjuvant or adjuvant
    treatment with platinum-containing chemotherapy.

This indication is approved under accelerated approval based on tumor
response rate and duration of response. Continued approval for this
indication may be contingent upon verification and description of
clinical benefit in confirmatory trials.

IMFINZI is indicated for the treatment of patients with unresectable
Stage III non-small cell lung cancer (NSCLC) whose disease has not
progressed following concurrent platinum-based chemotherapy and
radiation therapy.

Please see complete Prescribing
Information
, including Medication Guide.

TAGRISSO® (osimertinib) Important Safety
Information

  • There are no contraindications for TAGRISSO
  • Interstitial lung disease (ILD)/pneumonitis occurred in 3.9% of the
    1142 TAGRISSO-treated patients; 0.4% of cases were fatal. Withhold
    TAGRISSO and promptly investigate for ILD in patients who present with
    worsening of respiratory symptoms which may be indicative of ILD (eg,
    dyspnea, cough and fever). Permanently discontinue TAGRISSO if ILD is
    confirmed
  • Heart rate-corrected QT (QTc) interval prolongation occurred in
    TAGRISSO-treated patients. Of the 1142 TAGRISSO-treated patients in
    clinical trials, 0.9% were found to have a QTc > 500 msec, and 3.6% of
    patients had an increase from baseline QTc > 60 msec. No QTc-related
    arrhythmias were reported. Conduct periodic monitoring with ECGs and
    electrolytes in patients with congenital long QTc syndrome, congestive
    heart failure, electrolyte abnormalities, or those who are taking
    medications known to prolong the QTc interval. Permanently discontinue
    TAGRISSO in patients who develop QTc interval prolongation with
    signs/symptoms of life-threatening arrhythmia
  • Cardiomyopathy occurred in 2.6% of the 1142 TAGRISSO-treated patients;
    0.1% of cardiomyopathy cases were fatal. A decline in left ventricular
    ejection fraction (LVEF) ≥10% from baseline and to <50% LVEF occurred
    in 3.9% of 908 patients who had baseline and at least one follow-up
    LVEF assessment. Conduct cardiac monitoring, including
    assessment of LVEF at baseline and during treatment, in patients with
    cardiac risk factors. Assess LVEF in patients who develop relevant
    cardiac signs or symptoms during treatment. For symptomatic congestive
    heart failure, permanently discontinue TAGRISSO
  • Keratitis was reported in 0.7% of 1142 patients treated with TAGRISSO
    in clinical trials. Promptly refer patients with signs and symptoms
    suggestive of keratitis (such as eye inflammation, lacrimation, light
    sensitivity, blurred vision, eye pain and/or red eye) to an
    ophthalmologist
  • Verify pregnancy status of females of reproductive potential prior to
    initiating TAGRISSO. Advise pregnant women of the potential risk to a
    fetus. Advise females of reproductive potential to use effective
    contraception during treatment with TAGRISSO and for 6 weeks after the
    final dose. Advise males with female partners of reproductive
    potential to use effective contraception for 4 months after the final
    dose
  • Most common adverse reactions (≥20%) were diarrhea, rash, dry skin,
    nail toxicity, stomatitis, fatigue and decreased appetite

INDICATIONS

  • TAGRISSO is indicated for the first-line treatment of patients with
    metastatic non-small cell lung cancer (NSCLC) whose tumors have
    epidermal growth factor receptor (EGFR) exon 19 deletions or exon 21
    L858R mutations, as detected by an FDA-approved test
  • TAGRISSO is indicated for the treatment of patients with metastatic
    EGFR T790M mutation-positive NSCLC, as detected by an FDA-approved
    test, whose disease has progressed on or after EGFR tyrosine kinase
    inhibitor (TKI) therapy

Please see complete Prescribing
Information
 including Patient Information.

CALQUENCE® (acalabrutinib) Important Safety
Information

Hemorrhage

Serious hemorrhagic events, including fatal events, have occurred in the
combined safety database of 612 patients with hematologic malignancies
treated with CALQUENCE monotherapy. Grade 3 or higher bleeding events,
including gastrointestinal, intracranial, and epistaxis, have been
reported in 2% of patients. Overall, bleeding events, including bruising
and petechiae of any grade, occurred in approximately 50% of patients
with hematological malignancies.

The mechanism for the bleeding events is not well understood.

CALQUENCE may further increase the risk of hemorrhage in patients
receiving antiplatelet or anticoagulant therapies, and patients should
be monitored for signs of bleeding.

Consider the benefit-risk of withholding CALQUENCE for 3 to 7 days pre-
and post-surgery, depending upon the type of surgery and the risk of
bleeding.

Infection

Serious infections (bacterial, viral, or fungal), including fatal events
and opportunistic infections, have occurred in the combined safety
database of 612 patients with hematologic malignancies treated with
CALQUENCE monotherapy. Grade 3 or higher infections occurred in 18% of
these patients. The most frequently reported Grade 3 or 4 infection was
pneumonia. Infections due to hepatitis B virus (HBV) reactivation and
progressive multifocal leukoencephalopathy (PML) have occurred.

Monitor patients for signs and symptoms of infection and treat as
medically appropriate. Consider prophylaxis in patients who are at
increased risk for opportunistic infections.

Cytopenias

In the combined safety database of 612 patients with hematologic
malignancies, patients treated with CALQUENCE monotherapy experienced
Grade 3 or 4 cytopenias, including neutropenia (23%), anemia (11%), and
thrombocytopenia (8%), based on laboratory measurements. Monitor
complete blood counts monthly during treatment.

Second Primary Malignancies

Second primary malignancies, including non-skin carcinomas, have
occurred in 11% of patients with hematologic malignancies treated with
CALQUENCE monotherapy in the combined safety database of 612 patients.
The most frequent second primary malignancy was skin cancer, reported in
7% of patients. Advise protection from sun exposure.

Atrial Fibrillation and Flutter

In the combined safety database of 612 patients with hematologic
malignancies treated with CALQUENCE monotherapy, atrial fibrillation and
atrial flutter of any grade occurred in 3% of patients, and Grade 3 in
1% of patients. Monitor for atrial fibrillation and atrial flutter and
manage as appropriate.

ADVERSE REACTIONS

The most common adverse reactions (≥20%) of any grade were anemia,*
thrombocytopenia,* headache (39%), neutropenia,* diarrhea (31%), fatigue
(28%), myalgia (21%), and bruising (21%).

*Treatment-emergent decreases (all grades) of hemoglobin (46%),
platelets (44%), and neutrophils (36%) were based on laboratory
measurements and adverse reactions.

The most common Grade ≥ 3 non-hematological adverse reaction (reported
in at

least 2% of patients) was diarrhea (3.2%).

Dosage reductions or discontinuations due to any adverse reaction were
reported in 1.6% and 6.5% of patients, respectively.

Increases in creatinine 1.5 to 3 times the upper limit of normal
occurred in 4.8% of patients.

DRUG INTERACTIONS

Strong CYP3A Inhibitors: Avoid co-administration with a
strong CYP3A inhibitor. If a strong CYP3A inhibitor will be used
short-term, interrupt CALQUENCE.

Moderate CYP3A Inhibitors: When CALQUENCE is co-administered
with a moderate CYP3A inhibitor, reduce CALQUENCE dose to 100 mg once
daily.

Strong CYP3A Inducers: Avoid co-administration with a strong
CYP3A inducer. If a strong CYP3A inducer cannot be avoided, increase the
CALQUENCE dose to 200 mg twice daily.

Gastric Acid Reducing Agents: If treatment with a gastric
acid reducing agent is required, consider using an H2-receptor
antagonist or an antacid. Take CALQUENCE 2 hours before taking an
H2-receptor antagonist. Separate dosing with an antacid by at least 2
hours.

Avoid co-administration with proton pump inhibitors. Due to the
long-lasting effect of proton pump inhibitors, separation of doses may
not eliminate the interaction with CALQUENCE.

SPECIFIC POPULATIONS

There is insufficient clinical data on CALQUENCE use in pregnant women
to inform a drug-associated risk for major birth defects and
miscarriage. Advise women of the potential risk to a fetus.

It is not known if CALQUENCE is present in human milk. Advise lactating
women not to breastfeed while taking CALQUENCE and for at least 2 weeks
after the final dose.

INDICATIONS

CALQUENCE is a Bruton tyrosine kinase (BTK) inhibitor indicated for the
treatment of adult patients with mantle cell lymphoma (MCL) who have
received at least one prior therapy.

This indication is approved under accelerated approval based on overall
response rate. Continued approval for this indication may be contingent
upon verification and description of clinical benefit in confirmatory
trials.

Please see complete Prescribing
Information
 including Patient Information.

NOTES TO EDITORS

About AstraZeneca in Oncology

AstraZeneca has a deep-rooted heritage in Oncology and offers a
quickly-growing portfolio of new medicines that has the potential to
transform patients' lives and the Company's future. With at least six
new medicines to be launched between 2014 and 2020, and a broad pipeline
of small molecules and biologics in development, we are committed to
advance Oncology as a growth driver for AstraZeneca, focused on lung,
ovarian, breast and blood cancers. In addition to our core capabilities,
we actively pursue innovative partnerships and investments that
accelerate the delivery of our strategy as illustrated by our investment
in Acerta Pharma in hematology.

By harnessing the power of four scientific platforms – Immuno-Oncology,
Tumor Drivers and Resistance, DNA Damage Response and Antibody Drug
Conjugates – and by championing the development of personalized
combinations, AstraZeneca has the vision to redefine cancer treatment
and, one day, eliminate cancer as a cause of death.

About MedImmune

MedImmune is the global biologics research and development arm of
AstraZeneca, a global, innovation-driven biopharmaceutical business that
focuses on the discovery, development and commercialization of small
molecule and biologic prescription medicines. MedImmune is pioneering
innovative research and exploring novel pathways across Oncology,
Respiratory, Cardiovascular, Renal & Metabolic Diseases, and Infection
and Vaccines. The MedImmune headquarters is located in Gaithersburg, MD,
one of AstraZeneca's three global R&D centers, with additional sites in
Cambridge, UK, and South San Francisco, CA. For more information, please
visit www.medimmune.com.

About AstraZeneca

AstraZeneca is a global, science-led biopharmaceutical company that
focuses on the discovery, development and commercialization of
prescription medicines, primarily for the treatment of diseases in three
therapy areas - Oncology, Cardiovascular, Renal & Metabolism and
Respiratory. The Company also is selectively active in the areas of
autoimmunity, neuroscience and infection. AstraZeneca operates in over
100 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 Twitter @AstraZenecaUS.

US-20433 Last Updated 5/18

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