AstraZeneca Continues to Redefine Cancer Treatment at The 2019 ASCO Annual Meeting

WILMINGTON, Del.--(BUSINESS WIRE)-- AstraZeneca will present new research across an industry-leading Oncology portfolio, including data for its transformational cancer medicines LYNPARZA^® (olaparib) and IMFINZI^® (durvalumab) at the 2019 American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago, May 31 to June 4, 2019.

In all, the Company will present 93 abstracts spanning multiple tumor types, including 12 oral presentations with one plenary session and four late-breakers. Highlights include:

• Late-breaking results from the LYNPARZA POLO trial, the first positive Phase III trial of any PARP inhibitor in germline BRCA-mutated (gBRCAm) metastatic pancreatic cancer, a devastating diagnosis with critical unmet medical need. This is the first Phase III trial to validate a targeted treatment in a biomarker-selected population of pancreatic cancer.
• Results of the Phase III SOLO-3 trial highlighting the efficacy and safety for LYNPARZA monotherapy vs. standard-of-care chemotherapy in treating patients with gBRCAm advanced ovarian cancer who had two or more prior lines of treatment. This data underscores LYNPARZA’s clinical benefit irrespective of line of therapy for women with BRCAm advanced ovarian cancer and the importance of knowing BRCA status at diagnosis.
• Three-year overall survival (OS) data from the Phase III PACIFIC trial providing new longer-term survival evidence for IMFINZI in unresectable, Stage III non-small cell lung cancer (NSCLC) in patients whose disease had not progressed following chemoradiation therapy. IMFINZI is the only immunotherapy to have demonstrated significant OS benefits in this curative-intent setting, and these updated data reaffirm the PACIFIC regimen as a standard of care for these patients.

Dave Fredrickson, Executive Vice President, Oncology, said: “AstraZeneca continues to break traditional treatment boundaries through new targeted approaches and the prioritization of earlier intervention. This year at ASCO, our data for LYNPARZA in BRCA-mutated metastatic pancreatic cancer and for IMFINZI in unresectable Stage III non-small cell lung cancer illustrate our ambition to change medical practice for better patient outcomes.”

Breaking treatment boundaries

AstraZeneca is committed to redefining disease treatment for patient populations with unmet needs. This will be evidenced at the ASCO meeting for patients with BRCA-mutated PARP-mediated tumors, those with HER2-low expressing tumors or those with AKT-mutated tumors.

The plenary presentation of results from the Phase III POLO trial will detail the progression-free survival (PFS) and important clinical activity of LYNPARZA in patients with metastatic pancreatic cancer, a population that has seen very little treatment progress over the past 40 years (Abstract #LBA4).

New data on LYNPARZA will also be shared in advanced ovarian cancer, including the results of the Phase III SOLO-3 trial highlighting the efficacy and safety for LYNPARZA monotherapy vs. standard-of-care chemotherapy in treating patients with gBRCAm advanced ovarian cancer who had two or more prior lines of treatment (Abstract #5506).

Furthermore, the Phase II TOPARP-B trial, sponsored by the Institute of Cancer Research (UK), will highlight the anti-tumor activity of LYNPARZA in patients with heavily pretreated metastatic castration resistant prostate cancer with DDR gene defects (Abstract #5005). The Phase II GeparOLA trial, conducted by the German Breast Group and German AGO-B Breast Study Group, will help define the safety and efficacy of LYNPARZA, compared to platinum-based chemotherapy, in the neoadjuvant setting in HER2-negative early breast cancer and in patients with homologous recombination deficiency (Abstract #506).

The design of the Phase III DESTINY-Breast04 trial evaluating trastuzumab deruxtecan (DS-8201) in metastatic breast cancer with HER2-low expressing tumors will be presented at this year’s ASCO meeting (Abstract #TPS1102). This antibody-drug conjugate (ADC) co-developed with Daiichi Sankyo has the potential to redefine breast cancer treatment. Two publications in Lancet Oncology recently highlighted the Phase I dose-expansion results for trastuzumab deruxtecan in HER2-positive metastatic breast and gastric cancers.

In addition, data will be presented from the Phase II FAKTION trial, sponsored by Velindre NHS Trust, on the combination of the AKT inhibitor capivasertib (AZD5363) plus FASLODEX^® (fulvestrant) in patients with relapsed metastatic estrogen receptor (ER)-positive breast cancer (Abstract #1005). AKT mutations occur across several different cancers and may be a target for therapy tailored to tumor genes rather than cancer types.

Treating patients earlier in their disease

AstraZeneca made a significant breakthrough in the treatment of NSCLC beginning in 2017 with the Phase III PACIFIC trial demonstrating unprecedented PFS and subsequently OS benefits for patients with unresectable Stage III NSCLC treated with IMFINZI following concurrent chemoradiotherapy vs. standard of care. At this year’s ASCO meeting, AstraZeneca will provide new longer-term survival evidence of IMFINZI with a three-year OS update (Abstract #8526).

Sub-analysis presentations of Phase III data from SOLO-1, the only trial of a PARP inhibitor to demonstrate improvement in PFS for women with BRCAm advanced ovarian cancer as a 1st-line maintenance treatment, will reinforce the potential of using LYNPARZA earlier in the treatment pathway (Abstract #5539).

Raising the bar for better outcomes

New data from the Phase III FLAURA trial will explore clinical outcomes associated with the detection of epidermal growth factor receptor (EGFR) mutations in plasma at three or six weeks after starting treatment with TAGRISSO^® (osimertinib) (Abstract #9020). With the presentation of the Phase II SAVANNAH trial design, AstraZeneca will explain how it will explore the combination of TAGRISSO and savolitinib to potentially overcome MET-driven EGFR tyrosine kinase inhibitor (TKI) resistance following TAGRISSO treatment in EGFR-mutated NSCLC (Abstract #TPS9119).

Despite recent therapeutic progress, platinum-resistant ovarian cancer remains a therapeutic challenge. Results of a multicenter, double-blind Phase II trial conducted by the Princess Margaret, California, Chicago and Mayo Phase II Consortia will show for the first time increased OS data with the Wee-1 inhibitor adavosertib when associated with the antimetabolite therapy Gemcitabine (Abstract #5518).

A focus on hematology

Our diverse hematology pipeline aims to deliver therapies in a range of blood cancers with critical unmet medical need

AstraZeneca has established hematology as one of its key areas of focus. At the ASCO meeting and the upcoming 24th Congress of the European Hematology Association (EHA), June 13-16, 2019, the Company will present long-term trial follow-up data showing the promising response rate, duration of response and safety profile of the Bruton’s tyrosine kinase (BTK) inhibitor CALQUENCE^® (acalabrutinib) in chronic lymphocytic leukemia (CLL), including:

• Three-year results from the Phase Ib/II ACE-CL-003 trial evaluating CALQUENCE and obinutuzumab in treatment-naïve and previously-treated CLL (Abstract #7500).
• 19-month results from the Phase II ACE-CL-208 trial of CALQUENCE in patients with relapsed or refractory CLL intolerant to ibrutinib (Abstract #7530).

These data are part of a robust development program that includes two pivotal clinical trials for CALQUENCE in CLL with data anticipated in 2019: the Phase III ASCEND (ACE-CL-309) trial in relapsed or refractory CLL, which recently met its primary endpoint, and the ongoing Phase III ELEVATE-TN (ACE-CL-007) trial evaluating CALQUENCE® with and without obinutuzumab in 1st-line CLL.

Key AstraZeneca presentations at ASCO 2019

In addition to the scientific presentations and press releases planned at the ASCO meeting, AstraZeneca and its partner MSD (MSD: known as Merck & Co., Inc. inside the US and Canada) will host a press briefing on Sunday, June 2, on LYNPARZA. For more information, please contact AstraZeneca Media Relations.

SELECT SAFETY INFORMATION for LYNPARZA® (olaparib) tablets

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

The most common adverse reactions (>/10%) in clinical trials were nausea, fatigue (including asthenia), anemia, vomiting, abdominal pain, dizziness, diarrhea, neutropenia, leukopenia, nasopharyngitis/upper respiratory tract infection, arthralgia/myalgia, dysgeusia, headache, dyspepsia, decreased appetite, constipation and stomatitis.

INDICATIONS

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

First-Line Maintenance BRCAm Advanced Ovarian Cancer

For the maintenance treatment of adult patients with deleterious or suspected deleterious germline or somatic

BRCA-mutated (gBRCAm or sBRCAm) advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in complete or partial response to first-line platinum-based chemotherapy. Select patients with gBRCAm advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer for therapy based on an FDA-approved companion diagnostic for LYNPARZA.

Maintenance Recurrent Ovarian Cancer

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.

Advanced gBRCAm Ovarian Cancer

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.

gBRCAm, HER2-Negative Metastatic Breast Cancer

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).

SELECT SAFETY INFORMATION for IMFINZI^® (durvalumab) injection for intravenous use

There are no contraindications for IMFINZI.

IMFINZI can cause immune-mediated adverse reactions, including immune-mediated pneumonitis, hepatitis, colitis or diarrhea, endocrinopathies (including thyroid disorders, adrenal insufficiency, type 1 diabetes, and hypophysitis), nephritis, dermatologic reactions, and other immune-mediated adverse reactions; infection; and infusion-related. Please refer to the full Prescribing Information for important dosage modification and management information specific to adverse reactions.

Serious, potentially fatal risks were seen with IMFINZI. Serious adverse reactions occurred in 29% of patients with unresectable Stage III NSCLC receiving IMFINZI (n=475). The most frequent serious adverse reactions (≥2% of patients) were pneumonitis or radiation pneumonitis (7%) and pneumonia (6%). 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%).

Advise women not to become pregnant or breastfeed during treatment with IMFINZI and for at least 3 months after the last dose.

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

INDICATION

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 Patient Information (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.

SELECT SAFETY INFORMATION for CALQUENCE® (acalabrutinib) capsules

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.

INDICATION AND USAGE

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.

– ENDS –

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 key 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 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. 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-29530 Last Updated 5/19

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