AZN AstraZeneca PLC

First data presentation of CALQUENCE®, (acalabrutinib), recently approved in the US for patients with previously-treated mantle cell lymphoma

New data on five compounds in development across six types of blood cancer

AstraZeneca, along with Acerta Pharma, its hematology research and development center of excellence, and MedImmune, its global biologics research and development arm, will highlight significant progress in blood cancer research at the 59th 2017 American Society of Hematology (ASH) Annual Meeting & Exhibition in Atlanta. Presentations will include new data from AstraZeneca’s emerging hematology portfolio in several cancer types including mantle cell lymphoma (MCL), chronic lymphocytic leukemia (CLL), hairy cell leukemia (HCL), acute myeloid leukemia (AML), multiple myeloma and diffuse large B-cell lymphoma (DLBCL).

Sean Bohen, Executive Vice President, Global Medicines Development and Chief Medical Officer at AstraZeneca, said: “Following the recent accelerated approval of AstraZeneca’s first medicine for a blood cancer, CALQUENCE, we will share a broad range of new data at ASH highlighting our scientific progress in hematology as we seek to develop potential medicines that advance patient care.”

CALQUENCE (acalabrutinib) is a kinase inhibitor indicated for the treatment of adult patients with mantle cell lymphoma (MCL) who have received at least one prior therapy. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.

Efficacy and safety of CALQUENCE in treatment of previously-treated MCL

Following the US Food and Drug Administration (FDA) accelerated approval of CALQUENCE, data from the pivotal Phase II ACE-LY-004 clinical trial on which the accelerated approval was based, will be presented for the first time (Abstract #155). New details of the trial will be shared, including median time to response, pre-specified patient subgroup efficacy analyses, as well as safety analyses, further characterizing the clinical profile of CALQUENCE in this patient population.

Acalabrutinib as monotherapy and in combination in multiple CLL patient populations

Results will be presented from the Phase Ib/II ACE-CL-003 trial evaluating acalabrutinib and obinutuzumab in treatment-naïve and previously-treated CLL patients (Abstract #432), which highlight data on the safety profile and activity of the combination. Long-term follow-up safety and efficacy data from the Phase I/II ACE-CL-001 clinical trial which is testing acalabrutinib as a monotherapy in a large cohort of patients with relapsed or refractory CLL (Abstract #498) will expand on findings previously reported; these data will also highlight the duration of response in this patient population.

Early-stage hematology portfolio

• AstraZeneca will present additional data from its haematology portfolio, including findings from a Phase I trial of moxetumomab pasudotox, an anti-CD22 recombinant immunotoxin and potential new medicine in development for the treatment of people with previously-treated HCL (Abstract: #2765)
• Early data on AZD2811, a novel nanoparticle inhibitor of aurora kinase B being tested in AML (Abstract #1368)
• Preclinical data from trials on MEDI2228, a BCMA-targeting pyrrolobenzodiazepine-linked antibody drug conjugate being tested in multiple myeloma (Abstract #3153)
• Data from a trial of vistusertib (AZD2014), a dual mTORC1/2 inhibitor being tested in DLBCL (Abstract #4113)

IMPORTANT SAFETY INFORMATION ABOUT CALQUENCE

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.

Please see complete Prescribing Information including Patient Information.

NOTES TO EDITORS

A full list of company-sponsored abstracts to be presented at ASH are as follows:

  Abstract Number     Title     Presentation Details Abstract #155     Efficacy and safety of acalabrutinib monotherapy in patients with relapsed/refractory mantle cell lymphoma in the Phase II ACE-LY-004 Study     Oral session, Saturday, December 9, 1 p.m. EST

 

Location: Georgia World Congress Center, Building A, Level 4, A411-A412

Abstract #1741     Pharmacodynamic evaluation of acalabrutinib in relapsed/refractory and treatment-naive patients with chronic lymphocytic leukemia in the Phase I/II ACE-CL-001 study     Poster sessions, Saturday, December 9, 5:30-7:30 p.m. EST

 

Location: Georgia World Congress Center, Building A, Level 1, Hall A2

Abstract: #1268     Exposure-response of the Bruton tyrosine kinase inhibitor, acalabrutinib in the treatment of hematologic malignancies Abstract #1243    

Concurrent treatment with Pim kinase inhibitor downregulates alternative non-homologous end-joining repair and decreases genomic instability in FLT3-ITD cells treated with topoisomerase 2 inhibitors

Abstract #1368     Preclinical and early Phase I clinical data of AZD2811 nanoparticle in AML, an aurora B kinase inhibitor     Abstract #432     Acalabrutinib with obinutuzumab in relapsed/refractory and treatment-naive patients with chronic lymphocytic leukemia: The phase Ib/II ACE-CL-003 study     Oral session, Sunday, December 10, 1:15 p.m. EST

 

Location: Georgia World Congress Center, Building B, Level 5, Murphy BR 3-4

Abstract #498     Acalabrutinib monotherapy in patients with relapsed/refractory chronic lymphocytic leukemia: Updated results from the Phase I/II ACE-CL-001 study     Oral session, Sunday, December 10, 5:45 p.m. EST

 

Location: Georgia World Congress Center, Building B, Level 5, Murphy BR 3-4

Abstract: #2765     Negative minimal residual disease associated with extended response to moxetumomab pasudotox in patients with relapsed/refractory hairy cell leukemia: long-term follow-up of bone marrow immunohistochemistry analyses from a Phase 1 study Poster Session, Sunday, December 10, 6-8 p.m. EST

 

Location: Georgia World Congress Center, Building A, Level 1, Hall A2

Abstract: #3153     Preclinical evaluation of MEDI2228, a BCMA-targeting pyrrolobenzodiazepine-linked antibody drug conjugate for the treatment of multiple myeloma Abstract #3442     Adverse events, resource use, and economic burden in patients with mantle cell lymphoma in the United States     Abstract #4326     Pooled analysis of safety data from clinical trials evaluating acalabrutinib monotherapy in hematologic malignancies Poster sessions, Monday, December 11, 6-8 p.m. EST

 

Location: Georgia World Congress Center, Building A, Level 1, Hall A2

Abstract #4060     Understanding ibrutinib treatment discontinuation patterns for chronic lymphocytic leukemia Abstract #4684     MCL treatment patterns and outcomes: A community oncology practice experience Abstract #4113     Combined inhibition of mTOR and BTK signaling is required for optimal long-term growth inhibition in DLBCL models      

About AstraZeneca in Oncology

AstraZeneca has a deep-rooted heritage in Oncology and offers a quickly growing portfolio of new medicines that have 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 New Oncology as one of AstraZeneca’s five Growth Platforms 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 Acerta Pharma

Acerta Pharma, a member of the AstraZeneca Group, is creating novel therapies intended for the treatment of cancer and autoimmune diseases. AstraZeneca acquired a majority stake interest in Acerta Pharma, which serves as AstraZeneca’s hematology research and development center of excellence. For more information, please visit www.acerta-pharma.com.

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 & Metabolic Diseases; and Infection and Vaccines. The MedImmune headquarters is located in Gaithersburg, Md., one of AstraZeneca’s three global R&D centres, with additional sites in Cambridge, UK, and Mountain View, 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 main therapy areas – Oncology, Cardiovascular & Metabolic Diseases 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-16351 Last Updated 12/17

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AstraZenecaMichele Meixell, +1 302-885-2677Stephanie Wiswall, +1 302-885-2677