81% overall response rate and 40% complete response rate by investigator assessment with consistent results observed across pre-specified subgroups of patients
CAMBRIDGE, ENGLAND--(Business Wire
) December 11, 2017 -- AstraZeneca and Acerta Pharma, its haematology research and development centre of excellence, today presented results from the open-label, single-arm Phase II ACE-LY-004 clinical trial, which served as the basis for the recent US Food and Drug Administration (FDA) accelerated approval of Calquence (acalabrutinib). The findings were presented for the first time during an oral session at the 59th American Society of Hematology (ASH) Annual Meeting & Exhibition in Atlanta, USA and demonstrate the safety profile and efficacy of acalabrutinib in the management of previously-treated mantle cell lymphoma (MCL).
Sean Bohen, Executive Vice President, Global Medicines Development and Chief Medical Officer at AstraZeneca, said: “The results presented for the first time to the medical community highlight the potential of Calquence as a treatment for people with relapsed or refractory mantle cell lymphoma, a life-threatening form of blood cancer. These data reinforce the important progress of our clinical development programme as well as our commitment to advancing the treatment of patients with blood cancers.”
Michael L. Wang, MD, Professor, Department of Lymphoma/Myeloma, The University of Texas MD Anderson Cancer Center, and Principal Investigator of the ACE-LY-004 MCL clinical trial, said: “Most people living with mantle cell lymphoma will unfortunately relapse, and new treatment options are greatly needed. As shown by the consistent overall response rates observed in this trial across several pre-specified subgroups, acalabrutinib is a welcome new treatment option for certain patients with this aggressive blood cancer.”
Summary of key investigator-assessed efficacy results from ACE-LY-004 (15.2 months median follow-up):
(To view the table, please visit https://goo.gl/Wsc8sr
Per the 2014 Lugano classification response criteria for non-Hodgkin lymphoma; high concordance was observed between investigator-assessed and independent review committee-assessed overall response and complete response rates, respectively.
The overall response rate was consistent across multiple subgroups including age, tumour burden and number or type of prior treatments. The secondary endpoint of median duration of response had not yet been reached at 15.2 months median follow-up. The median time-to-response, an exploratory endpoint, was 1.9 months. After 12 months of treatment, 72% (95% CI: 62,80) of patients were still responding to acalabrutinib treatment. The secondary endpoints of progression-free survival and overall survival had not yet been reached; at 12 months, the progression-free survival and overall survival rates were 67% (95% CI: 58,75) and 87% (95% CI: 79,92), respectively.
In this trial, the most common non-haematological adverse reactions (reported in ≥20% of patients at a median follow-up time of 15.2 months) were headache (38%), diarrhoea (30%), fatigue (26%) and myalgia (21%), per investigator assessment. Grade 3 or 4 adverse reactions (≥5%) included anaemia (12%), neutropenia (11%), and pneumonia (6%).
Calquence was granted accelerated approval by the US FDA in October 2017 for the treatment of adult patients with MCL who have received at least one prior therapy. This indication is approved based on overall response rate, and continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.
About Calquence (acalabrutinib)
Acalabrutinib (previously known as ACP-196) is a selective inhibitor of BTK. Acalabrutinib binds covalently to BTK, thereby inhibiting its activity, and has demonstrated this with minimal interactions with other immune cells in pre-clinical studies.[2,3,4] In B cells, BTK signalling results in activation of pathways necessary for B-cell proliferation, trafficking, chemotaxis and adhesion.
Calquence was granted accelerated approval by the US Food and Drug Administration (FDA) in October 2017 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. Acalabrutinib is not approved for use outside of its labelled indication in the US and is not approved in any other country at this time.
Acalabrutinib is also in development for the treatment of multiple B-cell malignancies and other blood cancers including 1st-line MCL, chronic lymphocytic leukaemia (CLL), Waldenström macroglobulinaemia (WM), follicular lymphoma, diffuse large B-cell lymphoma, and multiple myeloma. It is also being developed as a monotherapy and in combination trials for solid tumours. More than 35 clinical trials across 40 countries with more than 2,500 patients are underway or have been completed.
Acalabrutinib was granted Orphan Drug Designation by the European Commission in March 2016 and the US FDA in 2015 for the treatment of patients with CLL, MCL and WM, and Breakthrough Therapy Designation in August 2017 by the US FDA for the treatment of patients with MCL who have received at least one prior therapy.
About Mantle Cell Lymphoma (MCL)
MCL is an aggressive B-cell non-Hodgkin lymphoma (NHL) with poor prognosis.[6,7,8,9] MCL accounts for approximately 3% to 6% of new NHL cases in Western countries each year; in the US, approximately 3,300 new cases of MCL are diagnosed each year.[6,10] The median age at diagnosis is 68 years, with a 3:1 male predominance.7 While MCL patients initially respond to treatment, there is a high relapse rate.
About the ACE-LY-004 Trial
ACE-LY-004 is a Phase II open-label, single-arm clinical trial in 124 adult patients with relapsed or refractory MCL. The trial showed that 81% (95% CI: 73,87) of patients treated with acalabrutinib achieved an overall response; 40% (95% CI: 31,49) achieved a complete response and 41% (95% CI: 32,50) achieved a partial response, per 2014 Lugano classification as assessed by investigator.
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 aimed 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 haematology.
By harnessing the power of four scientific platforms - Immuno-Oncology, Tumour Drivers and Resistance, DNA Damage Response and Antibody Drug Conjugates - and by championing the development of personalised 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 haematology research and development centre of excellence. For more information, please visit www.acerta-pharma.com
AstraZeneca is a global, science-led biopharmaceutical company that focuses on the discovery, development and commercialisation of prescription medicines, primarily for the treatment of diseases in three 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.com
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This press release is issued from AstraZeneca Corporate Headquarters in Cambridge, UK and is intended to provide information about our global business. Please be aware that information relating to the approval status and labels of approved products may vary from country to country, and a country-specific press release on this topic may have been issued in the countries where AstraZeneca conducts business.
 Data on File. REF-23706. AstraZeneca Pharmaceuticals LP, Wilmington, DE.
 Calquence (acalabrutinib) Prescribing Information. AstraZeneca Pharmaceuticals LP, Wilmington, DE
 Covey T, Barf T, Gulrajani M, Krantz F, van Lith B, Bibikova E, et al. Abstract 2596: ACP-196: a novel covalent Bruton’s tyrosine kinase (Btk) inhibitor with improved selectivity and in vivo target coverage in chronic lymphocytic leukemia (CLL) patients. Cancer Res. 2015;75(15 Supplement):2596.
 Harrington BK, Gulrajani M, Covey T, Kaptein A, Van Lith B, Izumi R, et al. ACP-196 is a second generation inhibitor of Bruton tyrosine kinase (BTK) with enhanced target specificity. Blood. 2015;126(23):2908.
 Data on File. REF US-15441. AstraZeneca Pharmaceuticals LP, Wilmington, DE.
 Leukemia & Lymphoma Society. Mantle Cell Lymphoma Facts. https://www.lls.org/sites/default/files/file_assets/mantlecelllymphoma.pdf.
Accessed June 2017
 Cheah CY, Seymour JF, Wang M. Mantle Cell Lymphoma. Journal of Clinical Oncology 34, no. 11 (April 2016) 1256-1269.
 Hoster E, Klapper W et al. Confirmation of the Mantle-Cell Lymphoma International Prognostic Index in Randomized Trials of the European Mantle-Cell Lymphoma Network. Journal of Clinical Oncology 2014;32:1338-1346.
 Dreyling M, Ferrero S. The role of targeted treatment in mantle cell lymphoma: is transplant dead or alive? Haematologica 2016 Volume 101(2):104-114
 Teras LR, DeSantis CE, Cerhan JR, et al. 2016 US lymphoid malignancy statistics by World Health Organization subtypes. CA Cancer J Clin. 2016;66:443-459.
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