New long-term data on Calquence presented at ASH 2018

26 months median duration of response achieved in relapsed mor refractory mantle cell lymphoma at updated two-year analysis1

97% overall response rate in treatment-naïve chronic lymphocytic leukaemia trial population at three and a half years2

AstraZeneca and Acerta Pharma, its haematology research and development centre of excellence, have presented new, long-term follow-up results for Calquence (acalabrutinib) in patients with relapsed or refractory mantle cell lymphoma (MCL), and updated results of an ongoing clinical trial assessing Calquence monotherapy in treatment-naïve patients with chronic lymphocytic leukaemia (CLL), at the 60th American Society of Hematology (ASH) Annual Meeting & Exposition in San Diego, CA, USA.

Sean Bohen, Executive Vice President, Global Medicines Development and Chief Medical Officer, said: “The data from these two clinical trials validate previous findings and add to the growing body of evidence that support the promise of Calquence in multiple blood cancers. We are very encouraged by these results, which reinforce our commitment to advancing innovative treatments for blood cancer patients.”

Calquence follow-up data in MCL confirms efficacy and tolerability

Long-term follow-up data presented from the Phase II ACE-LY-004 trial in relapsed or refractory MCL showed sustained and clinically meaningful responses to Calquence with a median follow-up of more than two years (26 months), confirming its efficacy and safety profile in this patient population.1 Initial data from this trial served as the basis for the accelerated approval of Calquence by the US Food and Drug Administration in October 2017 and the first approval outside the US in November 2018 in the United Arab Emirates.3,4

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 trial, said: “It’s encouraging to see the sustained duration of response in the updated analysis and the safety profile of acalabrutinib maintained consistently over time in MCL patients. As we gain more and more experience with this therapy, its importance as a treatment option for relapsed or refractory MCL is being more fully realised across the clinical and patient community.” 

Summary of key investigator-assesseda efficacy results from the open-label, single-arm clinical trial of Calquence in 124 adult patients with relapsed or refractory MCL1:

Efficacy measure Result (N=124; 95% CIb)
Overall response rate (Complete response + partial response) 81% (73, 87)
Best response
                      Complete response 43% (34, 52)
                      Partial response 38% (29, 47)
                      Stable disease 9% (5, 15)
                      Progressive disease 8% (4, 14)
                      Not evaluablec 2% (1, 7)
Median duration of response 26 months (17.5, not reached)
Median progression-free survival 20 months (16.5, 27.7)

a Response was assessed based on the Lugano classification.

b Confidence interval (CI).

c Includes patients without any adequate post-baseline disease assessment.

The median follow-up was 26 months, with 40% of patients remaining on treatment with Calquence at the time of analysis. An exploratory analysis of the trial found that an undetectable minimal residual disease status was achieved in a sub-set of patients.

In this trial, the most frequent adverse events (AEs; ≥ 20%, all grades) were headache (38%), diarrhoea (36%), fatigue (28%), cough (22%) and myalgia (21%). These events were primarily Grade 1/2. Grade 3/4 AEs (≥ 5%) were anaemia (11%), neutropoenia (11%) and pneumonia (6%). There were 13 patients (10%) with 16 cardiac events including four Grade 3/4 events, each in one patient (acute coronary syndrome, acute myocardial infarction, cardiorespiratory arrest, coronary artery disease). There was no new onset of atrial fibrillation. Bleeding events occurred in 33% of patients, most frequently contusion (13%) and all bleeding events but three (2%, Grade 3) were Grade 1/2 events. Ten patients discontinued treatment due to AEs. In total there were six deaths due to AEs (none of which were considered to be related to Calquence).1  

New data from ongoing CLL clinical trial demonstrate strong efficacy

Updated results of the Phase I/II ACE-CL-001 trial were presented today in an oral session. In a cohort of treatment-naïve patients with CLL, long-term safety and efficacy of assessment showed high response rates with no new safety signals identified. The median time on trial was 42 months, with 89% of patients remaining on treatment with Calquence at the time of analysis.2

John C. Byrd, MD, Distinguished University Professor, The Ohio State University, and Principal Investigator for the ACE-CL-001 CLL clinical trial, said: “A key challenge in the treatment of CLL is ensuring patients have therapies that they can tolerate and benefit from over the long term. The results seen in this patient cohort at 3.5 years of follow-up are encouraging for both durability of response and tolerability of therapy. We look forward to continued data from ongoing studies evaluating acalabrutinib in CLL.”

Summary of key investigator-assesseda efficacy results from the Phase I/II open-label, single-arm ACE-CL-001 Calquence trial in 99 patients with CLL, evaluating the treatment-naïve cohort2:

Efficacy measure Result (N=99)
Overall response rate (Complete response + partial response) 97%
Complete response 5%
Partial response 92%
Median duration of responseb NR (range, 42.4 to NR)c
                      36 month duration of response rate (95% CI)b,d,e 98% (90, 99)
Median progression-free survival NR (range, 44.2 to NR)c
                      36 month progression-free survival rate (95% CI)d,e 97% (91, 99)

a Response was assessed using International Workshop on Chronic Lymphocytic Leukemia (IWCLL) 2008 criteria with modification for lymphocytosis.

b Only responders with ≥ partial response were included in this analysis.

c Not reached (NR).

d Confidence interval (CI).

e Based on the Kaplan-Meier estimates.

In this trial, the most common AEs (≥ 20%, all grades) were diarrhoea (49%), headache (44%), upper respiratory tract infection (40%), contusion (39%), arthralgia (33%), weight increased (31%), nausea (30%) and cough (23%). Grade 3/4 AEs (≥ 5%) were neutropenia (8%), hypertension (7%), diarrhoea (5%) and headache (5%). Atrial fibrillation and hypertension (all grades) occurred in 6% and 17% of patients, respectively, with Grade 3 events occurring in 2% and 7% of patients. Bleeding events (all grades) occurred in 64% of patients with contusion being most common (39%). All but three (3% Grade 3) bleeding events were Grade 1/2 events and no patients discontinued due to bleeding. Overall, 11% of patients discontinued treatment, 5% of which were due to AEs, including secondary malignancies (angiosarcoma, glioblastoma multiforme, small cell lung cancer), sepsis (Grade 4) and urinary tract infection (Grade 3). One Grade 5 event (multiorgan failure) in the setting of pneumonia was reported, which was considered unrelated to Calquence.2

-ENDS-

NOTES TO EDITORS

About Calquence

Calquence (acalabrutinib) is an inhibitor of Bruton tyrosine kinase (BTK). Calquence binds covalently to BTK, thereby inhibiting its activity.3 In B cells, BTK signalling results in activation of pathways necessary for B cell proliferation, trafficking, chemotaxis, and adhesion.3

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. Calquence is not currently licensed for the treatment of chronic lymphocytic leukaemia (CLL).

Calquence was granted Orphan Drug designation by the European Commission in 2016 and the US FDA in 2015 for the treatment of patients with CLL, MCL and Waldenstrom's macroglobulinemia; 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 uncommon type of B-cell non-Hodgkin lymphoma.5,6,7 MCL comprises 3% to 6% of non-Hodgkin lymphomas, with an annual incidence of 0.5 per 100,000 population in Western countries; in the US, it was estimated that approximately 3,300 new cases of MCL were diagnosed in 2016.5,8 The median age at diagnosis is 68 years,5 with MCL occurring more than twice as often in men than women.7 While MCL patients initially respond to treatment, there is a high relapse rate.5

About chronic lymphocytic leukaemia (CLL)

CLL is the most common type of leukaemia in adults and accounts for approximately one in four cases of leukaemia.9,10 The average age at the time of diagnosis is approximately 70 years of age.10 In CLL, too many blood stem cells in the bone marrow become abnormal lymphocytes and these abnormal cells have difficulty fighting infections.9 As the number of abnormal cells grows there is less room for healthy white blood cells, red blood cells and platelets.9 This could result in anaemia, infection and bleeding.9 B cell receptor signalling through BTK is one of the essential growth pathways for CLL.

About AstraZeneca in haematology

Leveraging its strength in oncology, AstraZeneca has established haematology as one of four key oncology disease areas of focus. The Company’s haematology franchise includes two US FDA-approved medicines and a robust global development programme for a broad portfolio of potential blood cancer treatments. Acerta Pharma serves as AstraZeneca’s haematology research and development centre of excellence. AstraZeneca partners with like-minded science-led companies to advance the discovery and development of therapies to address unmet need.

In October 2018, AstraZeneca and Innate Pharma announced a global strategic collaboration that included Innate Pharma licensing the US commercial rights of Lumoxiti (moxetumomab pasudotox-tdfk), and with support from AstraZeneca, will continue EU development and commercialisation, pending regulatory submission and approval.

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 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.

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 commercialisation of small molecule and biologic prescription medicines. MedImmune is pioneering innovative research and exploring novel pathways across Oncology, Respiratory, Cardiovascular, Renal and 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 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 commercialisation 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.com and follow us on Twitter @AstraZeneca.

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References 

1.      Wang M, Rule S, Zinzani PL, et al. Long-Term Follow-Up of Acalabrutinib Monotherapy in Patients With Relapsed/Refractory Mantle Cell Lymphoma. Poster presentation at: American Society of Hematology 2018 Annual Meeting; December 2018; San Diego, CA. Abstract #2876. 

2.      Byrd J, Woyach J, et al. Acalabrutinib in Treatment-Naïve (TN) Chronic Lymphocytic Leukemia (CLL): Updated Results from the Phase 1/2 ACE-CL-001 Study. Oral presentation at: American Society of Hematology 2018 Annual Meeting; December 2018; San Diego, CA. Abstract #692.

3.      CALQUENCE® (acalabrutinib) Prescribing Information. AstraZeneca Pharmaceuticals LP, Wilmington, DE.  

4.      Wang M, Rule S, Zinzani PL, et al. Acalabrutinib in relapsed or refractory mantle cell lymphoma (ACE-LY-004): a single-arm, multicentre, phase 2 trial. The Lancet. 2017;391(10121):659-667.

5.      Cheah CY, Seymour JF, Wang M. Mantle Cell Lymphoma. Journal of Clinical Oncology. 2016;34(11):1256-1269.

6.      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(13):1338-1346.

7.      Zhou Y, Wang H, Fang W, et al. Incidence trends of mantle cell lymphoma in the United States between 1992 and 2004. Cancer. 2008;113(4):791-798.

8.      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.

9.      National Cancer Institute. Chronic Lymphocytic Leukemia Treatment (PDQ®)–Patient Version. Available online. Accessed November 2018.

American Cancer Society. What are the key statistics for chronic lymphocytic leukemia? Available online. Accessed November 2018.

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