On December 3, 2018 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) (Free ASH Whitepaper) Annual Meeting & Exposition in San Diego, CA, USA (Press release, AstraZeneca, DEC 3, 2018, View Source [SID1234531822]).
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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
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