02 May 2024
Calquence combination
regimen
demonstrated statistically significant and clinically meaningful
improvement in progression-free survival in 1st-line mantle cell
lymphoma in ECHO Phase III trial
First BTK inhibitor to show
favourable trend in overall survival
vs. standard-of-care
chemoimmunotherapy in this setting
Positive high-level results from an
interim analysis of the ECHO Phase III trial showed AstraZeneca's
Calquence (acalabrutinib)
in combination with standard-of-care chemoimmunotherapy,
bendamustine and rituximab, demonstrated a statistically
significant and clinically meaningful improvement in
progression-free survival (PFS) versus standard of care in
previously untreated adult patients with mantle cell lymphoma
(MCL).
A trend was observed in favour of
Calquence plus
chemoimmunotherapy for the secondary endpoint of overall survival
(OS). The OS data were not mature at the time of this analysis and
the trial will continue to assess OS.
MCL is a rare and typically
aggressive form of non-Hodgkin lymphoma (NHL), often diagnosed as a
late-stage disease, resulting when B-lymphocytes mutate into
malignant cells within a region of the lymph node known as the
mantle zone.1,2 It is estimated
that there are more than 27,500 patients diagnosed with MCL
worldwide.3,4
Michael Wang, MD, Puddin Clarke
Endowed Professor, Director of Mantle Cell Lymphoma Program of
Excellence, Co-Director of Clinical Trials at MD Anderson Cancer
Center in Houston, US and principal investigator in the trial,
said: "These positive progression-free survival results from the
ECHO Phase III trial could provide a new standard of care for
patients with mantle cell lymphoma. Incorporating Calquence into the first-line mantle
cell lymphoma setting would give many more patients the opportunity
to benefit from the robust efficacy and strong safety profile we've
seen with this medicine."
Susan Galbraith, Executive Vice
President, Oncology R&D, AstraZeneca, said: "These impactful
results in mantle cell lymphoma show that bringing Calquence to the first-line setting
significantly delays disease progression and, for the first time,
shows potential to extend survival. The improvement in
progression-free survival together with the differentiated safety
profile of Calquence are
both important as we strive to transform outcomes earlier in the
course of disease treatment."
The safety and tolerability of
Calquence was consistent
with its known safety profile, and no new safety signals were
identified.
The data will be presented at a
forthcoming medical meeting and shared with global regulatory
authorities.
As part of an extensive clinical
development programme, AstraZeneca is currently evaluating
Calquence alone and in
combination for the treatment of multiple B-cell blood cancers,
including chronic lymphocytic leukaemia (CLL), MCL, and diffuse
large B-cell lymphoma.
Calquence has been used to
treat more than 80,000 patients worldwide and is approved for the
treatment of CLL and small lymphocytic lymphoma (SLL) in the US,
approved for CLL in the EU and many other countries worldwide and
approved in Japan and China for relapsed or refractory CLL and SLL.
Calquence is also approved
in the US, China and several other countries for the treatment of
adult patients with MCL who have received at least one prior
therapy. Calquence is not
currently approved for the treatment of MCL in Japan or the
EU.
Notes
Mantle cell lymphoma
MCL is an uncommon subtype of B-cell
non-Hodgkin lymphoma.5 MCL comprises about 3-6% of
non-Hodgkin lymphomas, with an annual incidence of 0.5 per 100,000
population in Western countries; in the US, it is estimated that
approximately 4,000 new cases of MCL are diagnosed each
year.5,6 While MCL patients initially respond to
treatment, patients do tend to relapse.5
ECHO
ECHO is a randomised, double-blind,
placebo-controlled, multi-centre Phase III trial evaluating the
efficacy and safety of Calquence plus bendamustine and
rituximab compared to standard of care chemoimmunotherapy
(bendamustine and rituximab) in adult patients at or over 65 years
of age (n=598) with previously untreated MCL.7 In the
experimental arms, patients were randomised 1:1 to receive either
Calquence or placebo
administered orally twice per day, on 28 day treatment cycles, plus
bendamustine on days 1 and 2 and rituximab on day 1. After six
cycles of Calquence or
placebo in combination with bendamustine and rituximab, patients
receive Calquence or
placebo plus maintenance rituximab for two years and then either
Calquence or placebo only until disease
progression.7
The primary endpoint is PFS and key
secondary endpoints include OS, overall response rate (ORR),
duration of response (DoR) and time to response (TTR).7
The trial includes 27 countries across North and South America,
Europe, Asia and Oceania.7
The ECHO trial was conducted from
2017 to 2023 continuing through the COVID-19 pandemic. Patients
with blood cancer remain at a disproportionately high risk of
severe outcomes from COVID-19, including hospitalisation and death
compared to the general population.8
Calquence
Calquence (acalabrutinib) is a
next-generation, selective inhibitor of Bruton's tyrosine kinase
(BTK). Calquence binds
covalently to BTK, thereby inhibiting its activity.9 In
B cells, BTK signalling results in activation of pathways necessary
for B-cell proliferation, trafficking, chemotaxis and
adhesion.
AstraZeneca in haematology
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boundaries of science to redefine care in haematology. We have
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not only in oncology but also in rare diseases with the acquisition
of Alexion, allowing us to reach more patients with high unmet
needs. By applying our deep understanding of blood cancers,
leveraging our strength in solid tumour oncology and delivering on
Alexion's pioneering legacy in complement science to provide
innovative medicines for rare diseases, we are pursuing the
end-to-end development of novel therapies designed to target
underlying drivers of disease. Following AstraZeneca's recent
acquisition of Gracell Biotechnologies Inc., we have broadened our
pipeline of innovative cell therapies with a differentiated
manufacturing process to potentially further address haematologic
malignancies.
By targeting haematologic conditions
with high unmet medical needs, we aim to deliver innovative
medicines and approaches to improve patient outcomes. Our goal is
to help transform the lives of patients living with malignant, rare
and other related haematologic diseases, shaped by insights from
patients, caregivers and physicians to have the most meaningful
impact.
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References
1. Lymphoma Research
Foundation. Mantle Cell Lymphoma. Available at:
https://lymphoma.org/aboutlymphoma/nhl/mcl/. Accessed April
2024.
2. National Organization
for Rare Disorders. Mantle Cell Lymphoma. Available at:
https://rarediseases.org/rare-diseases/mantle-cell-lymphoma/.
Accessed April 2024.
3. GLOBOCAN. Non-Hodgkin
Lymphoma. Available at:
https://gco.iarc.who.int/media/globocan/factsheets/cancers/34-non-hodgkin-lymphoma-fact-sheet.pdf.
Accessed April 2024.
4. Lynch DT, Koya S,
Acharya U, et al. Mantle Cell Lymphoma. Available at:
https://www.ncbi.nlm.nih.gov/books/NBK536985/.
Accessed April 2024.
5. Cheah C, Seymour J,
Wang ML. Mantle cell lymphoma. J Clin Oncol. 2016;34(11):1256-1269.
doi: 10.1200/JCO.2015.63.5904.
6. MD Anderson Cancer
Center. What to know about mantle cell lymphoma. Available
at:
https://www.mdanderson.org/cancerwise/what-to-know-about-mantle-cell-lymphoma-symptoms-diagnosis-and-treatment.h00-159385101.html.
Accessed April 2024.
7. ClinicalTrials.gov. A
Study of BR Alone Versus in Combination With Acalabrutinib in
Subjects With Previously Untreated MCL. Available at:
https://clinicaltrials.gov/study/NCT02972840. Accessed April
2024.
8. Dube S, et al.
Continued Increased Risk of COVID-19 Hospitalisation and Death in
Immunocompromised Individuals Despite Receipt of ≥4 Vaccine Doses:
Updated 2023 Results from INFORM, a Retrospective Health Database
Study in England. Poster P0409 at ECCMID 2024
9. Wu J, Zhang M, Liu D.
Acalabrutinib (ACP-196): a selective second-generation BTK
inhibitor. J Hematol
Oncol. 2016;9(21).
Adrian Kemp
Company Secretary
AstraZeneca PLC