REG - AstraZeneca PLC - Calquence combination approved in EU for 1L MCL

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RNS Number : 4564H  AstraZeneca PLC  06 May 2025

06 May 2025

Calquence plus chemoimmunotherapy approved in the EU

as first and only BTK inhibitor for 1st-line mantle cell lymphoma

Approval based on ECHO Phase III trial results which demonstrated over 16
months of progression-free survival improvement vs. chemoimmunotherapy alone

 

AstraZeneca's Calquence (acalabrutinib) in combination with bendamustine and
rituximab has been approved in the European Union (EU) for the treatment of
adult patients with previously untreated mantle cell lymphoma (MCL) who are
not eligible for autologous stem cell transplant.

 

The approval by the European Commission follows the positive opinion
(https://www.astrazeneca.com/media-centre/press-releases/2025/calquence-recommended-for-eu-approval-in-1l-mcl.html)
of the Committee for Medicinal Products for Human Use and was based on
positive results from ECHO Phase III trial
(https://www.astrazeneca.com/media-centre/press-releases/2024/calquence-plus-chemoimmunotherapy-reduced-the-risk-of-disease-progression-or-death-by-27-percent.html)
, presented at the European Haematology Association (EHA) 2024 Congress and
published in The Journal of Clinical Oncology
(https://ascopubs.org/doi/10.1200/JCO-25-00690) , which demonstrated that
Calquence plus bendamustine and rituximab reduced the risk of disease
progression or death by 27% compared to standard-of-care chemoimmunotherapy
(hazard ratio  HR  0.73; 95% confidence interval  CI  0.57-0.94; p=0.016).
Median progression-free survival (PFS) was 66.4 months for patients treated
with the Calquence combination versus 49.6 with chemoimmunotherapy alone.
 

 

MCL is a rare and typically aggressive form of non-Hodgkin lymphoma, often
diagnosed at an advanced stage.(1,2) An estimated 6,000 patients were
diagnosed with MCL in the UK, France, Germany, Spain and Italy in 2024.(3)

 

Martin Dreyling, MD, Department of Medicine, University Hospital LMU Munich,
and investigator in the trial, said: "This approval provides a new first-line
treatment option for patients in the EU with mantle cell lymphoma, an
aggressive lymphoma with a dismal long-term outcome still today. With a
progression-free survival improvement of more than 16 months for these
patients, the acalabrutinib combination is a much-needed advance in this
challenging disease."

 

Dave Fredrickson, Executive Vice President, Oncology Haematology Business
Unit, AstraZeneca, said: "Treatment with the Calquence combination in
first-line mantle cell lymphoma demonstrated a significant improvement in
progression free survival and a consistent safety profile for patients in the
pivotal ECHO trial. As the first and only BTK inhibitor approved in this
indication in the EU, we are proud to provide a much-needed new option to
patients living with this difficult disease."

 

The safety and tolerability of Calquence was consistent with its known
safety profile, and no new safety signals were identified.

 

Calquence plus bendamustine and rituximab is approved in the US and several
other countries in this setting based on the ECHO results. Regulatory
applications are currently under review in Japan and several other countries
in this indication.

 

This approval follows the recent approval for Calquence monotherapy for the
treatment of adult patients with relapsed or refractory MCL in the EU.

 

Notes

Mantle cell lymphoma (MCL)

While MCL patients initially respond to treatment, patients do tend to
relapse.(4) MCL comprises about 3-6% of non-Hodgkin lymphomas, with an annual
incidence of 0.5 per 100,000 population in Western countries; It is estimated
that there are more than 21,000 patients diagnosed with MCL in the US, UK,
France, Germany, Spain, Italy, Japan and China.(3,4,5)

 

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 SoC chemoimmunotherapy (bendamustine and rituximab) in
adult patients at or over 65 years of age (n=635) with previously untreated
MCL.(6) Patients were randomised 1:1 to receive either Calquence or placebo
administered orally twice per day, continuously, until disease progression or
unacceptable toxicity. Additionally, all patients received six 28-day cycles
of bendamustine on days 1 and 2 and rituximab on day 1 of each cycle, followed
by rituximab maintenance for two years if patients achieved a response after
induction therapy.(6)

 

The primary endpoint is PFS assessed by an Independent Review Committee; other
efficacy endpoints include overall survival (OS), overall response rate,
duration of response and time to response.(6) The trial was conducted in 27
countries across North and South America, Europe, Asia and Oceania.(6)

 

The ECHO trial enrolled patients from May 2017 to March 2023, continuing
through the COVID-19 pandemic. Prespecified PFS and OS analyses censoring for
COVID-19 deaths were conducted to assess the impact of COVID-19 on the study
outcome in alignment with the FDA.

 

Calquence
Calquence is a second-generation, selective inhibitor of Bruton's tyrosine
kinase (BTK). Calquence binds covalently to BTK, thereby inhibiting its
activity.(7) In B-cells, BTK signalling results in activation of pathways
necessary for B-cell proliferation, trafficking, chemotaxis and adhesion.

 

Calquence is approved for the treatment of chronic lymphocytic leukaemia (CLL)
and small lymphocytic lymphoma (SLL) in the US, Japan and China, and approved
for CLL in the EU and many other countries. Calquence is also approved for
the treatment of adult patients with previously untreated MCL in the US and
other countries. It is also approved for the treatment of adult patients with
MCL who have received at least one prior therapy in China and several other
countries. Calquence is not currently approved for the treatment of MCL in
Japan.

 

As part of an extensive clinical development programme, Calquence is
currently being evaluated as a single treatment and in combination with
standard-of-care chemoimmunotherapy for patients with multiple B-cell blood
cancers, including CLL, MCL and diffuse large B-cell lymphoma.

 

AstraZeneca in haematology

AstraZeneca is pushing the boundaries of science to redefine care in
haematology. Our goal is to help transform the lives of patients living with
malignant, rare and other related haematologic diseases through innovative
medicines and approaches that are shaped by insights from patients, caregivers
and physicians.

 

In addition to our marketed products, we are spearheading the development of
novel therapies designed to target underlying drivers of disease across
multiple scientific platforms. Our acquisitions of Alexion, with expertise in
rare, non-malignant blood disorders, and Gracell Biotechnologies Inc.,
pioneers of autologous cell therapies, expand our haematology pipeline and
enable us to reach more patients with high unmet needs through the end-to-end
discovery, development and delivery of novel therapies.

 

AstraZeneca in oncology

AstraZeneca is leading a revolution in oncology with the ambition to provide
cures for cancer in every form, following the science to understand cancer and
all its complexities to discover, develop and deliver life-changing medicines
to patients.

 

The Company's focus is on some of the most challenging cancers. It is through
persistent innovation that AstraZeneca has built one of the most diverse
portfolios and pipelines in the industry, with the potential to catalyse
changes in the practice of medicine and transform the patient experience.

 

AstraZeneca has the vision to redefine cancer care and, one day, eliminate
cancer as a cause of death.

 

AstraZeneca
AstraZeneca (LSE/STO/Nasdaq: AZN) is a global, science-led biopharmaceutical
company that focuses on the discovery, development, and commercialisation of
prescription medicines in Oncology, Rare Diseases, and BioPharmaceuticals,
including Cardiovascular, Renal & Metabolism, and Respiratory &
Immunology. Based in Cambridge, UK, AstraZeneca's innovative medicines are
sold in more than 125 countries and used by millions of patients worldwide.
Please visit astrazeneca.com (http://www.astrazeneca.com/)  and follow the
Company on Social Media @AstraZeneca
(https://www.linkedin.com/company/astrazeneca) .

 

Contacts

For details on how to contact the Investor Relations Team, please click here
(https://www.astrazeneca.com/investor-relations.html#Contacts) . For Media
contacts, click here (https://www.astrazeneca.com/media-centre/contacts.html)
.

 

References

1.   Lymphoma Research Foundation. Mantle Cell Lymphoma. Available at:
https://lymphoma.org/aboutlymphoma/nhl/mcl/
(https://lymphoma.org/aboutlymphoma/nhl/mcl/) . Accessed April 2025.

2.   National Organization for Rare Disorders. Mantle Cell Lymphoma.
Available at: https://rarediseases.org/rare-diseases/mantle-cell-lymphoma/
(https://rarediseases.org/rare-diseases/mantle-cell-lymphoma/) . Accessed
April 2025.

3.   AstraZeneca 2024. Q3 2024 Financial Results. Available at:
https://www.astrazeneca.com/investor-relations.html
(https://www.astrazeneca.com/investor-relations.html) . Accessed April 2025.

4.   Cheah C, Seymour J, Wang ML. Mantle cell lymphoma. J Clin Oncol.
2016;34(11):1256-1269. doi: 10.1200/JCO.2015.63.5904.

5.   Lynch DT, Koya S, Acharya U, et al. Mantle Cell Lymphoma. Available at:
https://www.ncbi.nlm.nih.gov/books/NBK536985/
(https://www.ncbi.nlm.nih.gov/books/NBK536985/) . Accessed April 2025.

6.   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.
(https://clinicaltrials.gov/study/NCT02972840.%20Accessed%20November%202024)
Accessed April 2025.

7.   Wu J, et al. Acalabrutinib (ACP-196): a selective second-generation BTK
inhibitor. J Hematol Oncol. 2016;9(21).

 

Matthew Bowden

Company Secretary

AstraZeneca PLC

 

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