REG - AstraZeneca PLC - Fixed-duration Calquence approved in EU for 1L CLL

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06/06/2025 07:00

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RNS Number : 7063L  AstraZeneca PLC  06 June 2025

06 June 2025

Fixed-duration Calquence-based regimens approved in EU for patients with
chronic lymphocytic leukaemia in the 1st-line setting

AMPLIFY Phase III trial results demonstrated statistically significant and
clinically meaningful improvement in progression-free survival for Calquence
combinations

 

A fixed-duration regimen of AstraZeneca's Calquence (acalabrutinib) in
combination with venetoclax, with or without obinutuzumab, has been approved
in the European Union (EU) for the treatment of adult patients with previously
untreated chronic lymphocytic leukaemia (CLL).

 

The approval by the European Commission follows the positive opinion
(https://www.astrazeneca.com/media-centre/press-releases/2025/fixed-duration-calquence-recommended-in-eu-for-cll.html)
of the Committee for Medicinal Products for Human Use and was based on
positive results from the pivotal AMPLIFY Phase III trial
(https://www.astrazeneca.com/media-centre/press-releases/2024/fixed-duration-calquence-plus-venetoclax-demonstrated-superior-pfs-vs-standard-care-previously-untreated-cll-with-77-of-patients-progression-free-3-years-amplify-phase-iii-trial.html)
, presented at the American Society of Hematology 2024 Annual Meeting and
published in The New England Journal of Medicine (https://www.nejm.org/) .(1)

 

Results from the AMPLIFY trial showed 77% of patients treated with Calquence
plus venetoclax and 83% of patients treated with Calquence plus venetoclax and
obinutuzumab were progression free at three years, versus 67% of patients
treated with standard-of-care chemoimmunotherapy (investigator's choice of
fludarabine-cyclophosphamide-rituximab or bendamustine-rituximab).(1) Median
progression-free survival (PFS) was not reached for either experimental arm
versus 47.6 months for chemoimmunotherapy.(1) Calquence plus venetoclax
reduced the risk of disease progression or death by 35% compared to
chemoimmunotherapy (hazard ratio  HR  0.65; 95% confidence interval  CI 
0.49-0.87; p=0.0038). Calquence plus venetoclax with obinutuzumab demonstrated
a 58% reduction in the risk of disease progression or death compared to
chemoimmunotherapy (HR 0.42; 95% CI 0.30-0.59; p<0.0001).(2)

 

CLL is the most common type of leukaemia in adults. An estimated 27,000 people
were diagnosed with CLL in the UK, France, Germany, Spain and Italy in
2024.(3)

 

Barbara Eichhorst, MD, University Hospital Cologne, Cologne, Germany and
investigator for the AMPLIFY trial, said: "For patients diagnosed with chronic
lymphocytic leukaemia, this approval provides a new option in the first-line
setting that may help to minimize long-term side effects and reduce drug
resistance as they may occur with continuous treatment. A fixed-duration
regimen is appealing to patients and helps with adherence during the treatment
period."

 

Dave Fredrickson, Executive Vice President, Oncology Haematology Business
Unit, AstraZeneca, said: "Today's approval brings a new fixed-duration
treatment option to patients with previously untreated chronic lymphocytic
leukaemia across Europe. Calquence plus venetoclax is the first and only
all-oral combination treatment option with a second-generation BTK inhibitor
approved in the EU and provides patients and their physicians more flexibility
in managing this incurable blood cancer."

 

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

 

Regulatory applications for these regimens are currently under review in
several countries based on the AMPLIFY results.

Notes
Chronic lymphocytic leukaemia (CLL)

CLL is the most prevalent type of leukaemia in adults, with an estimated
40,000 people being treated for CLL in the first line in the US, UK, France,
Germany, Spain, Italy, Japan and China in 2024.(3) Although some people with
CLL may not experience any symptoms at diagnosis, others may experience
symptoms, such as weakness, fatigue, weight loss, chills, fever, night sweats,
swollen lymph nodes and abdominal pain.(4) In CLL, there is an accumulation of
abnormal lymphocytes within the blood, bone marrow and lymph nodes. As the
number of abnormal cells increases, there is less room within the marrow for
the production of normal white blood cells, red blood cells and platelets.(5)
This could result in infection, anaemia and bleeding. B-cell receptor
signalling through BTK is one of the essential growth pathways for CLL.

AMPLIFY

AMPLIFY is a randomised, global, multi-centre, open-label Phase III trial
evaluating the efficacy and safety of Calquence in combination with
venetoclax, with or without obinutuzumab, compared to investigator's choice of
chemoimmunotherapy (fludarabine-cyclophosphamide-rituximab or
bendamustine-rituximab) in adult patients with previously untreated CLL
without del(17p) or TP53 mutation.(6) Patients were randomised 1:1:1 to
receive either Calquence plus venetoclax, or Calquence plus venetoclax with
obinutuzumab for a fixed duration, or standard-of-care chemoimmunotherapy.(6)
Both the Calquence containing arms were administered for a fixed duration of
14 cycles (each 28 days), and the standard-of-care chemoimmunotherapy was for
6 cycles.(6)

 

The primary endpoint is PFS in the Calquence and venetoclax arm as assessed by
an Independent Review Committee, and PFS in the Calquence plus venetoclax with
obinutuzumab arm is a key secondary endpoint.(6) Other key secondary endpoints
include overall survival (OS) and undetectable measurable residual disease.(6)
The trial includes 27 countries across North and South America, Europe, Asia
and Oceania.(6)

 

The AMPLIFY trial enrolled patients from 2019 to 2021, continuing through the
COVID-19 pandemic.(6)

 

Calquence
Calquence (acalabrutinib) is a second-generation, selective inhibitor of
Bruton's tyrosine kinase (BTK). Calquence binds covalently to BTK, thereby
inhibiting its activity.(8) 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 in
combination with venetoclax, with or without obinutuzumab, as a fixed-duration
treatment for CLL in the EU. Calquence is also approved for the treatment of
adult patients with previously untreated mantle cell lymphoma (MCL) in the US,
Europe 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

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.

 

References

1.   Brown J, et al. Fixed-duration acalabrutinib combinations in untreated
chronic lymphocytic leukemia. NEJM. 2025;392:748-762.

2.   Brown, J et al. Fixed-duration acalabrutinib plus venetoclax with or
without obinutuzumab versus chemoimmunotherapy for first-line treatment of
chronic lymphocytic leukemia: interim analysis of the multicenter, open-label,
randomized, Phase 3 AMPLIFY Trial. Presented at ASH 2024. Abstract 1009. 2024.

3.   AstraZeneca 2024. Full Year and Q4 2024 Financial Results Epidemiology
Spreadsheet. Available at: https://www.astrazeneca.com/investor-relations.html
(https://www.astrazeneca.com/investor-relations.html) . Accessed May 2025.

4.   American Cancer Society. Signs and Symptoms of Chronic Lymphocytic
Leukemia. Available at:
https://www.cancer.org/cancer/types/chronic-lymphocytic-leukemia/detection-diagnosis-staging/signs-symptoms.html
(https://www.cancer.org/cancer/types/chronic-lymphocytic-leukemia/detection-diagnosis-staging/signs-symptoms.html)
. Accessed May 2025.

5.   National Cancer Institute. Chronic lymphocytic leukemia treatment
(PDQ(®))-Patient version. Available at:
https://www.cancer.gov/types/leukemia/patient/cll-treatment-pdq
(https://www.cancer.gov/types/leukemia/patient/cll-treatment-pdq) . Accessed
May 2025.

6.   ClinicalTrials.gov. Study of Acalabrutinib (ACP-196) in Combination
With Venetoclax (ABT-199), With and Without Obinutuzumab (GA101) Versus
Chemoimmunotherapy for Previously Untreated CLL (AMPLIFY). Available at:
https://clinicaltrials.gov/study/NCT03836261
(https://clinicaltrials.gov/study/NCT03836261) . Accessed May 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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