REG - AstraZeneca PLC - Fixed-duration Calquence combo approved in US

AstraZenecaAnnouncement

20/02/2026 07:00

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RNS Number : 7829T  AstraZeneca PLC  20 February 2026

20 February 2026

Calquence plus venetoclax approved in the US as first all-oral, fixed-duration
combination for patients with chronic lymphocytic leukaemia in the 1st-line
setting

Calquence plus venetoclax demonstrated statistically significant and
clinically meaningful improvement in progression-free survival vs.
chemoimmunotherapy, with 77% of patients progression free at three years in
AMPLIFY Phase III trial

AstraZeneca's Calquence (acalabrutinib) in combination with venetoclax has
been approved in the US as the first all-oral, fixed-duration regimen for the
treatment of adult patients with chronic lymphocytic leukaemia (CLL) and small
lymphocytic lymphoma (SLL).

 

The approval by the US Food and Drug Administration (FDA) was based on
positive results from the AMPLIFY
(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)
Phase III trial, which were presented at the American Society of Hematology
2024 Annual Meeting and published in The New England Journal of Medicine
(https://www.nejm.org) .(1,2)

 

CLL is the most common type of leukaemia in adults.(3) An estimated 18,500
people were treated for CLL in the 1st-line setting in the US in 2024.(4)

 

Jennifer Brown, MD, PhD, Director of the CLL Center of the Division of
Hematologic Malignancies, Dana-Farber Cancer Institute, and the Worthington
and Margaret Collette Professor of Medicine at Harvard Medical School, and
principal investigator of the AMPLIFY trial, said: "The continuous regimens
frequently used to treat chronic lymphocytic leukaemia often come with side
effects that may become burdensome to patients over time. The US approval of
the Calquence combination offers patients an all-oral, 14-month,
fixed-duration treatment option that is highly effective and well-tolerated,
and gives physicians greater flexibility to tailor treatment plans for
individual patient needs and goals."

 

Dave Fredrickson, Executive Vice President, Oncology Haematology Business
Unit, AstraZeneca, said: "Today's approval delivers the first all-oral,
fixed-duration BTK inhibitor-based regimen in the US for the treatment of
chronic lymphocytic leukaemia. This Calquence combination has the potential to
meaningfully change 1st-line chronic lymphocytic leukaemia treatment decisions
and underscores our commitment to improving on the current standard of care
for people living with blood cancers."

 

Gwen Nichols, MD, Chief Medical Officer of Blood Cancer United, formerly The
Leukemia & Lymphoma Society, said: "Managing an incurable blood
cancer that progresses slowly can often feel indefinite and overwhelming. We
welcome new treatment options that may ease the burden, restore a sense of
control and offer renewed hope for those navigating life with chronic
lymphocytic leukaemia."

 

Results from the AMPLIFY Phase III trial showed 77% of patients treated with
Calquence plus venetoclax were progression free at three years, versus 67% of
patients treated with standard-of-care chemotherapy (investigator's choice of
fludarabine-cyclophosphamide-rituximab or bendamustine-rituximab).(2) Median
progression-free survival (PFS) was not reached versus 47.6 months for
chemoimmunotherapy.(2) Further, Calquence plus venetoclax reduced the risk of
disease progression or death by 35% compared to chemoimmunotherapy (based on
hazard ratio 0.65; 95% confidence interval 0.49-0.87; p=0.0038).(2)

 

Calquence plus venetoclax is approved
(https://www.astrazeneca.com/media-centre/press-releases/2025/fixed-duration-calquence-approved-in-eu-for-1l-cll.html#:~:text=The%20approval%20by%20the%20European,New%20England%20Journal%20of%20Medicine.)
in the European Union, Canada, UK and several other countries, and regulatory
applications for the regimen based on the AMPLIFY results are currently under
review in additional countries.

 

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

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.(4) 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.(5) 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.(3)
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
administered for 6 cycles.(6)

 

The primary endpoint is PFS in the Calquence and venetoclax arm as assessed by
an Independent Review Committee, and PFS is a key secondary endpoint in the
Calquence plus venetoclax with obinutuzumab arm.(7) 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.(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 Europe and many other countries. Calquence is also approved as a
fixed-duration treatment for the treatment of adult patients with previously
untreated CLL in combination with venetoclax in the US, and in combination
with venetoclax, with or without obinutuzumab, in Europe, Canada, the U.K. and
several other countries. Calquence is also approved for the treatment of
adult patients with previously untreated mantle cell lymphoma (MCL) in the US,
Europe, Japan 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.

 

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/NYSE: 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
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.

 

References

1.   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.

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

3.   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
February 2026.

4.   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 February
2026.

5.   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 February 2026.

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 February 2026.

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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