FORM 6-K
SECURITIES
AND EXCHANGE COMMISSION
Washington,
D.C. 20549
Report
of Foreign Issuer
Pursuant
to Rule 13a-16 or 15d-16 of
the
Securities Exchange Act of 1934
For the
month of June 2025
Commission
File Number: 001-11960
AstraZeneca PLC
1
Francis Crick Avenue
Cambridge
Biomedical Campus
Cambridge
CB2 0AA
United
Kingdom
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AstraZeneca PLC
INDEX
TO EXHIBITS
1.
Fixed-duration Calquence approved in EU for 1L CLL
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 of the Committee
for Medicinal Products for Human Use and was based on positive
results from the pivotal AMPLIFY Phase III
trial, presented at the
American Society of Hematology 2024 Annual Meeting and published
in The
New England Journal of Medicine.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 and
follow the Company on Social Media @AstraZeneca.
Contacts
For details on how to contact the Investor Relations Team, please
click here.
For Media contacts, click here.
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.
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.
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.
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.
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
SIGNATURES
Pursuant
to the requirements of the Securities Exchange Act of 1934, the
Registrant has duly caused this report to be signed on its behalf
by the undersigned, thereunto duly authorized.
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AstraZeneca
PLC
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Date:
06 June 2025
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By: /s/
Adrian Kemp
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Name:
Adrian Kemp
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Title:
Company Secretary
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