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 May 2024
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.
Calquence
combination improved PFS in 1L MCL
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
AstraZeneca is pushing the boundaries of science to redefine care
in haematology. We have expanded our commitment to patients with
haematologic conditions, 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.
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 operates in over
100 countries and its innovative medicines are 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.
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
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.
Date:
02 May 2024
|
By: /s/
Adrian Kemp
|
|
Name:
Adrian Kemp
|
|
Title:
Company Secretary
|