17 January 2025
Calquence
plus
chemoimmunotherapy approved in the US
for
patients with previously
untreated mantle cell lymphoma
Based on ECHO Phase III trial
results which showed more than 16 months of progression-free
survival improvement vs. chemoimmunotherapy alone
First and only BTK inhibitor
approved for the 1st-line treatment of MCL in the
US
AstraZeneca's Calquence (acalabrutinib) in
combination with bendamustine and rituximab has been approved in
the US for the treatment of adult patients with previously
untreated mantle cell lymphoma (MCL) who are ineligible for
autologous hematopoietic stem cell transplantation.
The approval was granted by the Food and Drug
Administration (FDA) after securing
Priority Review. It was based on results from the
ECHO Phase III trial which were presented at the European
Hematology Association 2024 Congress.
MCL is a rare and typically aggressive form of
non-Hodgkin lymphoma (NHL), often diagnosed at an advanced
stage.[1],[2] 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]
Michael Wang, MD, Puddin Clarke Endowed
Professor, Director of Mantle Cell Lymphoma Program of Excellence
and principal investigator in the trial, said: "Managing this
aggressive cancer requires maximising efficacy while maintaining
tolerability, especially for elderly patients. Results from the
pivotal ECHO trial highlight the promise of the acalabrutinib
combination in defining a new standard of care, with today's
approval underscoring the transformative potential of this regimen
as a first-line treatment for older patients with mantle cell
lymphoma."
Dave Fredrickson, Executive Vice-President,
Oncology Haematology Business Unit, AstraZeneca, said: "With
today's approval, Calquence provides a critical new
treatment option to mantle cell lymphoma patients in the US, with
Calquence proven to
deliver nearly one and a half years of additional time without
disease progression. This approval brings a new and effective
treatment option to those living with this disease and further
reinforces our belief in Calquence as a backbone therapy across
multiple blood cancers."
Meghan Gutierrez, Chief Executive Officer,
Lymphoma Research Foundation, said: "New treatment options have
long been needed in the first-line treatment of mantle cell
lymphoma in the US. Patients with this rare and often aggressive
cancer can experience severe symptoms by the time they are
diagnosed - having an effective therapy that can significantly
improve outcomes for patients early in the treatment process is a
much-needed advancement."
Results from the ECHO trial showed 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 PFS
was 66.4 months for patients treated with the Calquence combination versus 49.6
months with chemoimmunotherapy alone.
This approval additionally converts
Calquence's accelerated
approval to a full approval for adult patients with MCL treated
with at least one prior therapy, as granted by the FDA in October
2017.
The ECHO trial enrolled patients throughout the
COVID-19 pandemic. After censoring for COVID-19 deaths, PFS was
further improved in both arms, with the Calquence combination reducing
the risk of disease progression or death by 36% (HR 0.64; 95% CI
0.48-0.84). Although OS data were not mature at the time of the
analysis, when censored for COVID-19, a favourable trend was seen
for OS (HR 0.75; 95% CI 0.53-1.04), despite 69% of patients in the
chemoimmunotherapy arm receiving treatment with a BTK inhibitor on
relapse or disease progression.
The safety and tolerability
of Calquence was
consistent with its known safety profile, and no new safety signals
were identified.
The US regulatory submission was reviewed under
Project Orbis, which provides a framework for concurrent submission
and review of oncology medicines among participating international
partners. As part of Project Orbis, Calquence plus chemoimmunotherapy is
also under review by regulatory authorities in Australia, Canada,
and Switzerland for the same indication. Regulatory applications
are also under review in the EU, Japan, and other countries based
on the ECHO results.
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; in the US, it is estimated that approximately
4,000 new patients are diagnosed with MCL each
year.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 OS, overall response rate (ORR), duration of response (DoR)
and time to response (TTR).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. 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.6,[7]
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 has been used to treat more than 85,000 patients
worldwide[9] and is
approved for the treatment of chronic lymphocytic leukaemia (CLL)
and small lymphocytic lymphoma (SLL) in the US and Japan, approved
for CLL in the EU and many other countries worldwide and approved
in China for relapsed or refractory CLL and SLL. Calquence is also approved for the
treatment of adult patients with previously untreated MCL in the
US, and in China and several other countries for the treatment of
adult patients with mantle cell lymphoma (MCL) who have received at
least one prior therapy. Calquence is not currently approved
for the treatment of MCL in Japan or the EU.
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,
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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.
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The Company's focus is on some of the most
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AstraZeneca (LSE/STO/Nasdaq: AZN) is a global, science-led
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