REG - AstraZeneca PLC - Calquence fixed-duration combo improved 1L CLL PFS

AstraZenecaAnnouncement

29/07/2024 07:00

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RNS Number : 1029Y  AstraZeneca PLC  29 July 2024

 

29 July 2024

 

Fixed-duration Calquence plus venetoclax, with or without obinutuzumab,
significantly improved progression-free survival in 1st-line chronic
lymphocytic leukaemia in AMPLIFY Phase III trial

 

Favourable trend in overall survival was also observed

 

Positive high-level results from an interim analysis of the AMPLIFY Phase III
trial showed a fixed duration of AstraZeneca's Calquence (acalabrutinib) in
combination with venetoclax, with or without obinutuzumab, demonstrated a
statistically significant and clinically meaningful improvement in
progression-free survival (PFS) compared to standard-of-care
chemoimmunotherapy in previously untreated adult patients with chronic
lymphocytic leukaemia (CLL).

 

For the secondary endpoint of overall survival (OS), a trend was observed in
favour of Calquence in combination with venetoclax, with or without
obinutuzumab, versus standard-of-care chemoimmunotherapy. The OS data were not
mature at the time of this analysis and the trial will continue to assess OS
as a key secondary endpoint.

 

CLL is caused by the abnormal production of white blood cells and is the most
prevalent type of leukaemia in adults worldwide, with numbers anticipated to
grow.(1-3) In the first-line setting, approximately 40,000 patients are
treated with the current standard of care.(4) Although CLL is considered an
incurable cancer, patients often live with the disease for many years, and may
 remain on continuous treatment.(5)

 

Jennifer R. 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 trial, said: "The AMPLIFY results demonstrate
the potential of acalabrutinib and venetoclax with or without obinutuzumab to
be effective and well-tolerated fixed-duration treatment options for patients
with chronic lymphocytic leukaemia. This is an important advance in this
setting as fixed-duration regimens allow those living with this chronic
disease to take breaks from their treatment, thereby decreasing the
possibility of long-term adverse events and drug resistance and improving
quality of life."

 

Susan Galbraith, Executive Vice President, Oncology R&D, AstraZeneca,
said: "The progression-free survival and overall survival results from the
AMPLIFY Phase III trial demonstrate the potential of including a BTK inhibitor
in a fixed-duration regimen and reinforce our leadership in advancing science
for patients with chronic lymphocytic leukaemia. If approved, Calquence would
become the only second-generation BTK inhibitor available as both a
treat-to-progression and fixed-duration treatment, providing more options for
patients and their healthcare providers."

 

The safety and tolerability were consistent with the known safety profile of
each medicine. No new safety signals were identified, with low rates of
cardiac toxicity observed.

 

The data will be presented at a forthcoming medical meeting and shared with
global regulatory authorities.

 

Notes

 

CLL

In CLL, there is an accumulation of abnormal lymphocytes within the bone
marrow and in blood and lymph nodes.(1) 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.(6) 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. This could result in anaemia, infection and
bleeding.(1) B-cell receptor signalling through BTK is one of the essential
survival 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 and without obinutuzumab compared to investigator's choice of
chemoimmunotherapy in adult patients with previously untreated CLL without
del(17p) or TP53 mutation.(7) Patients were randomised 1:1:1 to receive either
Calquence in combination with venetoclax, Calquence in combination with
venetoclax plus obinutuzumab for a fixed duration or standard-of-care
chemoimmunotherapy.(7)

 

The primary endpoint is PFS in the Calquence and venetoclax arm as assessed by
an Independent Review Committee (IRC) and PFS in this arm assessed by
investigators (INV) is a key secondary endpoint. IRC and INV assessed PFS in
the Calquence, venetoclax and obinutuzumab arm as a key secondary endpoint.
Other key secondary endpoints include OS, event-free survival, overall
response rate, duration of response and time to next treatment.(7) The trial
includes 27 countries across North and South America, Europe, Asia and
Oceania.(7)

 

The AMPLIFY trial enrolled patients from 2019 to 2021, continuing through the
COVID-19 pandemic.(7) 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 second-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.

 

Calquence has been used to treat more than 80,000 patients worldwide(10) and
is approved for the treatment of 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 in the US, 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, 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 six
scientific platforms. Our recent acquisitions of Alexion, with expertise in
rare, non-malignant blood disorders, and Gracell Biotechnologies Inc., focused
on cell therapies for haematologic malignancies, expand our haematology
pipeline and enable us to reach more patients with high unmet needs through
the end-to-end 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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(https://www.astrazeneca.com/investor-relations.html#Contacts) . For Media
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.

 

References

1.   National Cancer Institute. Chronic Lymphocytic Leukemia Treatment
(PDQ®)-Patient Version: General Information About Chronic Lymphocytic
Leukemia. Available online. Accessed July 2024.

2.   American Cancer Society. What is Chronic Lymphocytic Leukemia?
Available online. Accessed July 2024.

3.   Jain N, et al. Prevalence and Economic Burden of Chronic Lymphocytic
Leukemia (CLL) in the Era of Oral Targeted Therapies. Blood. 2015;126(23):871.

4.   Cerner CancerMPact and DRG databases. Reflects epidemiology estimates
across G8 countries (Cerner CancerMPact for G7: US, EU, Japan; DRG database
for China). Accessed July 2024.

5.   American Cancer Society. After Chronic Lymphocytic Leukemia Treatment.
Available at:
https://www.cancer.org/cancer/types/chronic-lymphocytic-leukemia/after-treatment/follow-up.
Accessed July 2024.

6.   American Cancer Society. Signs and Symptoms of Chronic Lymphocytic
Leukemia. Available online. Accessed July 2024.

7.   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 July 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).

10.  Data on File, REF-236261. AstraZeneca Pharmaceuticals LP.

 

Adrian Kemp

Company Secretary

AstraZeneca PLC

 

 

 

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