AstraZeneca’s Calquence Combination Therapy Approved for Untreated CLL in Europe Following Positive AMPLIFY Phase III Results

(IN BRIEF) AstraZeneca’s Calquence, in combination with venetoclax, with or without obinutuzumab, has been approved by the European Commission for the treatment of adult patients with previously untreated chronic lymphocytic leukaemia (CLL). The approval follows the positive results from the AMPLIFY Phase III trial, which showed that the Calquence combinations significantly improved progression-free survival compared to standard chemoimmunotherapy. This fixed-duration regimen offers a promising new treatment option for CLL patients and aligns with AstraZeneca’s commitment to advancing therapies for hematologic diseases.

(PRESS RELEASE) CAMBRIDGE, 7-Jun-2025 — /EuropaWire/ — AstraZeneca is pleased to announce that the European Commission has approved a fixed-duration regimen of Calquence (acalabrutinib) in combination with venetoclax, with or without obinutuzumab, for the treatment of adult patients with previously untreated chronic lymphocytic leukaemia (CLL). This approval follows a positive opinion from the Committee for Medicinal Products for Human Use and is based on the encouraging 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.

The AMPLIFY trial demonstrated that 77% of patients treated with Calquence plus venetoclax and 83% of those treated with Calquence plus venetoclax and obinutuzumab were progression-free at three years, compared to 67% of patients treated with standard-of-care chemoimmunotherapy (investigator’s choice of fludarabine-cyclophosphamide-rituximab or bendamustine-rituximab). Furthermore, the median progression-free survival (PFS) was not reached for the experimental arms, while PFS for chemoimmunotherapy was 47.6 months. Calquence plus venetoclax demonstrated a 35% reduction in the risk of disease progression or death compared to chemoimmunotherapy (hazard ratio [HR] 0.65; 95% confidence interval [CI] 0.49-0.87; p=0.0038), while Calquence plus venetoclax with obinutuzumab showed a 58% reduction in the risk of progression or death (HR 0.42; 95% CI 0.30-0.59; p<0.0001).

CLL, the Most Common Type of Leukemia in Adults

Chronic lymphocytic leukaemia (CLL) is the most common form of leukemia in adults, with an estimated 27,000 new diagnoses in the UK, France, Germany, Spain, and Italy in 2024. Patients with CLL often experience symptoms such as fatigue, weight loss, and swollen lymph nodes, as abnormal lymphocytes accumulate in the blood and bone marrow, affecting the production of healthy blood cells.

Dr. Barbara Eichhorst, Investigator for the AMPLIFY Trial, Remarks:

“For patients diagnosed with CLL, this approval offers a new first-line treatment option that could minimize long-term side effects and reduce the risk of drug resistance. A fixed-duration regimen is particularly appealing to patients and supports better adherence throughout treatment,” says Dr. Barbara Eichhorst, MD, University Hospital Cologne.

Dave Fredrickson, EVP, Oncology Haematology Business Unit, AstraZeneca, Comments:

“Today’s approval provides patients across Europe with a new fixed-duration treatment option for previously untreated CLL. Calquence plus venetoclax is the first and only all-oral combination with a second-generation BTK inhibitor approved in the EU, offering greater flexibility for patients and physicians in managing this difficult-to-treat blood cancer,” said Dave Fredrickson, Executive Vice President, Oncology Haematology Business Unit, AstraZeneca.

Safety Profile Consistent with Known Profile

The safety and tolerability of Calquence were consistent with its established safety profile, and no new safety signals were identified in the AMPLIFY trial.

Regulatory Review in Other Countries

Regulatory applications for these treatment regimens are currently under review in several countries, based on the promising results from the AMPLIFY trial.

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.

References

Brown J, et al. Fixed-duration acalabrutinib combinations in untreated chronic lymphocytic leukemia. NEJM. 2025;392:748-762.
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.
AstraZeneca 2024. Full Year and Q4 2024 Financial Results Epidemiology Spreadsheet. Available at: https://www.astrazeneca.com/investor-relations.html. Accessed May 2025.
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.
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.
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.
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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