Health Canada authorizes fixed-duration Calquence® in combination with venetoclax as a first-line treatment for patients with chronic lymphocytic leukemia

Approval based on Phase III AMPLIFY results, demonstrating a statistically significant improvement in progression-free survival for fixed-duration Calquence plus venetoclax vs. chemoimmunotherapy

MISSISSAUGA, ON – September 12, 2025 – Health Canada has granted a Notice of Compliance (NOC) for Calquence® (acalabrutinib tablets) in combination with venetoclax for adult patients with previously untreated chronic lymphocytic leukemia (CLL).1 This approval provides an all-oral, fixed-duration treatment option to patients.

“Chronic lymphocytic leukemia is the most common type of adult leukemia, and newly diagnosed patients often face the prospect of long-term, continuous oral therapy,” said Dr. Carolyn Owen, MD, FRCPC, Alberta Health Services, Calgary. “Today’s announcement marks an important milestone, offering patients an effective, well-tolerated, all-oral treatment that can be completed within a defined timeframe. This approach may help reduce the risk of long-term side effects and allow patients the opportunity to move forward with their lives beyond continuous treatment.”

The approval of Calquence in combination with venetoclax was granted based on the results from the Phase III AMPLIFY trial, which was published in The New England Journal of Medicine in February 2025.2 Results from the AMPLIFY trial showed 76.5% of patients treated with Calquence plus venetoclax were progression free at three years, versus 66.5% 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 the Calquence and venetoclax combination 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).1 The estimated 36-month overall survival rate was 94.1% in the Calquence plus venetoclax arm versus 85.9% in the chemoimmunotherapy arm.

"The combination of acalabrutinib plus venetoclax provides patients with an effective, time-limited treatment that does not require multiple hospital visits and does not require a patient to stay on drugs for many years," says Raymond Vles, Board Chair, CLL Canada. “Today’s announcement provides a welcome new option for patients, particularly for those for whom regular hospital visits are difficult due to work or family obligations, mobility issues or, for rural Canadians, the distance from their home."

The safety profile of Calquence with the addition of venetoclax was consistent with the established profiles of the individual medicines. The most common adverse reactions of any grade reported (>5%) in the Calquence plus venetoclax arm were infection (51%), leukopenia (37%), neutropenia (37%), headache (35%), diarrhea (33%), musculoskeletal pain (24%), bruising (21%), nausea (15%), fatigue (15%), arthralgia (13%), rash (12%), hemorrhage/hematoma (9%), abdominal pain (8%), constipation (7%), anemia (7%) and thrombocytopenia (6%).

CLL is a type of cancer that affects B lymphocytes (a type of white blood cell that fights infections and is found in the blood, bone marrow, lymph nodes or spleen), impacting their ability to function normally.3 Many people with CLL do not have any symptoms upon diagnosis, and the disease is often found in blood tests for unrelated health problems.4,5 More than 2,000 people in Canada per year are diagnosed with CLL, and while it most often progresses slowly over months or years, it can also be fast growing.3,6,7 B-cell receptor signalling through BTK is one of the essential growth pathways for CLL.8 The fixed-duration regimen of Calquence plus venetoclax is the first and only all-oral combination treatment option with a second-generation BTK inhibitor approved in Canada.

About the AMPLIFY Trial

AMPLIFY is a randomized, 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. Patients were randomized 1:1:1 to receive either Calquence plus venetoclax, or Calquence plus venetoclax and obinutuzumab for a fixed duration, or standard-of-care chemoimmunotherapy.2 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 (each 28 days).2 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.2 Other key secondary endpoints include overall survival and undetectable measurable residual disease.2 The trial includes 27 countries across North and South America, Europe, Asia and Oceania, including eight centres in Canada.10

About Calquence

Calquence is a second-generation, highly selective inhibitor of Bruton’s tyrosine kinase (BTK).9 Calquence binds covalently to BTK, thereby inhibiting its activity. In B-cells, BTK signalling results in activation of pathways necessary for B-cell proliferation, trafficking, chemotaxis and adhesion.9

In Canada, Calquence (acalabrutinib tablets) is approved in combination with venetoclax for patients with previously untreated CLL; as monotherapy or in combination with obinutuzumab for patients with previously untreated CLL; as monotherapy for the treatment of patients with CLL who have received at least one prior therapy; in combination with bendamustine and rituximab for patients with previously untreated MCL who are ineligible for autologous stem cell transplant; and as monotherapy for the treatment of patients with MCL who have received at least one prior therapy.

About AstraZeneca

AstraZeneca is a global, science-led biopharmaceutical company that focuses on the discovery, development, and commercialization of prescription medicines in oncology, rare diseases, and biopharmaceuticals, including cardiovascular, renal & metabolic, and respiratory & immunology. In Canada, the company employs more than 2,400 people and was recently named one of Canada’s Top 100 Employers for the second consecutive year. Together, AstraZeneca’s R&D Hub and the Alexion Rare Disease R&D Hub – both based in Mississauga, Ontario – are involved in more than 150 global clinical studies in areas such as breast, lung and prostate cancer, COPD, chronic kidney disease, and rare disease. Visit www.astrazeneca.ca for more information. 

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Contact:

AstraZeneca Canada
Email: corporatecommunications@astrazeneca.com

References:

  1. AstraZeneca Canada Inc., Calquence® (acalabrutinib tablets), Product Monograph. September 2025.
  2. Brown, J., et al. Fixed-Duration Acalabrutinib Combinations in Untreated Chronic Lymphocytic Leukemia. N Engl J Med. 2025;392:748-762. Accessed August 2025. Available at: https://www.nejm.org/doi/full/10.1056/NEJMoa2409804 
  3. Lymphoma & Leukemia Society of Canada. Chronic Lymphocytic Leukemia. Accessed August 2025. Available at: https://www.bloodcancers.ca/sites/default/files/2022-11/2022%20LLSC%20fact%20sheet_CLL_EN.pdf 
  4. Canadian Cancer Society. Symptoms of leukemia. Accessed August 2025. Available at: https://cancer.ca/en/cancer-information/cancer-types/chronic-lymphocytic-leukemia-cll/signs-and-symptoms 
  5. Canadian Cancer Society. Diagnosis of leukemia. Accessed August 2025. Available at: https://cancer.ca/en/cancer-information/cancer-types/chronic-lymphocytic-leukemia-cll/diagnosis 
  6. Owen, C., et al. Canadian evidence-based guideline for frontline treatment of chronic lymphocytic leukemia: 2022 update. Leukemia Research. 2023. Accessed August 29, 2025. Available at: https://www.sciencedirect.com/science/article/pii/S0145212623000012#bib1 
  7. Canadian Cancer Society. What is chronic lymphocytic leukemia? Accessed August 2025. Available at: https://cancer.ca/en/cancer-information/cancer-types/chronic-lymphocytic-leukemia-cll/what-is-chronic-lymphocytic-leukemia#:~:text=The%20types%20of%20leukemia%20are,cells%2C%20including%20cancer%20cells). 
  8. Schmid VK, Hobeika E. B cell receptor signaling and associated pathways in the pathogenesis of chronic lymphocytic leukemia. Front Oncol. 2024 Feb 26;14:1339620. Available at: https://pmc.ncbi.nlm.nih.gov/articles/PMC10926848/ 
  9. 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). Accessed August 2025. Available at: https://clinicaltrials.gov/study/NCT03836261?cond=Chronic%20Lymphocytic%20Leukemia,%20CLL&term=AMPLIFY&rank=1#locations