AstraZeneca’s Calquence Plus Venetoclax Approved In US Based On Phase III AMPLIFY Trial Results, As First Fixed-Duration Oral Regimen For Chronic Lymphocytic Leukaemia (CLL) And Small Lymphocytic Lymphoma (SLL)

AstraZeneca announced that Calquence (acalabrutinib) in combination with venetoclax has received approval in the United States as the first all-oral, fixed-duration treatment regimen for adults with chronic lymphocytic leukaemia (CLL) and small lymphocytic lymphoma (SLL). The decision marks an important milestone in first-line therapy, offering patients a chemotherapy-free option that can be completed within a defined treatment period.

Jennifer 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 AMPLIFY trial, said: “The continuous regimens frequently used to treat chronic lymphocytic leukaemia often come with side effects that may become burdensome to patients over time. The US approval of the Calquence combination offers patients an all-oral, 14-month, fixed-duration treatment option that is highly effective and well-tolerated, and gives physicians greater flexibility to tailor treatment plans for individual patient needs and goals.”

The approval from the U.S. Food and Drug Administration is supported by results from the Phase III AMPLIFY trial. Findings were presented at the American Society of Hematology 2024 Annual Meeting and published in The New England Journal of Medicine. In the study, 77% of patients treated with Calquence plus venetoclax remained progression-free at three years, compared with 67% of those receiving standard chemoimmunotherapy (fludarabine-cyclophosphamide-rituximab or bendamustine-rituximab). Median progression-free survival was not reached in the combination arm, versus 47.6 months for chemoimmunotherapy.

Dave Fredrickson, Executive Vice President, Oncology Haematology Business Unit, AstraZeneca, said: “Today’s approval delivers the first all-oral, fixed-duration BTK inhibitor-based regimen in the US for the treatment of chronic lymphocytic leukaemia. This Calquence combination has the potential to meaningfully change 1st-line chronic lymphocytic leukaemia treatment decisions and underscores our commitment to improving on the current standard of care for people living with blood cancers.”

The combination reduced the risk of disease progression or death by 35% compared to standard treatment (hazard ratio 0.65; p=0.0038). CLL is the most common form of leukaemia in adults, with approximately 18,500 patients treated in the first-line setting in the US in 2024. The availability of a fixed-duration oral regimen provides a new alternative to traditional chemotherapy-based approaches.

Gwen Nichols, MD, Chief Medical Officer of Blood Cancer United, formerly The Leukemia & Lymphoma Society, said: “Managing an incurable blood cancer that progresses slowly can often feel indefinite and overwhelming. We welcome new treatment options that may ease the burden, restore a sense of control and offer renewed hope for those navigating life with chronic lymphocytic leukaemia.”

Calquence plus venetoclax has also been approved in the European Union, Canada, the United Kingdom and several other markets, with additional regulatory reviews ongoing. The safety profile of Calquence in the combination regimen was consistent with previous studies, and no new safety concerns were identified.