AstraZeneca's BTK Inhibitor Calquence Reduces Risk of Disease Progression by Nearly 70% in Relapsed/Refractory CLL, Demonstrating Superiority Over Standard Therapy

Recently, AstraZeneca announced the Phase 3 clinical trial results of the BTK inhibitor Calquence (acalabrutinib) for the treatment of relapsed/refractory (R/R) chronic lymphocytic leukemia (CLL) at the 24th European Hematology Association (EHA) Annual Congress. The trial results demonstrated that, compared with standard therapy, Calquence significantly prolonged progression-free survival (PFS) in patients.

Chronic lymphocytic leukemia (CLL) is the most common type of leukemia in adults, with approximately over 190,000 new cases diagnosed globally each year. In patients with CLL, excessive hematopoietic stem cells in the bone marrow differentiate into abnormal lymphocytes. These abnormal cells not only fail to effectively combat infections but also suppress the production of healthy white blood cells, red blood cells, and platelets, leading to anemia, infections, and bleeding. The BTK-mediated B-cell receptor signaling pathway is a critical pathway driving CLL proliferation.

Calquence is a BTK inhibitor developed by AstraZeneca that covalently binds to BTK and inhibits its activity. Calquence received accelerated approval from the U.S. FDA in 2017 for the treatment of mantle cell lymphoma (MCL).

In the randomized, open-label, global Phase 3 ASCEND trial, 310 patients received Calquence monotherapy or a combination therapy of rituximab with either idelalisib or bendamustine, as selected by the investigators.

▲PFS Data from Patients in the ASCEND Phase 3 Clinical Trial (Image source: Reference [1])

The trial results demonstrated that, at a median follow-up of 16.1 months, patients in the Calquence group achieved a statistically significant and clinically meaningful improvement in progression-free survival (PFS) compared with the active control group. Calquence reduced the risk of disease progression or death by 69% (HR, 0.31; 95% CI, 0.20–0.49; p<0.0001).

The median PFS in the Calquence group was not reached, compared to 16.5 months in the control group. After 12 months of treatment, 88% of patients in the Calquence group remained free from disease progression, versus 68% in the control group.

Dr. José Baselga, Executive Vice President of Oncology R&D at AstraZeneca, stated, “These data further support Calquence as a chemotherapy-free treatment option for CLL. Combined with the recent data from our Phase 3 clinical trial ELEVATE-TN (in treatment-naïve CLL patients), these findings will form the cornerstone of our regulatory submissions later this year.”

References:

[1] CALQUENCE® (acalabrutinib) Significantly Prolonged the Time Patients Lived without Disease Progression in Relapsed or Refractory Chronic Lymphocytic Leukemia. Retrieved June 16, 2019, from https://www.businesswire.com/news/home/20190615005011/en

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