Acalabrutinib Demonstrates Non-Inferior PFS and Improved Safety Profile Compared to Ibrutinib in Head-to-Head Phase III ELEVATE-RR Trial for High-Risk Relapsed/Refractory CLL

January 25,AstraZenecaThe official website shows that Calquence (acalabrutinib) is used to treat previously treated high-risk chronic lymphocyticLeukemiaThe Phase III ELEVATE-RR study in adult patients with chronic lymphocytic leukemia (CLL) met its primary endpoint, demonstrating non-inferiority of progression-free survival compared to ibrutinib. The ELEVATE-RR study is the first Phase III clinical trial to conduct a head-to-head comparison of the efficacy of two Bruton’s tyrosine kinase (BTK) inhibitors in patients with CLL, the most common type of leukemia in adults.

The study also met the key secondary endpoint, with patients in the Calquence group experiencing atrial fibrillation compared to those in the ibrutinib group.Adverse ReactionsLower incidence (atrial fibrillation is a common type of arrhythmia; in patients with atrial fibrillationStroke...significantly increased risk of heart failure and other cardiac-related complications). Further stratified analysis results showed no difference between the two groups in the incidence of Grade 3 or higher infections or Richter’s transformation (transformation of CLL into another aggressive lymphoma). The Calquence group demonstrated a numerical trend toward benefit in OS (overall survival). Overall, the safety and tolerability profile of Calquence was consistent with its previous clinical development programs.The ELEVATE-RR (ACE-CL-006) study is a randomized, multicenter, open-label Phase III study designed to evaluate the efficacy of Calquence versus ibrutinib in patients with previously treated chronic lymphocytic leukemia (CLL) featuring high-risk characteristics (deletion 17p and/or deletion 11q). A total of 533 subjects were randomized into two groups to receive either Calquence (100 mg twice daily) or ibrutinib (420 mg once daily) until disease progression or unacceptable toxicity. The primary endpoint was PFS (progression-free survival) assessed by an independent review committee (non-inferiority, based on 250 events). Secondary endpoints included the incidence of atrial fibrillation, treatment-related Grade 3 or higher infections, Richter’s transformation, and overall survival.CLL is the most common type of leukemia in adults, with an estimated 114,000 new cases globally in 2017. With improvements in treatment modalities, the survival of CLL patients has been significantly prolonged. Excessive bone marrow hematopoiesis in the blood of CLL patients...Stem Cellstransform into abnormal lymphocytes, which are less capable of fighting infections. As the number of these abnormal cells increases, the survival space for healthy white blood cells, red blood cells, and platelets becomes increasingly limited, leading toAnemia, infection, and bleeding. Activation of BTK signaling is one of the essential pathways for B-cell proliferation, trafficking, chemotaxis, and adhesion. Calquence is a next-generation selective BTK inhibitor that suppresses BTK activity through covalent binding.

Calquence was first approved for marketing in the United States in October 2017 for the treatment of mantle cell lymphoma (MCL). In November 2019, it received approval in the US for two new indications: the treatment of chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL). In November 2020, Calquence was approved for marketing in the European Union for the treatment of adult CLL. According to the NextPharma database by PharmCube, Calquence’s global sales in 2019 amounted to $164 million.

TumorJosé Baselga, Executive Vice President of Research and Development, stated, “After 40 months of follow-up, today’s study results confirm that the selective BTK inhibitor Calquence demonstrates superior safety in terms of atrial fibrillation, and its efficacy is non-inferior to ibrutinib. All data from this study lead us to believe that Calquence can bring greater benefits to patients with CLL.”BioValleyBioon.com）