CALQUENCE®▼ (acalabrutinib)
mechanism of action:
how does it work?

CALQUENCE mode of action (MoA)

 

CALQUENCE (acalabrutinib) is a BTK inhibitor that offers a potent treatment for chronic lymphocytic leukaemia (CLL).1,2 In patients with B-cell malignancies dosed with acalabrutinib 100 mg twice daily, median steady-state BTK occupancy of ≥95% in peripheral blood was maintained over 12 hours, resulting in inactivation of BTK throughout the recommended dosing interval.3 The clinical relevance of these preclinical data has not been established.1

 

A second-generation, highly selective (in vitro), and potent BTK inhibitor (BTKi)1-4

 

At the recommended oral dose of 100 mg BID, CALQUENCE delivers:

  • Rapid absorption with fast BTK inhibition1,3
  • Durable efficacy with up to 6 years of follow-up data (exploratory analysis)5

CALQUENCE + venetoclax combine distinct mechanisms of action to provide a multi-targeted 1L CLL treatment with a 2nd generation BTKi6

 

Calquence and venetoclax MoA3,6-9*

 

As shown via kinome map; clinical relevance of kinome selectivity is currently unknown

CALQUENCE, a second generation BTKi, demonstrates different selectivity and limited off-target kinase activity compared with ibrutinib and zanubrutinib in vitro.

 

Calquence shows:

  • near-complete and sustained BTK occupancy within 3 hours at the recommended oral dose of 100mg twice daily1
  • selectivity for BTK with limited off-target activity1,4

 

Adapted from Kaptein, et al. 2018

The images represent the profile of acalabrutinib, ibrutinib and zanubrutinib in a competitive binding assay of more than 450 human kinases and disease-relevant mutants when tested at a single concentration of 1μM.

 

  • Less off-target activity vs ibrutinib and zanubrutinib1,2
  • The clinical relevance of these preclinical data has not been established1,2

View the AMPLIFY study

See why CALQUENCE + venetoclax is an option for your 1L CLL patients

View the ELEVATE-TN study

View our long-term data in previously untreated patients

Footnote:
*Image adapted from Timofeeva N, et al. Blood Neoplasia. 2024;1(3)100034. and obinutuzumab 1000 mg concentrate for solution for infusion SmPC.

 

Abbreviations:
1L, first line; BID, two times a day; BTK, Bruton tyrosine kinase; BTKi, Bruton tyrosine kinase inhibitor; CLL, chronic lymphocytic leukaemia; MoA, mode of action; SmPC, summary of product characteristics.

 

References:

1. Barf T, et al. J Pharmacol Exp Ther. 2017;363(2):240–252. 2.Podoll T, et al. J Pharmacol Exp Ther. 2023;384(1):173–186. 3. Calquence (acalabrutinib) 100 mg SmPC – UK. 4.  Bond DA, et al. Curr Hematol Malig Rep. 2019;14(3):197–205. 5. Sharman P, et al. Blood. 2023;142(1):636. 6. Patel K, et al. J Hematol Oncol. 2021;14(1):69. 7. Timofeeva N, et al. Blood Neoplasia. 2024;1(3):100034. 8. Genentech. Gazyva (obintuzumab) product information. Genentech Website. https://www.gene.com/media/product-information/gazyva. Accessed August 2025. 9. Deng J, et al. Leukemia. 2017;31(10):2075-2084. 10. Lu P, et al. Blood Cancer J. 2021;11(2):39. 11. Zanubrutinib 80mg hard capsules Summary of Product Characteristics.

Adverse events should be reported

Adverse events should be reported. Reporting forms and information can be found at www.mhra.gov.uk/yellowcard. Adverse events should also be reported to AstraZeneca by visiting contactazmedical.astrazeneca.com or by calling 0800 783 0033.

November 2025 I GB-69426