12 November 2020 07:00 GMT
CALAVI did not meet the primary endpoint of increasing the proportion of patients who remained alive and free of respiratory failure
The CALAVI Phase II trials for Calquence (acalabrutinib) in patients hospitalised with respiratory symptoms of COVID-19 did not meet the primary efficacy endpoint. The addition of Calquence to best supportive care (BSC) did not increase the proportion of patients who remained alive and free of respiratory failure. No new safety signal for Calquence was observed in the trials.
José Baselga, Executive Vice President, Oncology R&D, said: “Since the beginning of the year, AstraZeneca has been committed to doing everything we can to respond to COVID-19, including investigating existing medicines as potential treatments. The CALAVI trials were launched based on preclinical and early clinical evidence that Calquence could decrease the hyperinflammatory immune response and improve clinical outcomes in patients hospitalised with respiratory symptoms of COVID-19.1 While the CALAVI results are disappointing, we remain committed to advancing science that helps patients during this unprecedented global pandemic, including clinical trials for the AstraZeneca Oxford coronavirus vaccine and our long-acting antibody combination.”
The CALAVI programme comprised two Phase II trials investigating acalabrutinib plus BSC versus BSC alone in hospitalised patients with COVID-19 disease.
The safety and tolerability profiles for Calquence in the CALAVI Phase II trials were consistent with previous trials. The data will be presented in due course.
Results from the CALAVI Phase II trials do not impact approved indications or pending approvals for Calquence in patients with blood cancers.
The CALAVI Phase II programme comprised two randomised, open-label, multicentre trials evaluating the efficacy and safety of Calquence with BSC versus BSC alone in patients hospitalised with respiratory complications of COVID-19. The trials were randomised (1:1) and evaluated the addition of Calquence to current BSC in patients who were hospitalised but not on mechanical ventilation and not in the intensive care unit. The primary endpoint measured respiratory failure or death. The trials were conducted in the US (CALAVI US) and in multiple other countries across the world (CALAVI).2,3
Calquence (acalabrutinib) is a next-generation, selective inhibitor of Bruton’s tyrosine kinase (BTK). Calquence binds covalently to BTK, thereby inhibiting its activity.4,5 In B-cells, BTK signalling results in activation of pathways necessary for B-cell proliferation, trafficking, chemotaxis, and adhesion.4
As part of an extensive clinical development programme, AstraZeneca and Acerta Pharma are currently evaluating Calquence in more than 20 company-sponsored clinical trials. Calquence is being developed for the treatment of multiple B-cell blood cancers including chronic lymphocytic leukaemia, mantle cell lymphoma, diffuse large B-cell lymphoma, Waldenström’s macroglobulinaemia, follicular lymphoma, and other haematologic malignancies.
AstraZeneca (LSE/STO/Nasdaq: AZN) is a global, science-led biopharmaceutical company that focuses on the discovery, development and commercialisation of prescription medicines, primarily for the treatment of diseases in three therapy areas - Oncology, Cardiovascular, Renal & Metabolism, and Respiratory & Immunology. Based in Cambridge, UK, AstraZeneca operates in over 100 countries and its innovative medicines are used by millions of patients worldwide. Please visit astrazeneca.com and follow the Company on Twitter @AstraZeneca.
1. Roschewski M, et al. Inhibition of Bruton tyrosine kinase in patients with severe COVID-19. Sci Immunol. 2020;5(28). DOI: 10.1126/sciimmunol.abd0110.
2. ClinicalTrials.gov. Acalabrutinib Study With Best Supportive Care Versus Best Supportive Care in Subjects Hospitalized With COVID-19. (CALAVI US). NCT identifier: NCT04380688. Available online. Accessed October 2020.
3. ClinicalTrials.gov. Acalabrutinib Study With Best Supportive Care Versus Best Supportive Care in Subjects Hospitalized With COVID-19. (CALAVI). NCT identifier: NCT04346199. Available online. Accessed October 2020.
4. Calquence® (acalabrutinib) [prescribing information]. Wilmington, DE; AstraZeneca Pharmaceuticals LP; 2019.
5. Wu J, Zhang M & Liu D. Acalabrutinib (ACP-196): a selective second-generation BTK inhibitor. J Hematol Oncol. 2016;9(21).