AstraZeneca will initiate a randomised, global clinical trial to assess the potential ofCalquence(acalabrutinib) in the treatment of the exaggerated immune response (cytokine storm) associated with COVID-19 infection in severely ill patients.

The trial design is based upon strong scientific evidence supporting the role of the Bruton’s tyrosine kinase (BTK) pathway in the production of inflammatory cytokines and on encouraging early clinical data.Calquenceis a next-generation, highly selective BTK inhibitor currently used to treat certain types of blood cancers.

Calquenceis a next-generation, selective inhibitor of BTK.Calquencebinds covalently to BTK, thereby inhibiting its activity.9,10,11,12In B-cells, BTK signalling results in activation of pathways necessary for B-cell proliferation, trafficking, chemotaxis, and adhesion.13

Calquence(acalabrutinib) is approved for the treatment of adult patients with chronic lymphocytic leukaemia (CLL) in the US and a few other countries with an active global filing programme. In addition, Calquence is indicated for adult patients with mantle cell lymphoma (MCL) who have received at least one prior therapy in the US and several other countries.

The trial, called CALAVI, is based on early clinical data with Calquence demonstrating that a decrease in inflammation caused by BTK inhibition appears to reduce the severity of COVID-19-induced respiratory distress. The goal of the trial is to evaluate the efficacy and safety of adding Calquence to best supportive care (BSC) to reduce mortality and the need for assisted ventilation in patients with life-threatening COVID-19 symptoms.

This large, multicentre, global, randomised trial uses a two-part patient-centric design developed in record time to accelerate data capture and analysis. Part one evaluates the addition of Calquence to BSC versus BSC alone in patients hospitalised with COVID-19 who are not in the intensive care unit (ICU). Part two evaluates the addition ofCalquenceto BSC in a cohort of patients in the ICU.

José Baselga, Executive Vice President, Oncology R&D, said: “With this trial we are responding to the novel insights of the scientific community and hope to demonstrate that adding Calquence to best supportive care reduces the need to place patients on ventilators and improves their chances of survival. This is the fastest launch of any clinical trial in the history of AstraZeneca.”

Louis M. Staudt, M.D., Ph.D., Chief of the Lymphoid Malignancies Branch at the National Cancer Institute (NCI), said: “Given the well documented role of the protein BTK in regulating inflammation, it is possible that inhibiting BTK with acalabrutinib could provide clinical benefit in patients with advanced COVID-19 lung disease. As with all new treatments, it will be necessary to gather data from clinical trials in order to understand the best and safest treatment options for patients.”

The CALAVI trial is expected to open for enrolment in the coming days in the US and several countries in Europe. Wyndham H. Wilsonof NCI in the US, will serve as the principal investigator of the trial. Louis M. Staudtwill serve as senior investigator.

The trial design is based upon strong scientific evidence supporting the role of the Bruton’s tyrosine kinase (BTK) pathway in the production of inflammatory cytokines and on encouraging early clinical data.