AstraZeneca initiates CALAVI study of Calquence to treat cytokine storm associated with COVID-19 infection.

AstraZeneca will initiate a randomised, global clinical trial to assess the potential of Calquence (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. Calquence is a next-generation, highly selective BTK inhibitor currently used to treat certain types of blood cancers 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 of Calquence to 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. Wilson, MD, PhD, of NCI in the US, will serve as the principal investigator of the trial. Louis M. Staudt, MD, PhD will serve as senior investigator

CALAVI is a large, randomised, open-label, multicentre, global, two-part trial evaluating the efficacy and safety of Calquence with BSC versus BSC alone in patients hospitalised with respiratory complications of COVID-19. Part one is randomised (2:1) and evaluates the addition of Calquence to current BSC in patients who are hospitalised but not on assisted ventilation and not in the ICU. Part two evaluates the addition of Calquence to BSC in a cohort of patients in the ICU with more severe respiratory complications. The trial is being conducted in multiple sites around the world. The primary endpoint measures the use of assisted ventilation or death.