The CALAVI clinical trial is being initiated to explore the potential of acalabrutinib to treat exaggerated immune response, or cytokine storm, in patients who are severely ill with coronavirus disease 2019, according to a press release from the developer, AstraZeneca.
Louis M. Staudt, MD, PhD
The CALAVI clinical trial is being initiated to explore the potential of acalabrutinib (Calquence) to treat exaggerated immune response, or cytokine storm, in patients who are severely ill with coronavirus disease 2019 (COVID-19), according to a press release from the developer, AstraZeneca.
Strong scientific evidence supports the hypothesis that Bruton’s tyrosine kinase (BTK) inhibition, as with acalabrutinib, can reduce the production of inflammatory cytokines that are associated with respiratory complications of COVID-19. Early clinical data has also shown that reduced inflammation from acalabrutinib can lessen the severity of respiratory distress from COVID-19.
The company believes that treatment with acalabrutinib would result in a reduced need for assisted ventilation and decreased mortality rates from life-threatening symptoms of the infection.
“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,” Louis M. Staudt, MD, PhD, chief of the Lymphoid Malignancies Branch at the National Cancer Institute (NCI), said in a statement.
CALAVI will be a large, randomized, open-label, global, 2-part trial investigating the safety and efficacy of acalabrutinib added to best supportive care alone in patients hospitalized due to respiratory complications from the infection. Part 1 will evaluate patients that are not in the intensive care unit and will include a 2:1 randomization to either acalabrutinib plus best supportive care or best supportive care alone. Part 2 will focus on the combination in patients who are in the intensive care unit and have more severe respiratory complications.
The trial is expected to begin enrolling patients soon at multiple sites in the United States and across Europe. Wyndham H. Wilson, MD, PhD, head of the Lymphoma Therapeutics Section at the NCI, will serve as the principal investigator of the CALAVI trial, and Staudt will be a senior investigator in the trial as well. Primary outcome measures of the trial will focus on the use of assisted ventilation or death.
“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,” said José Baselga, MD, PhD, executive vice president, Oncology Research & Development, AstraZeneca, in a press statement.
It has been suggested that BTK-dependent macrophage signaling may play a role in the exaggerated inflammatory responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) as well COVID-19related pneumonia.
Acalabrutinib is a second-generation selective BTK inhibitor that binds covalently to BTK. The agent os approved for the treatment of adult patients with chronic lymphocytic leukemia or small lymphocytic lymphoma, and for adult patients with previously treated mantle cell lymphoma.
AstraZeneca initiates CALAVI clinical trial with Calquence against COVID-19 [press release]. AstraZeneca: April 14, 2020.https://bit.ly/2yaUq8O. Accessed April 14, 2020.