AstraZeneca’s Calquence (acalabrutinib) hit the mark in a Phase III trial of previously-treated patients with chronic lymphocytic leukemia (CLL). The positive data marked Calquence as the first Bruton tyrosine kinase (BTK) inhibitor to show a benefit in CLL as a monotherapy.

AstraZeneca stopped the trial early after Calquence hit its endpoint at an interim analysis. Phase III results from the ASCEND trial showed that Calquence demonstrated a statistically significant and clinically meaningful improvement in progression-free survival (PFS) compared to a combination regimen of rituximab plus physician’s choice of idelalisib or bendamustine. In B-cells, BTK signaling results in activation of pathways necessary for B-cell proliferation, trafficking, chemotaxis, and adhesion.

AstraZeneca remained mum with the full data readout of the trial. The trial’s primary endpoint is progression-free survival assessed by an independent review committee. Key secondary endpoints include physician-assessed PFS, IRC- and physician-assessed overall response rate and duration of response, as well as overall survival, patient-reported outcomes and time to next treatment. The safety and tolerability of Calquence were consistent with the known profile, AstraZeneca added. The company intends to share the data at a future medical conference, likely ASCO at the end of this month in Chicago.

“Calquence is the first BTK inhibitor to show benefit in a Phase III trial as a monotherapy compared to current standard-of-care combinations used in relapsed or refractory chronic lymphocytic leukemia. We look forward to presenting detailed results at a forthcoming medical meeting.” José Baselga, AstraZeneca’s head of R&D Oncology said in a statement.

Calquence is currently approved for the treatment of adults with relapsed or refractory mantle cell lymphoma (MCL) and is being developed for the treatment of CLL and other blood cancers. ASCEND is the first of two Phase III trials in CLL with Calquence that are expected to read out this year. The second trial is ELEVATE-TN in treatment-naïve front-line CLL. Calquence is being developed for the treatment of multiple B-cell blood cancers including CLL, MCL, diffuse large B-cell lymphoma, Waldenstrom macroglobulinaemia, follicular lymphoma and multiple myeloma.

When Calquence was first approved in 2017, AstraZeneca Chief Executive Officer Pascal Soriot said the drug would become a cornerstone in the company’s hematology pipeline.

AstraZeneca isn’t the only company to aim its resources at CLL. In March, AbbVie’s venetoclax won Breakthrough Therapy Designation from the U.S. Food and Drug Administration in CLL. Venetoclax, in combination with obinutuzumab, is being investigated as a solution for untreated adult patients with chronic lymphocytic leukemia. The designation coincides with the completion of the supplemental New Drug Application submission to the FDA for approval in previously-untreated CLL patients. Approval for the combination treatment could come quickly, as the FDA will review the drug under its Real-Time Oncology Review pilot program that is aimed to speed up the approval process.



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