Dr. O'Brien on the Phase III ASCEND Trial in CLL

Susan M. O'Brien MD
Published: Sunday, Jun 16, 2019



Susan M. O’Brien, MD, associate director for Clinical Services, Chao Family Comprehensive Cancer Center, University of California Irvine Medical Center, discusses the phase III ASCEND trial in chronic lymphocytic leukemia (CLL).

Two next-generation BTK inhibitors are currently being investigated in clinical trials: acalabrutinib (Calquence) and zanubrutinib (BGB-311), says O’Brien. Both of these therapies, like ibrutinib (Imbruvica), are potent against BTK, but the half maximal inhibitory concentration, or IC50, for other kinases that ibrutinib inhibits is much higher with these second-generation therapies. It is believed, explains O’Brien, that this fact could reduce the toxicities associated with BTK inhibition in chronic lymphocytic leukemia, such as platelet dysfunction and atrial fibrillation.

The ASCEND trial, which was a global, randomized, multicenter, open-label phase III study, randomized 310 patients to receive either acalabrutinib monotherapy or rituximab plus the physician’s choice of either idelalisib (Zydelig) or bendamustine. The study met its primary endpoint of progression-free survival as assessed by an independent review committee.

The trial results are encouraging, says O’Brien, and will hopefully lead to the first approval for acalabrutinib in CLL. The drug has previously been approved to treat patients with relapsed mantle cell lymphoma, she concludes.

  <<< 2019 European Hematology Association Congress


Susan M. O’Brien, MD, associate director for Clinical Services, Chao Family Comprehensive Cancer Center, University of California Irvine Medical Center, discusses the phase III ASCEND trial in chronic lymphocytic leukemia (CLL).

Two next-generation BTK inhibitors are currently being investigated in clinical trials: acalabrutinib (Calquence) and zanubrutinib (BGB-311), says O’Brien. Both of these therapies, like ibrutinib (Imbruvica), are potent against BTK, but the half maximal inhibitory concentration, or IC50, for other kinases that ibrutinib inhibits is much higher with these second-generation therapies. It is believed, explains O’Brien, that this fact could reduce the toxicities associated with BTK inhibition in chronic lymphocytic leukemia, such as platelet dysfunction and atrial fibrillation.

The ASCEND trial, which was a global, randomized, multicenter, open-label phase III study, randomized 310 patients to receive either acalabrutinib monotherapy or rituximab plus the physician’s choice of either idelalisib (Zydelig) or bendamustine. The study met its primary endpoint of progression-free survival as assessed by an independent review committee.

The trial results are encouraging, says O’Brien, and will hopefully lead to the first approval for acalabrutinib in CLL. The drug has previously been approved to treat patients with relapsed mantle cell lymphoma, she concludes.

  <<< 2019 European Hematology Association Congress

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