ONO/GS-4059, a selective BTK inhibitor, induced clinically durable responses in relapsed/refractory B-cell malignancies, including mantle cell lymphoma and chronic lymphocytic leukemia (CLL), without significant toxicities, a recent study published online ahead of print in the journal Blood has shown.1

For the multicenter, phase 1 study, researchers enrolled 90 patients with relapsed/refractory B-cell malignancies to evaluate activity, tolerability, and dose escalation of ONO/GS-4059. Patients received the drug at doses ranging from 20 mg once daily to 600 mg once daily, as well as 240 mg twice daily and 300 mg twice daily.

Results showed that 96% of evaluable patients with CLL responded to ONO/GS-4059, with a median treatment duration of 80 weeks. Of the 24 patients, 21 remain on treatment at the time of this analysis. Researchers also found that lymph node responses were rapid and associated with concurrent lymphocytosis in most patients.

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Of the 12 evaluable patients with mantle cell lymphoma, 92% responded to treatment, with a median treatment duration of 40 weeks. Of those, 8 remain on treatment. About one-third of patients with non-germinal center B-cell diffuse large B-cell lymphoma responded as well, but median treatment duration was only 12 weeks.

In regard to safety, 75% of adverse events were grade 1 or 2. Grade 3 or 4 adverse events were mostly hematologic and recovered spontaneously during ongoing treatment.

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“These patients were confronted with a cruel reality: they had failed multiple chemotherapy lines and there were no other treatment options available for them. This drug has changed their lives; from desperate and tired they are now leading a normal and really active life. This is hugely rewarding and encouraging,” Harriet Walter, MD, from the Department of Cancer Studies at the University of Leicester in England said.2

The authors note that the selectivity of ONO/GS-4059 may be more beneficial in combination therapies.


  1. Walter HS, Rule SA, Dyer MJS, et al. A phase I clinical trial of the selective BTK inhibitor ONO/GS-4059 in relapsed and refractory mature B-cell malignancies [published online ahead of print November 5, 2015]. Blood. doi: 10.1182/blood-2015-08-664086.
  2. World first blood cancer drug trial reveals life-changing results. EurekAlert! November 11, 2015. http://www.eurekalert.org/pub_releases/2015-11/uol-wfb111115.php. Accessed November 13, 2015.