Dual JAK/SYK inhibition in refractory NHL with cerdulatinib

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Published: 23 Jun 2017
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Dr Paul Hamlin - Memorial Sloan Kettering Cancer Center, NY, USA

Dr Hamlin speaks with ecancer at EHA 2017 about a novel dual JAK/SYK inhibitor, cerdulatinib.

He identifies an overall response rate of 50% across all patients in the trial, with responses up to 67% among those with follicular lymphoma, with manageable toxicity profile that responded to dose reduction without loss of efficacy.

Further trials are accruing patients currently.

Dr Hamlin also presented these results at a press conference session, available here.

ecancer's filming has been kindly supported by Amgen through the ECMS Foundation. ecancer is editorially independent and there is no influence over content.

I have the honour at this EHA meeting of presenting on behalf of my colleagues work that we’ve done with the phase II study exploring cerdulatinib which is an oral ATP competitive inhibitor of a number of kinases, specifically JAK1 and JAK3 as well as SYK. The study is exploring its safety and effectiveness in B-cell malignancies as well as in a cohort of T-cell lymphomas.

This is a study that was predicated on the phase I experience which confirmed both tumour activity and the ability of cerdulatinib to significantly inhibit the targets. So we can add clinically relevant doses impact on both SYK and the JAK/STAT pathway inhibiting those pathways effectively with b.i.d. dosing, so twice daily oral inhibition of those pathways is achieved. The phase II experience that will report at this meeting has demonstrated significant activity so overall in cohorts that include CLL and SLL, follicular and indolent lymphoma, aggressive lymphoma and T-cell lymphoma there has been a 50% overall response rate. They have predominantly been partial remissions with a single CR but responses are quick, after two cycles, and have been durable with about half the patients remaining on study drug and four patients approaching a year on continued therapy. What’s notable is the activity that we’ve seen in CLL SLL, with the 67% partial remission rate, some of those with lymphocytosis as we see with B-cell receptor inhibitors, and in follicular lymphoma where five out of nine patients have responded and have had durable activity. We’ve seen responses in patients who have had previous exposure to agents in similar classes like B-cell receptors and PI3 kinase inhibitors. So that’s exciting too as our patients increasingly have the need for agents that will work even when they’re refractory to other small molecule inhibitors.

Safety has been exciting, well tolerated. We’ve seen fatigue, diarrhoea and some cytopenias as a side effect profile but they’ve generally been manageable with dose reductions and in the instance of diarrhoea with antimotility agents. So the work is ongoing; the initial signals are quite attractive and pave the way for understanding what the effectiveness will be in the total cohort. We expect to hopefully complete accrual towards the end of the year in the different disease specific subtypes and there is certainly rationale for further development in the future with combinations of other agents.