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ASH 2021 | TG-1701, a novel BTKi, in B-cell malignancies

Chan Yoon Cheah, MBBS, Linear Clinical Research and Sir Charles Gairdner Hospital, Perth, Australia, describes results from the ongoing Phase I trial (NCT03671590) of TG-1701, a Bruton’s tyrosine kinase (BTK) inhibitor, in patients with chronic lymphocytic leukemia (CLL) and non-Hodgkin lymphoma (NHL). Patients received either TG-1701 as monotherapy, or with ublituximab and umbralisib. TG-1701 has a promising safety and efficacy profile, and patients who received lower doses of the triplet combination reported fewer adverse events. This interview took place at the 63rd ASH Annual Meeting and Exposition congress in Atlanta, GA.

Transcript (edited for clarity)

TG-1701 is a covalent Bruton’s tyrosine kinase inhibitor. And we’ve been doing this study for a few years now, and in fact, we have presented the data at meetings every six to 12 months or so. The ASH data is new in the sense that we’ve included a cohort of patients treated with a lower dose regimen in a combination with umbralisib, which is a PI-3 kinase and CK1 epsilon inhibitor, and also ublituximab, which is an anti CD-20 monoclonal antibody...

TG-1701 is a covalent Bruton’s tyrosine kinase inhibitor. And we’ve been doing this study for a few years now, and in fact, we have presented the data at meetings every six to 12 months or so. The ASH data is new in the sense that we’ve included a cohort of patients treated with a lower dose regimen in a combination with umbralisib, which is a PI-3 kinase and CK1 epsilon inhibitor, and also ublituximab, which is an anti CD-20 monoclonal antibody.

So TG-1701 has activity in the range of B-cell malignancies in which you would expect it to. And other data certainly confirmed this with response rates of 95 to 100% in CLL, 71% in mantle cell lymphoma, 95% in Waldenstrom’s Macroglobulinemia. The interesting thing about this new presentation in ASH is the expansion of the triplet combination, where we have 100 milligrams of TG-1701, which is half the monotherapy dose, and 400 milligrams of umbralisib which is again, half the monotherapy dose.

We found when we did the triple combination with the full dose of those agents that we did see quite a bit of toxicity in terms of neutropenia. We saw fatigue, we saw bruising, we saw nausea and we saw abnormalities in the liver function tests.

When we treated a further 33 patients at the lower dose level, so in other words half dose of both the BDK and the PI-3 kinase inhibitor, the adverse event profile cleaned up nicely. And we saw very few of those things. The caveat here is that we only have three months of follow up. So a longer period of observation is needed, but it certainly looks like that may be the go-to dose for this triple combination, particularly because efficacy was preserved with a response rate of exceeding 80%. And at this stage not appearing any different from the full dose combination.

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