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Novel BTK Inhibitor Alone or in Combination With Ublituximab and Umbralisib in CLL

By: Lauren Harrison, MS
Posted: Friday, February 4, 2022

TG-1701, a novel, irreversible Bruton’s tyrosine kinase inhibitor, appears to be both safe and active when used alone and in combination with the anti-CD20 monoclonal antibody ublituximab and the PI3Kδ inhibitor umbralisib among patients with chronic lymphocytic leukemia (CLL). The results of this phase I study were presented by Chan Yoon Cheah, MBBS, DMSc, of the University of Western Australia in Crawley, Australia, at the 2021 American Society of Hematology (ASH) Annual Meeting & Exposition (Abstract 1549).  

This study enrolled 142 patients with either CLL or non-Hodgkin lymphoma. Patients were treated with TG-1701 monotherapy (n = 106) or TG-1701 plus ublituximab and umbralisib (n = 36), with dose escalation of TG-1701 as tolerated. Patients were treated until disease progression, unacceptable toxicity, or patient/provider decision to withdraw.

In the monotherapy CLL-specific cohorts, 40 patients could be evaluated for safety and 39, for efficacy. The overall response rate was 97%, with consistent response rates among all subgroups. In addition, 19 patients were evaluable for safety and efficacy of TG-1701 plus ublituximab and umbralisib. The overall response rate was 84%, and 17 other patients were awaiting postbaseline assessment. The median duration of response has not yet been reached in either cohort.

The most common treatment-emergent adverse events in the monotherapy group were elevated liver transaminase levels (18% all grades), diarrhea (15%), and neutropenia (13%). One patient had an adverse event leading to a dose reduction. There were no cases of atrial fibrillation, major bleeding, or ventricular tachyarrhythmia in the CLL cohorts.

In the combination-therapy group, the most common any-grade treatment-emergent adverse events were diarrhea (53%), contusion (42%), nausea (37%), hypertension (32%), increased transaminase levels (32%), and fatigue (32%). The sole grade 3 or 4 adverse event that occurred with a high frequency was an elevated liver transaminase level (21%). One patient in this group underwent dose reduction secondary to adverse events, and four patients discontinued at least one of the study drugs.

Disclosure: For a full list of authors’ disclosures, visit ash.confex.com


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