Safety and activity of the once daily selective Bruton Tyrosine Kinase (BTK) inhibitor TG-1701 in patients with chronic lymphocytic leukaemia (CLL) and lymphoma.

Abstract

BTK inhibition is effective in the treatment of CLL and lymphoma but requires continuous treatment and complete responses (CR) are rare. BTK based combination regimens have the potential to increase depth of response and to permit time-limited therapy. TG-1701 is a selective, once daily (QD), covalently bound BTK inhibitor.

Aims Herein we report the results of the dose-escalation study of TG-1701 as monotherapy and in combination with umbralisib and ublituximab (1701 + U2).

Methods The primary objectives of the study are to characterize the safety profile and to determine the recommended Phase 2 dose of TG-1701 and TG-1701 + U2. Other objectives: assessment of pharmacokinetics (PK), antitumor activity, and pharmacodynamics. Eligible patients (pts) have B-cell malignancy relapsed/refractory to standard therapy. Treatment consists of escalating doses of oral TG-1701 QD, continuously administered in 28-day (D) cycles (C). Pts in the TG-1701 + U2 arm receive TG-1701 + umbralisib 800 mg oral QD + ublituximab 900 mg IV on D1, 8, 15 of C1, and D1 of C2 - C6. All pts are treated until disease progression, unacceptable toxicity, or withdrawal of consent. Conclusion TG-1701, alone and in combination with U2, has an encouraging safety profile with clinical and pharmacodynamic activity at all dose levels evaluated. This study (NCT03671590) has opened enrollment in disease-specific cohorts.