TG-1701, A selective Bruton Tyrosine Kinase (BTK) Inhibitor, as monotherapy and in combination with ublituximab and umbralisib (U2) in patients with B- Cell malignancies.

Abstract

TG-1701 is a selective, covalent BTK inhibitor administered once daily (QD). Both the "U2" combination (anti-CD20 mAb ublituximab + the PI3Kδ-CK1ϵ inhibitor umbralisib) and BTK inhibition are highly active in treatment-naïve (TN) and relapsed/refractory (R/R) CLL, each having previously demonstrated superiority over standard chemoimmunotherapy. Patients with R/R CLL, MCL and Waldenstrom's (WM) were enrolled in an ongoing Ph1 study initially evaluating dose escalation (DE) of oral TG-1701 QD continuously administered in 28-day cycles (100, 200, 300, and 400 mg). After characterizing the safety profile of TG-1701 monotherapy, we implemented a parallel DE arm of TG-1701+U2. Select dose levels of TG-1701 monotherapy were expanded. All patients were treated until disease progression, unacceptable toxicity, or investigator/ patient decision to withdraw. TG-1701 exhibits an encouraging safety and efficacy profile. The combination of 1701+U2 has been well tolerated and dose escalation continues. The combination shows enhanced depth of response over TG-1701 monotherapy. Recruitment to this study (NCT03671590) continues.