TTI-621-01 (NCT02663518) is a multicenter, open-label phase 1a/b trial of TTI-621 in subjects with relapsed or refractory hematologic malignancies. The objectives of this study are to characterize the safety, tolerability, and pharmacokinetics of TTI-621, to determine the maximum tolerate dose or the recommended dose/regimen, and to gain preliminary evidence of the anti-tumor activity of TTI-621. In this study TTI-621 is given as a 1 hour intravenous infusion once per week. Most patients on this study receive TTI-621 as a monotherapy in a variety of different hematological malignancies; it may be administered with rituximab in patients with CD20-positive lymphoma or in combination with the PD-1 checkpoint inhibitor nivolumab in patients with Hodgkin lymphoma.
Updated clinical data were reported at the T-Cell Lymphoma Forum in January 2019. Based on an expanded data set of 179 patients, weekly infusions of TTI-621 were shown to be well tolerated. Thrombocytopenia was the most frequent grade 3 or higher treatment-emergent adverse event, occurring in 18% of patients. Platelet reductions, however, were shown to be transient and pre-dose platelet levels remained steady during the course of the study. Notably, the reversible thrombocytopenia did not lead to an increased risk of bleeding and had no impact on drug delivery, nor was there a significant impact of TTI-621 on hemoglobin levels. Monotherapy efficacy was observed in patients with mycosis fungoides (17% overall response rate (ORR), n=24), Sézary Syndrome (20% ORR, n=5) and peripheral T-cell lymphoma, or PTCL (18% ORR, n=11). As reported at the 16th Annual Discovery on Target conference in September 2018, monotherapy efficacy was also observed in DLBCL patients (25% ORR, n=8), and in DLBCL patients when combined with rituximab (25% ORR, n=24). This clinical activity was observed in patients receiving relatively low doses of drug (0.2 mg/kg for monotherapy or 0.1 mg/kg in combination with rituximab). Dose intensification to 0.5 mg/kg have been well tolerated, and the protocol was recently amended to enable dosing beyond 0.5 mg/kg.