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 MTD 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 16th Annual Discovery on Target – Targeting Tumor Myeloid Cells Meeting in September 2018. Based on an expanded data set of 163 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 20% 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 (19% overall response rate (ORR), n=21), peripheral T-cell lymphoma, or PTCL (25% ORR, n=12), and diffuse large B-cell lymphoma, or DLBCL (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 beyond 0.2 mg/kg is currently ongoing, and doses of 0.5 mg/kg have been well tolerated for up to 27 weeks.