Our lead programs, TTI-621 and TTI-622, are SIRPαFc decoy receptors designed to block the CD47 “do not eat” signal and activate both the innate and adaptive immune systems. Below please find a list of our current clinical trials.
A multicenter, open-label phase 1 trial of intratumoral TTI-621 in patients with relapsed and refractory percutaneously accessible solid tumors or mycosis fungoides (a form of cutaneous T cell lymphoma).
A multicenter, open-label phase 1a/1b trial of intravenous TTI-621 in patients with relapsed or refractory hematologic malignancies.
A two-part, multicenter, open-label, phase 1a/1b study of TTI-622 in patients with advanced relapsed or refractory lymphoma or multiple myeloma.
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TTI-621-02 (NCT02890368) is a multicenter, open-label phase 1 trial of TTI-621 in patients with relapsed or refractory percutaneously accessible solid tumors or mycosis fungoides (a form of cutaneous T cell lymphoma). In this study TTI-621 is administered directly into the tumor (intratumoral dosing). Most patients on this study receive TTI-621 as a monotherapy; for some tumor types, TTI-621 may be administered with pegylated interferon-alpha, a PD-1/PD-L1 inhibitor, an oncolytic virus or radiation. The objectives of this study are to characterize the safety and tolerability of intratumoral TTI-621, to determine the recommended dose/regimen, and to gain preliminary evidence of the anti-tumor activity of TTI-621 following local administration. Detailed evaluation of serial, on-treatment tumor biopsies of both injected and non-injected cancer lesions will help characterize tumor microenvironment changes anticipated with CD47 blockade.
The most recent data from the ongoing study were reported at the American Society of Hematology 60th Annual Meeting in December 2018. Local delivery of TTI-621 was well tolerated, with no treatment-related > Grade 3 adverse events or dose-limiting toxicity observed in 27 mycosis fungoides patients. Among 22 evaluable patients, reductions in CAILS (Composite Assessment of Index Lesion Severity) scores, which measure local lesion responses, were observed in 91% of patients, with 41% exhibiting reductions of 50% or greater. These responses occurred rapidly within the 2-week induction period. Similar CAILS scores changes were seen in adjacent non-injected lesions, suggesting locoregional effects that were not confined to the site of injection. Evidence of a systemic effect was observed in one patient receiving continuation monotherapy beyond the 2-week induction therapy. In addition, data suggest a combination effect with pegylated IFN-alpha-2a. Based on these responses, intratumoral monotherapy and combination therapy is ongoing in CTCL patients.
This study is currently recruiting patients. For more information, including a list of trial locations, please refer to clinicaltrials.gov.
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.
This study is currently recruiting patients. For more information, including a list of trial locations, please refer to clinicaltrials.gov.
TTI-622-01 (NCT03530683) is a two-part, multicenter, open-label, phase 1a/1b study of TTI-622 in patients with advanced relapsed or refractory lymphoma or multiple myeloma. In the phase 1a dose-escalation part, patients are enrolled in sequential dose cohorts to receive TTI-622 once weekly to characterize safety, tolerability, pharmacokinetics, and to determine the maximum tolerated dose. In the phase 1b part, patients will be treated with TTI-622 in combination with rituximab in CD20+ lymphoma, a proteasome inhibitor-containing regimen in multiple myeloma, or a PD-1 inhibitor in classic Hodgkin’s lymphoma. Rituximab and proteasome inhibitors may provide additional “eat” signals that could enhance the efficacy of TTI-622. A PD-1 inhibitor may help amplify any anti-tumor T cell response generated by TTI-622. The first patient was dosed with TTI-622 in June 2018.
This study is currently recruiting patients. For more information, including a list of trial locations, please refer to clinicaltrials.gov.