Subasumstat + Rituximab Is Tolerable in Subsets of Non-Hodgkin Lymphoma Patients

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07/09/23

Karuppiah Kannan, Senior Director and Global Program Leader at Takeda Pharmaceuticals, discusses early results of a phase 1/2 study evaluating subasumstat (TAK-981) in combination with rituximab in multiple subsets of CD20-positive relapsed/refractory non-Hodgkin lymphoma including diffuse large B-cell lymphoma (DLBCL), mantle cell lymphoma (MCL), follicular lymphoma (FL) and marginal zone lymphoma (MZL). The results of this study were recently presented at The American Society of Hematology Meeting & Exposition (ASH 2021).

Subasumstat is an investigational, first-in-class small-molecule inhibitor of SUMOylation, which mediates cell cycle progression. In preclinical trials, subasumstat was shown to add synergistic benefit when combined with rituximab in non-Hodgkin lymphoma models.

The phase 1/2 study is an ongoing clinical trial evaluating rituximab with increasing doses of subasumstat. The goal of the phase 1 portion is to establish safety and tolerability of subasumstat, namely the maximum tolerated dose and/or pharmacologically active dose. Data from the phase 1 portion were recently presented at ASH 2021.

As of the data cutoff, 24 patients with CD20-positive relapsed/refractory non-Hodgkin lymphoma have been enrolled and treated, and an additional four patients are currently receiving treatment. Overall, subasumstat was well tolerated across dose levels with no dose-limiting toxicities reported to date. Transient flu-like symptoms such as fever, chills, fatigue, and diarrhea were common among patients, though these adverse events are easily manageable and typical of interferon therapies. Grade ≥3 treatment-emergent adverse events related to subasumstat were reported in two patients: grade 3 atrial fibrillation and grade 4 neutropenia. Additionally, the combination of subasumstat and rituximab resulted in promising clinical activity in patients with CD20-positive relapsed/refractory non-Hodgkin lymphoma, with an overall response rate of 29%. This supports the continued development of this combination in patients with non-Hodgkin lymphoma.

The next steps for this study include: completing the phase 1 portion, establishing a recommended phase 2 dose, and opening the phase 2 expansion cohort in select indications such as DLBCL and FL.
In addition, an ongoing phase 1b/2 study is currently evaluating subasumstat in combination with monoclonal antibodies (either subcutaneous daratumumab or mezagitamab) in patients with triple-class refractory multiple myeloma. Data from this trial was also recently presented at ASH 2021.