Background: T-cell lymphomas (TCL) make up about 10-15% of all Non-Hodgkin's Lymphomas (NHLs), with peripheral T-cell lymphoma (PTCL) and cutaneous T-cell lymphoma (CTCL) being the main types. PTCLs are nodal or systemic T-cell lymphomas, whereas CTCL originates in the skin and includes mycosis fungoides (MF) and Sézary syndrome (SS). Survival is poor in PTCL, advanced MF as well in SS, with a 5-year survival range of 20–60%.

TNFR2 is a potential oncogene in TCL, characterized by recurrent point mutations and gain of function alterations, leading to its abnormal expression on CD4+CD26- tumor cells1. BI-1808 is an IgG1 monoclonal antibody that targets TNFR2. It inhibits TNFR2 interaction with the ligand TNF-α, enabling FcγR-dependent depletion of regulatory T cells (Treg), and promoting the expansion of intratumoral CD8+ T cells. BI-1808 has shown single agent activity in CTCL, PTCL, and solid tumor patients. Consequently, targeting TNFR2 constitutes a promising and innovative cancer treatment for patients.

Methods: Safety and preliminary efficacy of BI-1808 as single agent is currently investigated in patients with T-cell lymphomas in a sub-cohort of the ongoing Phase 2a clinical trial 19-BI-1808-01.

The study is designed to enroll 20 patients at signal seeking dose, whereafter a dose optimization phase will open.

Results: We report here the outcome of the signal seeking portion of the study. As of August 4 2025 the signal-seeking portion of the study has been fully enrolled. 19 patients with CTCL and 2 patients with PTCL received BI-1808 as single-agent Q3W. 6 female and 15 male patients, with a median age of 69,5 y (28-77), received a median of four cycles administered (range 1-19). In CTCL, 11 classified as MF (stage IIIA/IIB) and 8 as SS (stage IV), with a median of 5 (2-10) prior systemic treatments.

All treatment related adverse events were classified as mild or moderate with no potentially related Gr3+ AE reported. Disease “flares” characterized by increased skin peeling, erythema, and pruritis) were observed during the first weeks of treatment in several cases, considered related to immune activation associated with depletion of T reg and influx of CD8+ T cells. Immunofluorescence multiplex staining of skin biopsies showed evidence of significant increase in CD8+ infiltration and accompanying granzyme B elevation at 5 weeks after start of treatment.

Out of 9 CTCL evaluable cases, 1 SS patient exhibited complete response (CR) 4 participants (3 MF, 1 SS) exhibited partial response (PR) as best clinical response; the remaining 4 participants showed stable disease (SD). Out of 2 evaluable PTCL patients (both stage IV), 1 patient showed SD as best clinical response, while the other patient exhibited a substantial PR at first assessment. More complete data will be disclosed in poster

Conclusions: Current data from the signal seeking cohort of BI-1808 in TCL show promising efficacy associated with strong immune activation in patients with advanced CTCL, leading to an objective response rate of 46% and a 100% disease control rate in the evaluable population, warranting the study to proceed to next stage of dose optimization.

1Ungewickell et al Nat Genet. 2015

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2025
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