Introduction:
This abstract focuses on the activity of BI-1808, a monoclonal antibody targeting TNFR2, in patients with cutaneous T-cell lymphoma (CTCL). TNFR2 overexpression on malignant CD4+CD26- T-cells points to its possible implication in the pathogenesis of CTCL. BI-1808 inhibits the interaction between TNFR2 and its ligand TNF-α, resulting in the depletion of regulatory T cells (Tregs) through FcγR mechanisms and promoting the expansion of intratumoral CD8+ T cells. This novel approach reveals a potential new treatment for CTCL.
Methods and objectives:
The safety and preliminary efficacy of BI-1808 as a single agent are currently being investigated in patients with T-cell lymphomas, including CTCL, in the ongoing Phase 2a trial 19-BI-1808-01. Advanced mycosis fungoides (MF) and Sézary syndrome (SS) who have previously failed or progressed on systemic therapy are enrolled.
Results:
As of Oct 15, 2024, 6 subjects with CTCL received BI-1808 as single-agent Q3W. All treatment related adverse events were classified as a mild or moderate with no grade ≥ 3 AE reported.
Of 4 evaluable heavily pre-treated patients, 3 (1 MF, 2 SS) exhibited Partial Response (PR) and 1 patient showed Stable Disease by mSWAT (modified severity-weighted assessment tool). Immunofluorescence multiplex staining of skin biopsies revealed extensive CD8+ T cell infiltration and elevated granzyme B levels at five weeks post-treatment initiation.
Conclusions
Clinical data of BI-1808 in advanced CTCL show promising efficacy and evidence of immune activation.
