Tidutamab (previously XmAb18087) is a bispecific antibody that engages the immune system against tumors by binding to somatostatin receptor 2 (SSTR2) and CD3. Xencor’s XmAb® Bispecific Fc Domain serves as the scaffold for these two antigen binding domains and confers long circulating half-life, stability and ease of manufacture on tidutamab. Engagement of CD3 by tidutamab activates T cells for highly potent and targeted killing of SSTR2-expressing tumor cells.
In October 2020, initial dose-escalation data from the Phase 1 study were presented at the North American Neuroendocrine Tumor Society (NANETS) symposium. Tidutamab was generally well tolerated at the recommended dose identified for the expansion portion of the study. Peripheral blood biomarkers indicated tidutamab induced acute and sustained T-cell activation at this dose, and a dose-dependent increase in proliferation and activation markers of CD8+ T cells was observed, which is consistent with tidutamab’s mechanism of action. The best overall response was stable disease in the analysis to describe clinical activity, and the median duration of treatment was approximately seven months. NETs are an indolent, slow-growing tumor type, and longer follow-up is required to evaluate progression-free survival and the clinical utility of tidutamab for patients with NETs.
A new study for patients with Merkel cell carcinoma and small cell lung cancer, SSTR2-expressing tumor types known to be responsive to immunotherapy, is planned.