Autologous multiantigen-targeted T cell therapy for pancreatic ductal adenocarcinoma: results of a Phase I, three-arm, nonrandomized clinical trial (TACTOPS)

T-cell therapy has thus far proven ineffective for treating pancreatic ductal adenocarcinoma (PDAC), in part due to heterogeneous expression of tumor-associated antigens (TAAs). In a Phase I/II trial, autologous ex vivo expanded T-cells targeting five TAAs - PRAME, SSX2, MAGEA4, Survivin, and NY-ESO-1 - were prepared and administered (1x107 cells/m2/infusion) monthly to subjects with advanced PDAC responding (Arm A, n=13) or refractory to (Arm B, n=12) first-line chemotherapy, or to those with potentially resectable disease (Arm C, n=12). Primary endpoints were safety and feasibility of delivering 6 infusions; additional endpoints were clinical and immunologic response. Of 56 subjects procured, 37 were infused (median 3 doses), with only one treatment-related serious adverse event reported. Disease control rates in Arms A and B were 84.6% (95% CI: 54.6%-98.1%) and 25% (95% CI: 5.5%-57.2%), respectively; in Arm C, 2/9 resected subjects remain disease-free at 55 and 66 months. The infused cells persisted for up to 12 months post-infusion, and elevated levels of effector, tumor-directed T cells were detected both during dosing (p=0.027) and follow-up in “responders” (objective response in Arms A/B, no relapse in Arm C) compared to “non-responders” (progression in Arms A/B, relapse in Arm C).