A phase I trial targeting advanced or metastatic pancreatic cancer using a combination of standard chemotherapy and adoptively transferred nonengineered, multiantigen specific T cells in the first-line setting (TACTOPS).

4622 Background: Immunotherapy is emerging as a potent therapy for a range of hematologic malignancies and solid tumors. To target pancreatic carcinoma we have developed an autologous, non-engineered T cell therapy using T cell lines that simultaneously target the tumor-associated antigens (TAAs) PRAME, SSX2, MAGEA4, NY-ESO-1 and Survivin. These multiTAA-specific T-cell lines could be consistently prepared by culturing PBMCs in the presence of a Th1-polarizing/pro-proliferative cytokine cocktail, and adding autologous pepmix-loaded DCs as APCs. Methods: Patients with locally advanced or metastatic pancreatic adenocarcinoma who achieved cancer control with three months of standard chemotherapy were eligible to receive up to 6 infusions of multiTAA T-cells (fixed dose - 1x10 7 cells/m 2 ). While also continuing the same chemotherapy, T-cells were given at monthly intervals from month four, onwards. The primary study endpoints were safety and feasibility of completing all 6 planned infusions, with secondary and tertiary endpoints including anti-tumor effects, patient survival, in vivo expansion and T cell persistence of the infused cells as well as recruitment of the endogenous immune system. Results: Between June 2018 and December 2019, we treated 13 patients with multiTAA T-cells. For 12/13 patients, we generated sufficient cells for all 6 planned doses; 2 doses were available for the remaining patient. Of the 13 patients, 8 maintained cancer control for a longer than expected duration, compared to historical controls. With administration of T-cells, 3 of these 8 patients had partial responses and 1 patient had a radiographic complete response (per RECIST). These responses were seen in patients with metastatic cancer. Notably, no patient had infusion-related systemic- or neuro-toxicity. Thus, infusion of autologous multiTAA-targeted T cells directed to PRAME, SSX2, MAGEA4, NY-ESO-1 and Survivin has been safe and provided durable clinical benefit to patients with pancreatic adenocarcinoma. Conclusions: Autologous, TAA cytotoxic T-cells can reliably be generated and safely administered to patients in conjunction with standard of care chemotherapy. In some patients, addition of T-cells may extend duration of first line therapy cancer control and induce additional tumor responses, and activation of the endogenous immune system has been documented in all patients. Exploration in a higher phase study is warranted. Clinical trial information: NCT03192462 .