Clinical and immunologic assessment of DOC1021 dendritic cell therapy in resectable or borderline resectable pancreatic cancer

Background: Pancreatic ductal adenocarcinoma (PDAC) remains a highly lethal cancer, with 5-year overall survival < 50% even for patients diagnosed early enough to undergo aggressive surgery and chemotherapy. Immunotherapy has shown limited efficacy in PDAC due to heterogeneity of tumor antigens and an immunosuppressive tumor microenvironment. DOC1021 is a cell-based immunotherapy derived from the full complement of autologous tumor antigens. It leverages p38MAPK and mTORC1 signaling cascades to initiate cDC1-like skewing of monocyte-derived DC, generating downstream development of CD8 + tissue-homing, cytolytic memory effectors. Here we report results from a phase I study in which patients with potentially resectable PDAC received DOC1021 after surgical resection and standard neoadjuvant/adjuvant therapy. Methods: To prepare DOC1021, mobilized peripheral blood mononuclear cells (PBMCs) were loaded with autologous tumor lysate and amplified tumor mRNA extracted from resected tumor tissue. After completion of adjuvant therapy, DOC1021 was then administered biweekly via CT-guided injection near lymph nodes in the post-operative surgical bed in conjunction with weekly subcutaneous peg-IFN. Two dose levels (3.5 x 10 6 and 1.4 x 10 7 ) were evaluated. Blood was collected before and ~5 weeks after DOC1021 administration to assess peripheral immune response. Results: Seven patients (median age: 58 years, range: 49-71) received DOC1021 after R0 (71%) or R1 resection (29%) and standard neoadjuvant and/or adjuvant therapy. At the time of analysis, 5 patients are alive (3 of whom remain relapse-free). Three of these patients have achieved post-operative survival exceeding 36 months, while 2 remain under active follow-up with post-operative survival of approximately 16 to 18 months. The most common DOC1021-related adverse events were mild flu-like symptoms, and no dose-limiting toxicities were observed. Post-vaccination, patients exhibited upregulation of CD127 + memory precursor effector cells (MPECs) with additional upregulation of granzyme B and IFN-gamma expression in circulating CD8 + and CD4 + cells, respectively. Conclusions: DOC1021 immunotherapy can be safely delivered after resection of PDAC and standard perioperative therapy with encouraging survival outcomes. Immune profiling revealed increases in MPECs and functional T cell markers, consistent with other DOC1021 studies. A second study arm evaluating vaccination post-surgery but prior to adjuvant therapy is now open and accruing.