Document resource
Background Pancreatic ductal adenocarcinoma (PDAC) is a devastating disease for which 5-year overall survival of early-stage disease is < 50% among patients fit enough to undergo aggressive surgical resection and combination chemotherapy. Immunotherapy for PDAC has shown limited efficacy in part 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 of Group A of a phase I study in which patients with potentially resectable PDAC received DOC1021 after surgical resection and standard neoadjuvant and/or adjuvant therapy.Methods DOC1021 was prepared from mobilized peripheral blood mononuclear cells loaded with autologous tumor lysate and amplified tumor mRNA extracted from tumor tissue harvested at the time of resection. After completion of all standard therapy, vaccine was injected by CT guidance near lymph nodes in the post-operative surgical bed every other week for three doses administered concurrently with 6 weekly subcutaneous doses of peg-IFN. Two dose levels of 3.5 x 10 6 and 1.5 x 107 total vaccine cells were tested.Results Seven patients (median age: 58.0 years, range: 49–71) underwent DOC1021 vaccination after R0 or R1 resection and standard neoadjuvant and/or adjuvant therapy. Five patients received all 3 planned doses whereas 2 patients received only 1 or 2 doses due to peg-IFN attributable cytopenias. A protocol amendment incorporating dose modifications of peg-IFN dosing was subsequently instituted. Vaccines generated for 11 additional subjects were not administered due to progression during adjuvant chemotherapy. The most common DOC1021-related adverse events were mild flu-like symptoms, and no dose-limiting toxicities were observed. At the time of this analysis, 5 patients are alive (3 of whom remain relapse-free), with post-operative survival times of 45, 44, 25, 9.7 and 9.6 months. Gene expression profiling of individual DOC1021 vaccines and peripheral blood T-cell responses are ongoing.Conclusions DOC1021 immunotherapy after surgical resection and standard neoadjuvant and/or adjuvant therapy is safe and feasible in patients with potentially resectable PDAC. An ongoing arm (Group B) is evaluating DOC1021 vaccination after surgery but prior to administration of adjuvant chemotherapy.Acknowledgements This study was supported in part by a grant from Cancer Cures 4 Kids (to WKD) with additional support from Diakonos Oncology Corporation. This study was further supported in part by the Baylor College of Medicine flow cytometry core facility under the academic leadership of Dr. Christine Beeton and the expert assistance of Mr. Joel M. Sederstrom.Ethics Approval This study is being completed under oversight from the WCG institutional review board (reference #20192574), the Baylor College of Medicine institutional review board, an independent data safety monitoring board, and the Food and Drug Administration. All patients provided written, informed consent prior to enrollment.