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A platform trial of neoadjuvant and adjuvant antitumor vaccination alone or in combination with PD-1 antagonist and CD137 agonist antibodies in patients with resectable pancreatic adenocarcinoma

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机构： [1]The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Department of Oncology, Cancer Convergence Institute and Bloomberg-KimmelInstitute for Cancer Immunotherapy, Johns Hopkins University School of Medicine, Baltimore, MD, USA [2]Vanderbilt University Medical Center, Department ofHematology-Oncology, Nashville, TN, USA [3]The Bloomberg-Kimmel Institute for Cancer Immunotherapy at Johns Hopkins, Baltimore, MD, USA [4]Division ofPancreatic Surgery, Department of General Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan, China [5]Division of Quantitative Sciences,Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, USA [6]The Pancreatic Cancer Precision Medicine Center of ExcellenceProgram at Johns Hopkins, Baltimore, MD, USA [7]Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA [8]Department ofRadiation Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, USA [9]Department of Surgery, Johns Hopkins University School ofMedicine, Baltimore, MD, USA [10]Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA [11]Department of Surgery, New YorkUniversity School of Medicine and NYU-Langone Medical Center, New York, NY, USA

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A neoadjuvant immunotherapy platform clinical trial allows for rapid evaluation of treatment-related changes in tumors and identifying targets to optimize treatment responses. We enrolled patients with resectable pancreatic adenocarcinoma into such a platform trial (NCT02451982) to receive pancreatic cancer GVAX vaccine with low-dose cyclophosphamide alone (Arm A; n = 16), with anti-PD-1 antibody nivolumab (Arm B; n = 14), and with both nivolumab and anti-CD137 agonist antibody urelumab (Arm C; n = 10), respectively. The primary endpoint for Arms A/B - treatment-related change in IL17A expression in vaccine-induced lymphoid aggregates - was previously published. Here, we report the primary endpoint for Arms B/C: treatment-related change in intratumoral CD8+ CD137+ cells and the secondary outcomes including safety, disease-free and overall survivals for all Arms. Treatment with GVAX+nivolumab+urelumab meets the primary endpoint by significantly increasing intratumoral CD8+ CD137+ cells (p = 0.003) compared to GVAX+Nivolumab. All treatments are well-tolerated. Median disease-free and overall survivals, respectively, are 13.90/14.98/33.51 and 23.59/27.01/35.55 months for Arms A/B/C. GVAX+nivolumab+urelumab demonstrates numerically-improved disease-free survival (HR = 0.55, p = 0.242; HR = 0.51, p = 0.173) and overall survival (HR = 0.59, p = 0.377; HR = 0.53, p = 0.279) compared to GVAX and GVAX+nivolumab, respectively, although not statistically significant due to small sample size. Therefore, neoadjuvant and adjuvant GVAX with PD-1 blockade and CD137 agonist antibody therapy is safe, increases intratumoral activated, cytotoxic T cells, and demonstrates a potentially promising efficacy signal in resectable pancreatic adenocarcinoma that warrants further study.© 2023. The Author(s).

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第一作者：

第一作者机构： [1]The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Department of Oncology, Cancer Convergence Institute and Bloomberg-KimmelInstitute for Cancer Immunotherapy, Johns Hopkins University School of Medicine, Baltimore, MD, USA [2]Vanderbilt University Medical Center, Department ofHematology-Oncology, Nashville, TN, USA [3]The Bloomberg-Kimmel Institute for Cancer Immunotherapy at Johns Hopkins, Baltimore, MD, USA

通讯作者：

通讯机构： [1]The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Department of Oncology, Cancer Convergence Institute and Bloomberg-KimmelInstitute for Cancer Immunotherapy, Johns Hopkins University School of Medicine, Baltimore, MD, USA [3]The Bloomberg-Kimmel Institute for Cancer Immunotherapy at Johns Hopkins, Baltimore, MD, USA [6]The Pancreatic Cancer Precision Medicine Center of ExcellenceProgram at Johns Hopkins, Baltimore, MD, USA [8]Department ofRadiation Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, USA

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