Neoadjuvant and adjuvant vaccine therapy with or without PD1 checkpoint inhibitor therapy in patients with resectable pancreatic cancer: a trial in progress

Abstract

Objective: Our group has developed an irradiated GM-CSF secreting allogenic pancreatic adenocarcinoma (PDA) vaccine (GVAX). Multiple trials have shown GVAX to be safe with a survival benefit associated with enhancement of intratumoral antigen specific T-cells. The PDA microenvironment inhibits the most effective immune response. Our preclinical model suggests GVAX primes the PDA microenvironment for PD-1 checkpoint inhibitor therapy (nviolumab), and in combination vaccine-induced anti-tumor T-cell responses may be enhanced. Methods: 50 patients with resectable PDA will be enrolled and randomized to receive neoadjuvant treatment with GVAX plus cyclophosphamide (Cy/GVAX) or Cy/GVAX combined with nivolumab. All subjects will receive 5 additional adjuvant immunotherapy treatments. A core-needle biopsy obtained prior to first treatment, along with the surgical specimen will be used for evaluation of IL17A expression in vaccine-induced lymphoid aggregates. Safety, disease free survival (DFS) and overall survival (OS) will be assessed. PD1 pathways and vaccine-induced immune regulatory signatures in the microenvironment will be evaluated through immunohistochemistry and mRNA sequencing. Results: Accrual has initiated and enrolled 6 subjects. All 6 have received neoadjuvant immunotherapy and undergone pancreatectomy, with 5 receiving the second adjuvant immunotherapy treatments. Tumor infiltrating immune cells have been collected with initiation of preliminary staining of CD3, CD4, CD8, CD65 and FOXP3. Conclusion: We will continue patient enrollment and analysis of immune parameters. Surgical outcomes, DFS and OS will be assessed as the study matures. Altering the immune environment with combination immunotherapy is a novel approach for the treatment of patients with PDA and other non-immunogenic cancers.