A Phase II Study of Neoadjuvant GVAX and Cyclophosphamide Combined with Nivolumab and SBRT Followed by Surgery in Borderline Resectable Pancreatic Adenocarcinoma.

Abstract

Borderline resectable pancreatic ductal adenocarcinoma (PDAC) is treated with perioperative chemotherapy and surgical resection with or without stereotactic body radiotherapy (SBRT), but long-term survival is rare. GVAX is a GM-CSF-secreting vaccine that activates T-cell immunity against tumor-associated antigens. This multicenter phase II clinical trial evaluated the safety and immune effects of GVAX/cyclophosphamide/nivolumab and SBRT on the PDAC tumor microenvironment (TME). Patients received neoadjuvant mFOLFIRINOX or gemcitabine/nab-paclitaxel if intolerant to mFOLFIRINOX followed by combination immunotherapy and SBRT before surgical resection. The primary endpoint was CD8+ T-cell density in surgical specimens compared with in historic control samples treated with neoadjuvant mFOLFIRINOX and SBRT only. Pathologic response rate, overall survival, and exploratory immune evaluation of the TME are also reported. Thirty-one patients were enrolled from January 2018 to July 2021. Eighteen patients received at least one dose of combined immunotherapy. Fourteen patients underwent definitive surgical resection, and one pathologic complete response was observed. At a median follow-up of 19.5 months, the median overall survival was 20.4 months (95% confidence interval, 18.2-not achieved). There was no difference in the mean CD8 T-cell density between study patients and historic control patients. Nonsignificant increases in the abundance score for specific immune cell subsets were observed in responders as compared with nonresponders. The addition of combined immunotherapy and SBRT was safe and feasible in this patient population. No difference was observed in the mean CD8 T-cell density between study patients and historic controls. These findings support the need for better characterization of how neoadjuvant immunotherapy may shift the phenotype of the PDAC TME.