A phase II study of neoadjuvant GVAX and cyclophosphamide combined with nivolumab and SBRT followed by surgery in borderline resectable pancreatic adenocarcinoma

Abstract Purpose: BR-PDAC is treated with perioperative chemotherapy and surgical resection +/- SBRT, but long-term survival is rare. GVAX is a GM-CSF- secreting vaccine that activates T-cell immunity against tumor-associated antigens. This multi- center phase II clinical trial evaluated the safety and immune effects of GVAX/Cy/nivolumab and SBRT on the PDAC TME. Methods: 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 historical controls treated with neoadjuvant mFOLFIRINOX and SBRT. Pathologic response rate, overall survival, and exploratory immune evaluation of the TME is also reported. Results: 31 patients were enrolled from January 2018 to July 2021. 18 patients received at least one dose of combined immunotherapy. Fourteen patients underwent definitive surgical resection and one complete pathologic complete response was observed. At a median follow-up of 19.5 months, median OS was 20.4 months (95% CI 18.2, NA). There was no difference in the mean CD8 T cell density between study patients as compared to historical control patients. Nonsignificant increases in the abundance score for specific immune cell subsets were observed in responders as compared to non-responders. Conclusions: 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 historical controls. These findings support the need for better characterization of how neoadjuvant immunotherapy may shift the phenotype of the PDAC TME.