Safety and immunologic impact of neoadjuvant/adjuvant GM-CSF-secreting allogenic pancreatic tumor cell vaccine (GVAX) combined with cyclophosphamide, pembrolizumab, and macrophage-targeting colony stimulating factor-1 receptor inhibitor IMC-CS4 in pancreatic adenocarcinoma

Background: We previously reported increased M1/M2 ratio and decreased PDL1+ M2-like tumor associated macrophages (TAM) was associated with longer survival in pancreas adenocarcinoma (PDA). We hypothesized targeting M2-like macrophages, regulated by the colony stimulating factor-1 (CSF1) pathway, would be safe and induce an intratumoral immune response. We tested perioperative combination immunotherapy (CI): GVAX/cyclophosphamide (CY), pembrolizumab (Pem), and CSF1 receptor blockade (IMC-CS4) in patients with PDA. Methods: Patients received two neoadjuvant cycles of CI followed by surgery and 4 adjuvant cycles of CI. Subsequently, they received booster Pem every 3 weeks and GVAX/CY every 6 months, for up to one year. Co-primary endpoints were safety and immune response in paired biopsies. Results: Nine patients were enrolled and treated. We observed two immune related grade 3/4 AEs (diarrhea and rash). Comparison of paired biopsies showed 5 of 8 evaluable patients met the immunologic endpoint with >80% increase in CD8+ T cells. The increase was at least 1.8 times the baseline median absolute deviation. Conclusion: CI had a manageable safety profile and led to increased intratumoral cytotoxic effector T cells.