Safety and immunologic impact of neoadjuvant/adjuvant GVAX, cyclophosphamide, pembrolizumab, and anti-CSF1R agent IMC-CS4 in pancreatic adenocarcinoma - PubMed
6 hours ago
- #pancreatic adenocarcinoma
- #CSF1R inhibition
- #immunotherapy
- Previous research linked higher M1/M2 macrophage ratios and fewer PDL1+ M2-like tumor-associated macrophages with improved survival in pancreatic adenocarcinoma (PDA), suggesting targeting M2-like macrophages may enhance outcomes.
- A pilot study tested perioperative combination immunotherapy (GVAX/cyclophosphamide, pembrolizumab, and CSF1 receptor blocker IMC-CS4) in PDA patients, with neoadjuvant and adjuvant phases, followed by maintenance therapy for up to one year.
- Nine patients were treated, with two experiencing immune-related grade 3/4 adverse events (diarrhea and rash), indicating a manageable safety profile.
- Paired biopsy analysis revealed that five of eight evaluable patients met the immunologic endpoint, showing over 80% increase in intratumoral CD8+ T cells, with increases exceeding 1.8 times the baseline median absolute deviation.
- The combination immunotherapy was concluded to be safe and effective in boosting cytotoxic T cells within tumors, supporting further investigation into targeting M2-like macrophages via the CSF1 pathway.