Table 3 Intervention strategy with or without other checkpoint inhibitor
Class | Intervention Strategy | Results | Reference(s) |
|---|---|---|---|
CSF1R | IMC-CS4 (CSF1R mAb) + anti-PD-1 or anti-CTLA-4 | ↑CTL infiltration ↓ Treg infiltration ↑ Antitumor immunity ↓ Tumor growth | |
PLX-3397 (anti-CSF1R) + durvalumab (anti-PD-L1 Ab) | Ongoing Phase I study in advanced pancreatic and colorectal cancers | NCT02777710 | |
JAK/STAT | Ruxolitinib (JAK/STAT inhibitor) | ↓ Tumor growth ↓ PD-L1 expression ↑ CD8+ T cells | [55] |
Ruxolitinib + capecitabine | ↑ survival in metastatic pancreatic cancer who failed to response gemcitabine | [58] | |
BTK | Ibrutinib (BTK inhibitor) | ↓ Infiltration of mast cells ↓ Stromal fibrosis ↓ Tumor progression ↓ IL-2 inducible T-cell kinase | |
Ibrutinib + gemcitabine + nab-paclitaxel | Ongoing Phase I/II study in metastatic pancreatic cancer | NCT02562898 | |
Ibrutinib + gemcitabine + nab-paclitaxel | Ongoing Phase II/III study in metastatic pancreatic cancer | NCT02436668 | |
Radio-therapy (RT) | RT (12 Gy or 5 × 3 Gy) + PD-L1 blocker | ↓ Tumor growth ↓ Treg/MDSC infiltration | |
RT + anti-CTLA-4 mAb / anti-PD-L1 | Ongoing phase Ib in unresctable, non-metastatic pancreatic cancer | NCT02868632 | |
RT + ipilimumab (anti-CTLA-4 mAb) / nivolumab (anti-PD-L1) | Ongoing phase II in metastatic pancreatic cancer | NCT02866383 | |
RT + tremelimumab / MEDI4736 | Ongoing phase I/II in unresectable metastatic pancreatic cancer | NCT02311361 |