05 February 2022 : Review article
A Review of Emerging Biomarkers for Immune Checkpoint Inhibitors in Tumors of the Gastrointestinal Tract
Xuqiang Liao1AE, Gao Li1B, Renzhong Cai1AF, Ru Chen1AG*DOI: 10.12659/MSM.935348
Med Sci Monit 2022; 28:e935348
Table 1 Published studies of immune checkpoint inhibitors for gastrointestinal cancers.
| Tumor type | Target/Drug | Trail identifier | Phase | Size | Study design | Clinical efficacy |
|---|---|---|---|---|---|---|
| ESCC []77 | PD-1/Nivolumab | ONO-4538-07 | II | 64 | Single arm | ORR=17% (11/64) |
| ESCC []78 | PD-1/Nivolumab | ATTRACTION-3 | III | 419 | Randomized, open-lable | OS=11.6 months (nivolumab) vs 10.9 (chemotherapy) |
| ESCC []21 | PD-1/Pembrolizumab | KEYNOTE-180 | II | 121 | Single arm | ORR=9.9% (12/121) |
| GC/GEJC []55 | PD-1/Nivolumab | ATTRACTION-2 | III | 493 | Randomized, double-blind | ORR=11.2%(30/268); 1-year OS=26.2% (nivolumab) vs 10.9% (placebo) |
| GC/GEJC []79 | PD-1/Pembrolizumab | KEYNOTE-059 | II | 259 | Single arm | ORR=15.5% (PD-L1+) vs 5.5% (PD-L1−) |
| GC/GEJC []80 | PD-1/Pembrolizumab | KEYNOTE-061 | III | 592 | Randomized, open-label | OS=9.1months (nivolumad) vs 8.3 months (paclitaxel) |
| PD-L1+ GC/GEJC []16 | PD-1/Pembrolizumab | KEYNOTE-012 | Ib | 39 | Single arm | ORR=22% (8/36) |
| dMMR/MSI-H CRC []41 | PD-1/Pembrolizumab | CT01876511 | II | 28 | Single arm | ORR=40% (dMMR/MSI-H) vs 0% (pMMR CRC) |
| dMMR/MSI-H tumors []42 | PD-1/Pembrolizumab | CT01876511 | II | 86 | Single arm | ORR=53%; CR=21% |
| dMMR/MSI-H CRC []45 | PD-1/Nivolumab | Checkmate 142 | II | 74 | Single arm | ORR=31.1% (23/74) |
| dMMR/MSI-H CRC []46 | PD-1+CTLA-4/Nivolumab+ipilimumab | Checkmate 142 | II | 119 | Single arm | ORR=55% (65/119) |
| HCC []20 | PD-1/Nivolumab | Checkmate 040 | I/II | 214 | Dose escalation and expansion | ORR=20% (42/214) |
| HCC []81 | PD-1/Pembrolizumab | KEYNOTE-224 | II | 104 | Non-randomized, open-label | ORR=17% (18/104) |
| HCC []82 | PD-1/Pembrolizumab | KEYNOTE-240 | III | 413 | Randoimzed, double-blind | OS=13.9months (pembrolizumab) vs 10.6 (placebo) |
| PDAC []83 | PD-L1/MDX-1105 | NCT00729664 | I | 207 | Dose escalation | ORR in PDAC=0% (0/14) |
| PDAC []84 | PD-1/Pembrolizumab | NCT02362048 | II | 77 | Randomized, open-label | ORR=7.9%(with pembrolizumab) vs 0% (with acalabrutinib) |
| ESCC – esophageal squamous cell carcinoma; GC or GEJC – gastric or gastroesophageal junction cancer; CRC – colorectal cancer; HCC – hepatocellular carcinoma; PDAC – pancreatic ductal adenocarcinoma; PD-1 – programmed death-1; dMMR – DNA mismatch-repair defect; MSI-H – high microsatellite instability. | ||||||