Table 3.
Completed immunotherapy clinical trials in CCA.
| Monotherapy | ||||
|---|---|---|---|---|
| Target | Agent | Clinical Trial | Response Rate | OS and PFS |
| PD-1, MSI-high, MMR-deficient, or TMB-H | Pembrolizumab | KEYNOTE-028 (NCT02054806), Phase 1b, PDL-1 positive tumors only | ORR: 13.0% (3/23; 95% CI, 2.8–33.6%) | OS: 5.7(95% CI, 3.1–9.8) months; PFS: 1.8 (95% CI, 1.4–3.1) months |
| Nivolumab | NCT02829918 | ORR: 11% | OS: 14.2 (95% CI, 5.98 to not reached) months; PFS 3.68 (95% CI, 2.30–5.69) months | |
| JapicCTI-153098 | ORR: 3% | OS: 5.2 (90% CI, 4.5–8.7) months; PFS 1.4 (90% CI 1.4–1.4) months | ||
| PD-L1 | Durvalumab | NCT01938612 | ORR: 4.8% | OS: 8.1 (95% CI, 5.6–10.1) months; PFS 2 months |
|
Dual
Immunotherapy |
||||
| PD-L1 and CTLA4 | Nivolumab and Ipilimumab | CA209-538 | ORR: 23% | OS: 5.7 months; PFS 2.9 months |
| Durvalumab and Tremelimumab | NCT01938612 | ORR 10.8% | OS: 10.1 months | |
| PD-L1 and TGF-β RII | Bintrafusp alfa | NCT02699514 | ORR: 20% | OS: 12.5 months; PFS 2.5 months |
| NCT03833661 | ORR: 10.1% | PFS 1.8 (95% CI 1.7–1.8) months, OS of 7.6 (95% CI: 4.8–0.5) months. | ||
| PD-1 and | PEG-intron | NCT02982720 | Terminated early | |
| ICI and chemo | ||||
| PD-1 | Nivolumab and gem/cis | JapicCTI-153098 | ORR: 37% | OS: 15.4 months; PFS 4.2 months |
| NCT03311789 | ORR 55.6% | OS: 8.5 months; PFS 6.1 months | ||
| Camrelizumab, gemcitabine/oxaliplatin | NCT03486678 | ORR: 54% | OS: 11.8 months; PFS 6.1 months | |
| Camrelizumab, gemcitabine/oxaliplatin or FOLFOX | NCT03092895 | ORR: 16.3% | OS: 12.4 months; PFS 5.3 months | |
| Toripalimab, gemcitabine/S-1 | NCT03796429 | ORR: 27% | OS: 16 months; PFS 7 months | |
| Pembrolizumab and CAPOX | NCT03111732 | ORR: 27.3% | OS: 6.1 (95% CI 3.1–9.4); PFS: 4.5 (95% CI 2.5 to 9.6) months | |
| PD-L1 | Durvalumab, gem/cis | NCT03046862 | ORR: 73.3% | OS: 18.1 months; PFS 11 months |
| CTLA4 | PEGCISGEM ± Atezolizumab | NCT03267940 | AEs: 100% in both | none (early termination) |
| PD-L1 and CTLA4 | Durvalumab + gem/cis ± tremelimumab | NCT03046862 | ORR: 73.4% | OS: 20.7 months; PFS 11.9 months |
| Other combinations | ||||
| PD-1 and VEGFR2 | Pembrolizumab and Ramucirumab | NCT02443324 | ORR: 4% | OS: 6.4 months; PFS 1.6 months |
| PD-1 and tyrosine kinase | Pembrolizumab/nivolumab and Ramucirumab | NCT03892577 | ORR: 30% | OS: 11 months; PFS 5 months |
| PD-1 and FGFR2 | Pembrolizumab and pemigatinib (dose escalation) | NCT02393248 | - | |
| PD-1 and benzamide histone deacetylase | Nivolimumab and Entinostat | NCT03250273 | ORR: 0% | OS: 6.378 (95% CI 3.748-NR at 36 months) months |
| PD-1 and cell-based | Pembrolizumab and CD8+ T-cells | NCT02757391 | - | |
| PD-L1 | Durvalumab, tremelimumab, radiotherapy |
NCT03482102 | ORR: 25% |