Table 1.
Ongoing ICB-based clinical trials in cholangiocarcinoma.
| Intervention | Trial type | Population (# participants, estimated enrollment) | ClinicalTrials.gov Identifier |
|---|---|---|---|
| Immune checkpoint blockade monotherapy | |||
| Pembrolizumab (anti-PD-1 antibody) | Phase II, single arm, open label; Phase II, non-randomized, open label; Phase Ib, single arm, open label; Phase II, single arm, open label; Prospective observational cohort |
Advanced, refractory BTC (33 pts); Microsatellite unstable cancers, including BTC (171 pts); PD-L1 positive cancers, including BTC (477 pts); Advanced, refractory cancers, including BTC (1,350 pts); HCC or BTC (100 pts) |
NCT03110328; NCT01876511; NCT02054806; NCT02628067; NCT03695952 |
| Nivolumab (anti-PD-1 antibody) | Phase II, single arm, open label; Phase II, non-randomized, open label Prospective observational cohort |
Advanced, refractory BTC (52 pts); Advanced, refractory cancers with MMR deficiency (6,452 pts); HCC or BTC (100 pts) |
NCT02829918; NCT02465060; NCT03695952 |
| Durvalumab (anti-PD-L1 antibody) | Phase I, non-randomized, open label | Advanced solid tumours, including BTC (269 pts) | NCT01938612 |
| Toripalimab (anti-PD-1 antibody) | Phase Ib/II, single arm, open label | HCC or iCCA, eligible for resection (20 pts) | NCT03867370 |
| Atezolizumab (anti-PD-L1 antibody) | Phase II, Non-randomized, open label | Advanced, refractory solid tumours, including BTC, elevated tTMB (765 pts) | NCT02091141 |
| Dual immune checkpoint blockade | |||
| Nivolumab + Ipilimumab (anti-CTLA-4 antibody) | Phase II, single arm, open label; Phase II, randomized, open label |
Advanced, refractory solid tumours including BTC (707 pts); Unresectable, untreated BTC (64 pts) |
NCT02834013; NCT03101566 |
| Durvalumab + Tremelimumab (anti-CTLA-4 antibody) | Phase I, non-randomized, open label | Advanced, refractory, biopsiable solid tumours, including BTC (269 pts) | NCT01938612 |
| Immune checkpoint blockade plus local ablative therapy | |||
| Durvalumab + Tremelimumab + TACE, RFA, or cryoablation | Phase II, non-randomized, open label | Unresectable, refractory HCC or BTC (90 pts) | NCT02821754 |
| Tremelimumab + RFA | Phase I, non-randomized, open label | Unresectable, refractory HCC or BTC, eligible for RFA (61 pts) | NCT01853618 |
| Pembrolizumab + SBRT vs. GEMCIS chemotherapy | Phase II, randomized, open label | Unresectable, untreated iCCA, eligible for radiotherapy (184 pts) | NCT03898895 |
| Durvalumab + Tremelimumab + radiation therapy | Phase II, single arm, open label | Unresectable HCC or BTC (70 pts) | NCT03482102 |
| Immune checkpoint blockade plus chemotherapy | |||
| Durvalumab + Tremelimumab + GEM or GEMCIS vs. GEMCIS chemotherapy | Phase II, randomized, open label | Untreated BTC (63 pts) | NCT03473574 |
| Durvalumab + Tremelimumab + GEMCIS chemotherapy | Phase II, single arm, open label | unresectable, untreated BTC (31 pts) | NCT03046862 |
| Durvalumab + Tremelimumab + Paclitaxel | Phase II, randomized, open label | Recurrent or advanced, refractory BTC (102 pts) | NCT03704480 |
| Durvalumab + GEMCIS vs. GEMCIS chemotherapy | Phase III, randomized, double-blind, placebo-controlled | Unresectable, untreated BTC (474 pts) | NCT03875235 |
| Durvalumab + Guadecitabine | Phase Ib, single arm, open label | Unresectable, refractory HCC, PDAC, or BTC excluding ampullary (90 pts) | NCT03257761 |
| Camrelizumab (anti-PD-1 antibody) + GEMOX chemotherapy | Phase II, single arm, open label | Advanced CCA (38 pts) | NCT03486678 |
| Camrelizumab + Apatinib (VEGFR2 inhibitor), FOLFOX4 or GEMOX chemotherapy | Phase II, non-randomized, open label | Advanced, untreated HCC or BTC (152 pts) | NCT03092895 |
| Pembrolizumab + CAPOX chemotherapy | Phase II, single arm, open label | Unresectable, refractory, biopsiable BTC (19 pts) | NCT03111732 |
| Pembrolizumab + GEMCIS | Phase II, single arm, open label | Unresectable, untreated BTC (50 pts) | NCT03260712 |
| Toripalimab + Gemcitabine | Phase II, single arm, open label | Advanced BTC (40 pts) | NCT03796429 |
| Nivolumab + GEMCIS | Phase I/II, single arm, open label; Phase II, randomized, open label |
Unresectable BTC (30 pts); Unresectable, untreated BTC (64 pts) |
NCT03311789; NCT03101566 |
| nivolumab + nal-irinotecan + 5-fluorouracil + leucovorin | Phase I/II, single arm, open label | Unresectable, refractory BTC (40 pts) | NCT03785873 |
| KN035 (anti-PD-L1 antibody) + GEMOX vs. GEMOX chemotherapy | Phase III, randomized, open label | Unresectable, untreated BTC (390 pts) | NCT03478488 |
| Immune checkpoint blockade plus molecularly targeted therapy | |||
| Pembrolizumab + pemigatinib (FGFR1-3 inhibitor) | Phase I/II, single arm, open label | Advanced, refractory solid tumours, including CCA, with genetic alteration of FGF or FGFR genes (325 pts) | NCT02393248 |
| Nivolumab + FT-2102 (mutant IDH1 inhibitor) | Phase I/II, non-randomized, open label | Selected solid tumours, including BTC, with IDH1 mutations (200 pts) | NCT03684811 |
| Atezolizumab + cobimetinib (MEK inhibitor) | Phase II, randomized, open label | Unresectable, refractory BTC (82 pts) | NCT03201458 |
| Durvalumab + tremelimumab + selumetinib (MEK inhibitor) | Phase I, non-randomized, open label | Advanced, refractory solid tumours, including BTC (58 pts) | NCT02586987 |
| Nivolumab + rucaparib (PARP inhibitor) | Phase II, single arm, open label | Advanced, refractory BTC (35 pts) | NCT03639935 |
| TPST-1120 (PPARα antagonist) + Nivolumab, docetaxel chemotherapy or cetuximab (anti-EGFR antibody) | Phase I, non-randomized, open label | Advanced solid tumours, including CCA (338 pts) | NCT03829436 |
| Pembrolizumab + XL888 (Hsp90 inhibitor) | Phase I, single arm, open label | Advanced, refractory GI cancers, including CCA (50 pts) | NCT03095781 |
| Atezolizumab + DKN-01 (anti-Dickkopf-1 antibody) | Phase I, single arm for BTC, open label | Non-operable, refractory oesophageal and BTC (123 pts) | NCT03818997 |
| Nivolumab, pembrolizumab or chemotherapy + TRK-950 (monoclonal antibody targeting a proprietary tumour antigen) | Phase I, non-randomized, open label | Advanced solid cancers, including CCA (36 pts) | NCT03872947 |
Ongoing clinical trials were identified by searching ClinicalTrials.gov using the terms "Biliary Cancer," "cholangiocarcinoma," "biliary carcinoma," "bile duct," or "biliary tract" and manually curated for inclusion of an immunotherapy arm. Trials were included with status of "Recruiting," "Not yet recruiting," "Active, not recruiting," "Completed," or "Enrolling by invitation." Trials of general solid tumours were excluded unless a BTC arm or inclusion was specified. Search was updated as of 4/1/19. BTC, biliary tract cancer; HCC, hepatocellular carcinoma; iCCA, intrahepatic cholangiocarcinoma; ICB, immune checkpoint blockade; MMR, mismatch repair; PDAC, pancreatic ductal adenocarcinoma; RFA, radio frequency ablation; SBRT, Stereotactic body radiation therapy; TACE, transarterial chemoembolization; TMB, tumor mutational burden.