TABLE 1.
Selected ongoing clinical trials with immunotherapy in BTC
| Therapeutic | Target | Phase | Status | Design | Trail NCT | Endpoints |
|---|---|---|---|---|---|---|
| (a) Checkpoint inhibitor monotherapy | ||||||
| Pembrolizumab (MK‐3475) | PD‐1 | Ib | Active, not recruiting | Single Group Assignment | NCT02054806 | ORR/PFS |
| Pembrolizumab (MK‐3475) | PD‐1 | II | Recruiting | Single Group Assignment | ORR/PFS; ORR | |
| Nivolumab | PD‐1 | II | Active, not recruiting | Single Group Assignment | NCT02829918 | ORR |
| STI‐3031 | PD‐L1 | II | Not yet recruiting | Single Group Assignment | NCT03999658 | ORR/DOR/PFS |
| M7824 | PD‐L1 | II | Recruiting | Single Group Assignment | NCT03833661 | OR/DOR |
| Nivolumab or pembrolizumab | PD‐1 | ‐ | Recruiting | Prospective Cohort Study | NCT03695952 | ORR |
| (b) Dual checkpoint inhibition | ||||||
|
MEDI4736 Tremelimumab |
PD‐L1 monotherapy/with CTLA‐4 | I | Active, not recruiting | Parallel Assignment | NCT01938612 | Safety and tolerability |
|
Nivolumab Ipilimumab |
PD‐1 CTLA‐4 |
II | Recruiting | Parallel Assignment | NCT02834013 | ORR |
| Gemcitabine + Cisplatin + Nivolumab; Nivolumab + Ipilimumab |
PD‐1 PD‐1+ CTLA‐4 |
II | Active, not recruiting | Parallel Assignment (Randomized) | NCT03101566 | PFS |
| (c) Checkpoint inhibition plus myeloid cell immunosuppression | ||||||
|
Pembrolizumab Sargramostim |
PD‐1 GM‐CSF |
II | Active, not recruiting | Single Group Assignment | NCT02703714 | ORR |
|
Nivolumab Nivolumab + Cabrilizumab |
PD‐1 CSF‐1R |
‐ | Recruiting | Parallel Assignment (Randomized) | NCT03768531 | Safety and tolerability |
| (d) Adoptive cell therapy | ||||||
|
IL‐2 HER2Bi‐Armed T Cells |
I | Unknown | Single Group Assignment | NCT02662348 | Safety and tolerability | |
| CART‐HER‐2 | I | Unknown | Single Group Assignment | NCT01935843 | Safety and tolerability | |
| CART‐EGFR | I | Unknown | Single Group Assignment | NCT01869166 | Safety and tolerability | |
| Cytokine induced killer cells | I | Recruiting | Single Group Assignment | NCT01868490 | Tumor size and CIK cell–homing | |
|
TC‐210 T Cells TC‐210 + fludarabine + cyclophosphamide TC‐210+ fludarabine + cyclophosphamide + anti‐PD1 |
I/II | Recruiting | Single Group Assignment | NCT03907852 | Safety and tolerability | |
| Tumor‐Infiltrating Lymphocytes (TIL) | II | Recruiting | Single Group Assignment | NCT03801083 | ORR/CRR/DOR | |
| MUC‐1 CART cell | ‐ | Recruiting | Single Group Assignment | NCT03633773 | DCR/ORR | |
| (e) Adoptive cell therapy plus checkpoint inhibition | ||||||
|
CD8+ T Cell Aldesleukin Cyclophosphamide Pembrolizumab |
I | Active, not recruiting | Single Group Assignment | NCT02757391 | Safety and tolerability | |
|
'SMT‐NK' Inj Pembrolizumab |
I/IIa | Recruiting | Single Group Assignment | NCT03937895 |
Phase I: RP2D Phase IIa: ORR |
|
| (f) Checkpoint inhibition plus targeting | ||||||
|
Ramucirumab Pembrolizumab |
VEGFR‐2 PD‐1 |
I | Active, not recruiting | Parallel Assignment | NCT02443324 | Number of participants who experienced DLTs |
|
Guadecitabine Durvalumab |
DNMT PD‐L1 |
Ib | Recruiting | Single Group Assignment | NCT03257761 | Incidence of TEAEs, RP2D |
|
Anlotinib TQB245 |
VEGFR, PDGFR, FGFR, c‐Kit PD‐L1 |
Ib | Recruiting | Single Group Assignment | NCT03996408 | DLT/MTD/RP2D/ORR |
|
Regorafenib Avelumab |
VEGFR1‐3, PDGFR‐β, Kit, RET, Raf‐1 PD‐L1 |
I/II | Recruiting | Sequential Assignment | NCT03475953 |
Phase I: RP2D Phase II: ORR |
|
FT‐2102 Nivolumab |
IDH1 PD‐1 |
Ib/II | Recruiting | Parallel Assignment | NCT03684811 |
Phase Ib: DLT/RP2D Phase II: ORR |
|
Lenvatinib Pembrolizumab |
VEGFR1‐3, FGFR1‐4, PDGFR‐β, RET, KIT PD‐1 |
II | Recruiting | Single Group Assignment | NCT03895970 | ORR/DCR/PFS |
|
Lenvatinib Pembrolizumab |
VEGFR1‐3, FGFR1‐4, PDGFR‐β, RET, KIT PD‐1 |
II | Active, not recruiting | Single Group Assignment | NCT03797326 | ORR, Incidence of TEAEs |
|
Rucaparib Nivolumab |
PARP PD‐1 |
II | Recruiting | Single Group Assignment | NCT03639935 | PFS |
|
Axitinib Toripalimab |
VEGFR1‐3, PDGFR‐β, c‐Kit PD‐1 |
II | Not yet recruiting | Single Group Assignment | NCT04010071 | ORR/PFS |
|
Olaparib Durvalumab |
PARP PD‐L1 |
II | Not yet recruiting | Parallel Assignment | NCT03991832 | ORR/DCR |
|
DKN‐01 Nivolumab |
DKK1 PD‐1 |
II | Recruiting | Parallel Assignment | NCT04057365 | ORR |
|
SHR‐1210 + Apatinib SHR‐1210 + FOLFOX4/GEMOX regimen |
PD‐1, VEGFR‐2 PD‐1+ chemotherapy |
II | Recruiting | Parallel Assignment | NCT03092895 | Safety and tolerability |
|
Entinostat Nivolumab |
HDAC1, HDAC3 PD‐1 |
II | Recruiting | Parallel Assignment | NCT03250273 | ORR |
|
Atezolizumab Atezolizumab + Cobimetinib |
PD‐L1 MEK |
II | Active, not recruiting | Parallel Assignment (Randomized) | NCT03201458 | PFS |
| (g) Checkpoint inhibition plus chemotherapy | ||||||
|
Nivolumab Gemcitabine Cisplatin |
PD‐1 | I/II | Unknown | Single Group Assignment | NCT03311789 | 6‐month PFS rate, mOS |
|
INT230‐6 Pembrolizumab or anti‐CTLA‐4 antibody |
PD‐L1 CTLA‐4 |
I/II | Recruiting | Sequential Assignment | NCT03058289 | Safety and tolerability |
|
Manganese chloride Nab‐paclitaxel Gemcitabine Anti‐PD‐1 antibody |
PD‐1 | I/II | Recruiting | Single Group Assignment | NCT04004234 | Incidence of TEAEs, PFS |
|
Nivolumab Nanoliposomal‐Irinotecan 5‐Fluorouracil Leucovorin |
PD‐1 | Ib/II | Recruiting | Single Group Assignment | NCT03785873 |
Phase Ib: Incidence of DLTs Phase II: mPFS |
|
Nivolumab TS‐1 Gemcitabine |
PD‐1 | II | Recruiting | Single Group Assignment | NCT04172402 | ORR |
|
Toripalimab Gemcitabine 5‐ fluorine pyrimidine |
PD‐1 | II | Recruiting | Single Group Assignment | NCT03982680 | 6‐month PFS rate, mPFS, toxic side effects |
|
Toripalimab S1 Albumin Paclitaxel |
PD‐1 | II | Recruiting | Single Group Assignment | NCT04027764 | ORR/PFS/DCR/OS |
|
SHR‐1210 GEMOX |
PD‐1 | II | Recruiting | Single Group Assignment | NCT03486678 | 6‐month PFS rate, incidence of TEAEs |
|
Pembrolizumab Oxaliplatin Capecitabine |
PD‐1 | II | Recruiting | Single Group Assignment | NCT03111732 | 5‐month PFS rate, safety, ORR, OS |
|
Pembrolizumab Cisplatin Gemcitabine |
PD‐1 | II | Recruiting | Single Group Assignment | NCT03260712 | 6‐month PFS rate, ORR, toxicity |
|
GS Toripalimab |
PD‐1 | II | Recruiting | Single Group Assignment | NCT03796429 | PFS/OS/ORR |
|
Durvalumab Tremelimumab Gemcitabine/ Cisplatin |
PD‐L1 CTLA‐4 |
II | Recruiting | Single Group Assignment | NCT03046862 | ORR/DCR/PFS/OS |
|
Durvalumab + Tremelimumab + Gemcitabine Durvalumab + Tremelimumab + Gemcitabine + Cisplatin Gemcitabine + Cisplatin |
PD‐L1 CTLA‐4 |
II | Recruiting | Parallel Assignment (Randomized) | NCT03473574 | ORR, OS, incidence of TEAEs |
|
M7824 + Gemcitabine + Cisplatin Placebo + Gemcitabine + Cisplatin |
PD‐L1 | II/III | Recruiting | Parallel Assignment (Randomized) | NCT04066491 | Number of participants who experienced DLTs, OS |
|
Pembrolizumab + Gemcitabine + Cisplatin Placebo + Gemcitabine + Cisplatin |
PD‐1 | III | Recruiting | Parallel Assignment (Randomized) | NCT04003636 | PFS/OS/ORR |
|
Durvalumab + Gemcitabine + Cisplatin Placebo + Gemcitabine + Cisplatin |
PD‐L1 | III | Recruiting | Parallel Assignment (Randomized) | NCT03875235 | OS/PFS/ORR |
|
KN035 + Gemcitabine + oxaliplatin Gemcitabine + oxaliplatin |
PD‐L1 | III | Recruiting | Parallel Assignment (Randomized) | NCT03478488 | OS/PFS/ORR |
| (h) Checkpoint inhibition plus targeting and chemotherapy | ||||||
|
Oxaliplatin Gemcitabine Lenvatinib JS001 |
VEGFR1‐3, FGFR1‐4, PDGFRα, RET, KIT PD‐1 |
II | Active, not recruiting | Single Group Assignment | NCT03951597 | ORR/OS/PFS |
| (i) Checkpoint inhibition plus ablative local therapy | ||||||
|
Tremelimumab Durvalumab Radiation |
CTLA‐4 PD‐L1 |
II | Recruiting | Single Group Assignment | NCT03482102 | ORR, incidence of TEAEs, OS, DCR, PFS |
|
Durvalumab + Tremelimumab Durvalumab + Tremelimumab + TACE Durvalumab + Tremelimumab + RFA Durvalumab + Tremelimumab + Cryoablation |
PD‐L1 CTLA‐4 |
II | Recruiting | Parallel Assignment | NCT02821754 | PFS, incidence of TEAEs |
|
Radiotherapy + Camrelizumab Gemcitabine + Cisplatin |
PD‐1 | II | Recruiting | Parallel Assignment (Randomized) | NCT03898895 | PFS, OS, incidence of TEAEs |
|
Nivolumab + RA Nivolumab + Ipilimumab + RA |
PD‐1 CTLA‐4 |
II | Recruiting | Parallel Assignment (Randomized) | NCT02866383 | CBR, incidence of TEAEs, ORR, PFS, OS |
Abbreviations: CTLA‐4, cytotoxic T lymphocyte–associated protein 4; DCR, disease control rate; DLT, dose‐limiting toxicity; DOR, duration of response; GM‐CSF, human granulocyte‐macrophage colony‐stimulating factor; HDAC, histone deacetylases; MEK, methyl ethyl ketone; mOS, median OS; mPFS, median PFS; ORR, objective response rate; OS, overall survival; PDGFR‐β, platelet‐derived growth factor receptor beta; PD‐1, programmed cell death protein 1; PD‐L1, programmed cell death 1 ligand 1; PFS, progression‐free survival; RP2D, recommended phase 2 dose; NCT, national clinical trial; MTD, maximum tolerated dose; CIK, cytokine‐induced killer; TEAE, treatment emergent adverse event; CBR clinical benefit rate.