Gastroenterology Research and Practice

Review Article

Contemporary Tailored Oncology Treatment of Biliary Tract Cancers

Table 3

On-going clinical trials investigating therapies for advanced biliary tract cancers.


Agent [trial]	Mechanism of action	Population	Phase	Treatment arms	Planned recruitment	Primary endpoint	Clinical trial identifier

Intensified cytotoxic therapies
Nab-paclitaxel	Cytotoxic (antimicrotubule)	2^nd line Unresectable advanced or metastatic biliary tract and gall bladder carcinoma	III Open-label	GEM/CIS+nab-paclitaxel vs. GEM/CIS	Recruiting, target	OS	NCT03768414
mFOLFIRINOX [AMEBICA]	Combination chemotherapy	2^nd line Unresectable advanced or metastatic biliary tract and gall bladder carcinoma	II/III Open-label	mFOLFIRINOX vs. GEM/CIS	Recruiting, target	II: % alive at 6 months without radiological progression III: OS	NCT02591030

Agents targeting FGFR aberrations
Ponatinib	Multitargeted TKI (including FGFR2)	Advanced biliary tract cancer harbouring FGFR2 fusion or amplification, 2^nd line or more	II Single-arm	Ponatinib	Active, not recruiting;	Clinical benefit rate	NCT02265341
Erdafitinib	Pan-FGFR TKI	Advanced solid tumours, including cholangiocarcinoma, with FGFR2 abnormalities	II Single-arm	Erdafitinib	Active, recruiting, target	ORR	NCT02699606
Derazantinib (ARQ087) [FIDES-01]	Multikinase inhibitor	Advanced/inoperable intrahepatic cholangiocarcinoma with FGFR2 fusion, 2^nd line or more	II Single-arm	Derazantinib	Active, recruiting, target	ORR	NCT03230318
TAS-120 [FOENIX101]	Pan-FGFR inhibitor	Advanced solid tumours, including intrahepatic/extrahepatic cholangiocarcinoma, with FGFR2 gene alteration, 2^nd line or more	II Single-arm	TAS-120	Recruiting, target	ORR	NCT02052778
Infigratinib (BJG 398) [PROOF]	FGFR1-3 kinase inhibitor	FGFR2 mutated (fusion/translocations) advanced cholangiocarcinoma, 1^st line	III Open-label	Infigratinib vs. GEM/CIS	Active, recruiting, target	PFS	NCT03773302
Pemigatinib (INCB054828) [FIGHT302]	Pan-FGFR TKI	FGFR2 rearranged advanced/irresectable cholangiocarcinoma	III Open-label	Pemigatinib vs. GEM/CIS	Active, recruiting, target	PFS	NCT03656536

Agents targeting IDH1/IDH2 mutations
BAY1436032	IDH1 inhibitor	IDH-1 mutant advanced solid tumours	I	BAY1436032	Active, not recruiting,	MTD, no. of pts with AEs, established dose for phase II	NCT02746081
Dasatinib	Multitargeted TKI	IDH-1 mutant advanced intrahepatic cholangiocarcinoma	II	Dasatinib	Completed (results awaited),	ORR	NCT02428855
Olaparib	PARP inhibitor	IDH-1/IDH-2 mutant advanced solid tumours	II Single-arm	Olaparib	Recruiting, target	ORR	NCT03212274

Immunotherapy
Pembrolizumab [ABC-09]	Anti-PD1	2^nd line Unresectable or metastatic biliary tract and gall bladder carcinoma	II Single-arm	GEM/CIS+pembrolizumab	Not yet recruiting, target	6-month PFS	NCT03260712
Durvalumab Tremelimumab	Anti-PD-L1 Anti-CTLA4	2^nd line Unresectable or metastatic biliary tract and gall bladder carcinoma	II Single-arm	Durvalumab+tremelimumab+GEM/CIS	Recruiting, target	ORR	NCT03046862
Nivolumab Ipilimumab	Anti-PD1 Anti-CTLA4	2^nd line Unresectable advanced or metastatic biliary tract and gall bladder carcinoma	II Open-label	Nivolumab/ipilimumab vs. GEM/CIS+nivolumab	Recruiting, target	PFS	NCT03101566
Nivolumab	Anti-PD1	2^nd line Unresectable or metastatic biliary tract and gall bladder carcinoma	II Single-arm	Nivolumab	Active, not recruiting,	ORR at 8 weeks	NCT02829918
Pembrolizumab	Anti-PD1	2^nd line or more, advanced irresectable biliary tract cancer	Phase II Single-arm	Pembrolizumab+CAPOX	Recruiting, target	5-month PFS	NCT03111732
Ipilimumab+nivolumab [CHECKMATE848]	Anti-PD1 Anti-CTLA4	Advanced or metastatic TMB-H solid tumours	Phase II Open-label	Ipilimumab+nivolumab vs. nivolumab	Recruiting, target	ORR	NCT03668119
Nivolumab Ipilimumab	Anti-PD1 Anti-CTLA4	Rare tumours (2^nd line or more)	II Single-arm	Nivolumab+ipilimumab	Recruiting, target	Clinical benefit rate	NCT02923934
Nivolumab Ipilimumab [DART]	Anti-PD1 Anti-CTLA4	Advanced GI tumours (2^nd line or more)	II Single-arm	Nivolumab+ipilimumab	Recruiting, target	ORR	NCT02834013
Durvalumab [TOPAZ-1]	Anti-PD-L1	2^nd line Unresectable or metastatic biliary tract and gall bladder carcinoma	III Double-blind	GEM/CIS+durvalumab vs. GEM/CIS+placebo	Recruiting, target	OS	NCT03875235
Autologous tumour-infiltrating lymphocytes+pembrolizmab	TIL Anti-PD1	Metastatic cancer including hepatobiliary (refractory to standard therapy)	II Multiarm	(i) CD enriched TIL (ii) Unselected TIL (iii) Unselected TIL+pembrolizumab prior to cells (iv) Unselected TIL+pembrolizumab at disease progression	Recruiting, target	ORR	NCT01174121
Modified autologous cytokine-induced killer cells	Cytokine-induced killer cells	Cholangiocarcinoma	I/II Single-arm	Cytokine-induced killer cells	Unknown, target	MRI scan for monitoring of tumour size and CIK cell homing	NCT01868490

Agents targeting BRAF mutations
HM95573	RAF inhibitor	Solid tumours with RAS/RAF mutation, 2^nd line or more	I	HM95573	Recruiting, target	ORR	NCT03118817
Vemurafenib+HL-085	BRAF+MAPK inhibition	BRAF V600E mutant advanced solid tumours	I	Vemurafenib+HL-085	Recruiting, target	Incidence of AEs	NCT03781219
Vemurafenib	BRAF inhibitor	Tumours with BRAF mutation, 2^nd line or more	II Single-arm	Vemurafenib	Recruiting, target	ORR	NCT02304809
Encorafenib+MEK162	BRAF inhibitor+MEK inhibitor	BRAF V600E mutant advanced solid tumours	II Single-arm	Encorafenib+MEK162	Recruiting, target	DCR/ORR	NCT01543698
Dabrafenib+trametinib [ROAR]	BRAF inhibitor+MEK inhibitor	Rare tumours with BRAF V600E mutation, 2^nd line or more	II Open-label	Dabrafenib+trametinib	Completed, (BTC, )	ORR	NCT02034110
Binimetinib+encorafenib [BEAVER]	BRAF inhibitor+MEK inhibitor	Advanced solid tumours with BRAF MT (non-V600E), 2^nd line or more	II Single-arm	Binimetinib+encorafenib	Not yet recruiting, target	ORR	NCT03839342

Agents targeting TRK aberrations
Larotrectinib (BAY2757556) [NAVIGATE]	TRK inhibitor	Advanced solid tumours harbouring NTRK fusion, 2^nd line or more	II Single-arm	Larotrectinib	Recruiting, target	ORR	NCT02576431
Entrectinib (RXDX-101) [STARTRK-2]	NTRK1/2/3, ROS1, ALK	Advanced solid tumours that harbour NTRK1/2/3, ROS1, or ALK gene fusion	II Open-label	Entrectinib (RXDX-101)	Recruiting, target	ORR	NCT02568267

Agents targeting BAP1 aberrations
Niraparib [UF-STO-ETI-001]	PARP inhibitor	Advanced solid malignancies with BAP1/DDR defects	II Nonrandomised, open-label	Niraparib	Recruiting, target	ORR	NCT03207347

Agents targeting HER2 aberrations
DS-8201a [HERB]	HER2 inhibitor	HER2-positive biliary tract cancer	II Non-randomised	DS-8201a	Recruiting, target	ORR	JMA-IIA00423

GEM/CIS: gemcitabine+cisplatin; OS: overall survival; mFOLFIRINOX: modified FOLFIRINOX; FGFR: fibroblast growth factor receptor; TKI: tyrosine kinase inhibitor; ORR: overall response rate; PFS: progression-free survival; IDH: isocitrate dehydrogenase; MTD: maximum tolerated dose; AEs: adverse events; PARP: poly(ADP ribose) polymerase; PD1: programmed death 1; PDL1: programmed death ligand 1; CTLA4: cytotoxic T lymphocyte-associated protein 4; TMB-H: tumour mutation burden high; MAPK: mitogen-activated protein kinase; DCR: disease control rate; TRK: tropomyosin receptor kinase; ALK: anaplastic lymphoma kinase; BAP1: BRCA1-associated protein 1; DDR: DNA damage repair; PD: progressive disease.