ammf 9 may 2019
TRANSCRIPT
Cholangiocarcinoma
treatments and trials
John BridgewaterUCL Cancer Institute, London
AMMF
9th May 2019
What’s happened in cholangiocarcinoma
treatment?
• Profile
• Chemotherapy
• Biological and other therapies
• What’s next?
Profile
• AMMF
• CCF (Cholangiocarcinoma Foundation)
• ENS-CCA (European network for the study of
Cholangiocarcinoma)
Profile
• AMMF
• CCF (Cholangiocarcinoma Foundation)
• ENSCCA (European network for the study of
Cholangiocarcinoma)
• CCA UK
Profile
• AMMF
• CCF (Cholangiocarcinoma Foundation)
• ENSCCA (European network for the study of
Cholangiocarcinoma)
• CCA UK
• IBTCC (International Biliary Tract Cancer
Collaborators)
Profile
• AMMF
• CCF (Cholangiocarcinoma Foundation)
• ENSCCA (European network for the study of
Cholangiocarcinoma)
• CCA UK
• IBTCC (International Biliary Tract Cancer
Collaborators)
• EURACAN
Obstacles to evaluation of treatments
• Uncommon cancers
(1500/UK/PA or
50/network)
– Small studies
– Prolonged (and failed)
accrual
– Studies statistically
underpowered
– Heterogeneous
populations
– (Limited pharma
interest)
• Disease group
– Unwell (sepsis and
biliary obstruction)
– Elderly
• Histological/cytological
confirmation difficult
• Disease often not
measurable (unreliable
response assessment)
Study description Treatment Study size Outcome Date
Advanced disease
ABC-01 Randomised phase
2
Gem vs CisGem 86 Published 2001-4
ABC-02 Phase 3 Gem vs CisGem 410 Published 2004-9
ABC-03 Randomised phase
2
CisGem +/-cedirinib 126 Published 2011-2
ABC-04 Phase 1b CisGem +
Selumetinib
13 Published 2012-3
ABC-06 Phase 3 FOLFOX vs
surveillance
170 ASCO 19 2013-6
ABC-07 Phase 2 CisGem+/-SBRT 76 Accruing 2013-
ABC-08 Phase 1b CisAcelarin 24 Completed 2016-8
ABC-09 Phase 2 CisGemPembro 50 In set-up
Adjuvant
BILCAP Phase 3 Cape vs
surveillance
447 Published 2005-14
ACTICCA-01 Phase 3 CisGem vs cape 768 Accruing 2013-
Photodynamic
Therapy
Photostent-02 Phase 3 PDT vs surveillance 98 Published 2004-9
Neoadjuvant
BBC-01 Phase 2 CisGem 12-24 In set-up 2019
Study description Treatment Study size Outcome Date
Advanced disease
ABC-01 Randomised phase
2
Gem vs CisGem 86 Published 2001-4
ABC-02 Phase 3 Gem vs CisGem 410 Published 2004-9
ABC-03 Randomised phase
2
CisGem +/-cedirinib 126 Published 2011-2
ABC-04 Phase 1b CisGem +
Selumetinib
13 Published 2012-3
ABC-06 Phase 3 FOLFOX vs
surveillance
170 ASCO 19 2013-6
ABC-07 Phase 2 CisGem+/-SBRT 76 Accruing 2013-
ABC-08 Phase 1b CisAcelarin 24 Completed 2016-8
ABC-09 Phase 2 CisGemPembro 50 In set-up
Adjuvant
BILCAP Phase 3 Cape vs
surveillance
447 Published 2005-14
ACTICCA-01 Phase 3 CisGem vs cape 768 Accruing 2013-
Photodynamic
Therapy
Photostent-02 Phase 3 PDT vs surveillance 98 Published 2004-9
Neoadjuvant
BBC-01 Phase 2 CisGem 12-24 In set-up 2019
Standard
of care
International Cancer Genome ConsortiumICGC Cancer Genome Projects
- Somatic mutations- Copy number variation- Structural Variation- Mutation Signature- Methylation- Integration or presence of pathogen genome- Non-coding DNA changes
ICGC Biliary Tract Cancer Program
Mostly post-operative
Intrahepatic
Fluke vs non-fluke
FOUNDATIONONE
TESTING(TISSUE OR LIQUID BIOPSY)
3 months Cis-Gem1
Disease control
N=476, targetable
N=240
SAFIR-ABC10 Screening
Study N= 800
Targeted N=160 SoC N=80
SoC Targeted
FGFR studies
Pharma vs Drug Platform
Incyte CisGem 1st Pemigatinib FM
TAIHO CisGem 1st
Mono 2nd
TAS120 Any
QED CisGem 1st Infigratinib
(BJG398)
FISH
Basilea Maintenance
vs placebo
Tivantinib
(ARQ197)
FISH
Debiopharm 2nd Debio1347
Janssen 2nd Erdafitinib
Others…
• FT-2102 (IDH1)
• Regorafenib
• EDO S7.1
• M7824
• KA2507
• CisGem +/- IO (pembrolizumab, durvulumab)
• CisAcelarin vs CisGem
70 years BRAF G469A mutation iCC D Sept 17
Post-resection, adjuvant capecitabine (PD) and CisGem (PD)
Cetuximab, Encorafenib and Binimetinib (as in BEACON)
8 weeks CEB
G1 rash, diarrheoa and fatigue
PS1
Treatment continuing as of 3-5-19 (>6m)
Summary
• SoC established
• Cholangiocarcinoma may be promising for
targeted therapy
• Genomic testing critical
• Providers need to adapt: pharma and NICE