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

Profile

• AMMF

• CCF (Cholangiocarcinoma Foundation)

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)

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)

Trials and chemotherapy

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

Nakamura Nat Gen 2015

Anatomical specificity

Mutually exclusive or co-existant

Verlingue 2017

IcSe

Massard 2017

MOSCATO

Verlingue 2017

6 responders

6/22 responders out of 1035 patients

assessed were cholangiocarcinoma

Verlingue 2017

IcSe

Cancer is a genetic disease

Cancer is a genetic disease

Cancer is a genetic disease

Cancer is a genetic disease

Cancer is a genetic disease

Median OS 11.7m

RR 40.4%

Hollebeque

ESMO 2018

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

Thanks

All patients, families, investigators and research teams involved

Cancer Research UK Cancer Trials Centre UCL

Funding: