Treatment Options for Advanced Cholangiocarcinoma

Farshid Dayyani, MD, PhD | FRIDAY, FEB. 28th 2020

Epidemiology • 3 Subtypes: • intrahepatic, perihilar, and distal

• Incidence 1.2/100,000 per year in U.S.

• 3% of GI cancers , but accounts for 20% of deaths from hepatobiliary cancers (median OS about one year)

• Rising incidence from 2001 – 2015• NASH, Hep C, Cirrhosis

• Only curative option is resection, but 2/3 diagnosed at advanced stage

Gemcitabine/Cisplatin in 1L advanced Cholangiocarcinoma: ABC-02 Trial

PR= 45%, DCR 84%

PFS= 11.8 mo

OS= 19.2 mo

ABC-06: second–line mFOLFOX vs active symptom control

Presented By Jennifer Knox at 2020 Gastrointestinal Cancer Symposium

Molecular characterization of cholangiocarcinoma

Presented By Jennifer Knox at 2020 Gastrointestinal Cancer Symposium

Targeted Therapy for Biliary Tract Cancers

Presented By William Harris at 2019 ASCO Annual Meeting

The IDH family of enzymes:

cytoplasm and peroxysomes (IDH1) mitochondria (IDH2 and IDH3) involved in a number of cellular processes

• mitochondrial oxidative phosphorylation

• glutamine metabolism• Lipogenesis• glucose sensing• regulation of cellular redox status

Targeting IDH1 population (ClarIDHy)

Presented By Jennifer Knox at 2020 Gastrointestinal Cancer Symposium

ClarIDHy Trial: Overall Survival

1. Abou-Alfa et al. Presented at: 2019 ESMO Congress; September 27 to October 1, 2019; Barcelona, Spain. Abstract LBA10_PR. 2. Faivre et al Ann Oncol 2017. 3. Yao et al J Clin Oncol 2016

FIGHT-202: a phase 2 study of pemigatinib in patients with previously treated locally advanced or metastatic CCA

Annals of Oncology (2019) 30 (suppl_5): v851-v934. 10.1093/annonc/mdz3

FIGHT-202: Response and Survival Cohort A

Targeted Therapy in Molecularly-Altered Advanced Cholangiocarcinoma

Ivosidenib1 Infigratinib2 Pemigatinib3 Dabrafenib + Tremetinib4

N 124 71 107 35

Target IDH FGFR FGFR BRAF

ORR 2% 25.4% 35.5% 36%

DCR 53% 83.6% 82% 75%

mPFS 2.7 months 6.8 months 6.9 months 9.2 months

mOS 10.8 months 12.5 months 21.1 months 11.7 months

Figure Adapted From:1Abou-Alfa et al ESMO 2019; 2 Javle et al ESMO 2018 3Vogel et al ESMO 2019; 4Wainberg et al ASCO GI 2019

Other promising targets not to overlook in BTC

Presented By Jennifer Knox at 2020 Gastrointestinal Cancer Symposium

Locoregional Treatment in Advanced IHC

Locoregional Treatment in Advanced IHC

Clinical Trial Currently Enrolling at UC Irvine:1. UCI 19-20 - A Phase III Randomized, Double-Blind, Placebo-Controlled, Multi-

Regional, International Study of Durvalumab in Combination with Gemcitabine Plus Cisplatin Versus Placebo in Combination with Gemcitabine Plus Cisplatin for Patients With First-Line Advanced Biliary Tract Cancers (TOPAZ-1)

2. SWOG-S1815 - A Phase III Randomized Trial of Gemcitabine, Cisplatin, and Nab-Paclitaxel Versus Gemcitabine and Cisplatin in Newly Diagnosed, Advanced Biliary Tract Cancers

3. UCI 18-104 - A Phase III, Open-Label, Randomized, Active-Controlled, Multicenter Study to Evaluate the Efficacy and Safety of INCB054828 versus Gemcitabine Plus Cisplatin Chemotherapy in First-Line Treatment of Participants with Unresectable or Metastatic Cholangiocarcinoma with FGFR2 Rearrangement

An Approach to Personalised Medicine in Advanced BTC Today/Tomorrow

Presented By Jennifer Knox at 2020 Gastrointestinal Cancer Symposium

Thank You

fdayyani@hs.uci.edu

Treatment Options for Advanced CholangiocarcinomaEpidemiologyGemcitabine/Cisplatin in 1L advanced Cholangiocarcinoma: ABC-02 TrialSlide Number 4Slide Number 5ABC-06: second–line mFOLFOX vs active symptom controlMolecular characterization of cholangiocarcinomaTargeted Therapy for Biliary Tract CancersSlide Number 9Targeting IDH1 population (ClarIDHy)ClarIDHy Trial: Overall Survival�Slide Number 12FIGHT-202: a phase 2 study of pemigatinib in patients with previously treated locally advanced or metastatic CCAFIGHT-202: Response and Survival Cohort ATargeted Therapy in Molecularly-Altered Advanced Cholangiocarcinoma Other promising targets not to overlook in BTCLocoregional Treatment in Advanced IHCLocoregional Treatment in Advanced IHCClinical Trial Currently Enrolling at UC Irvine:An Approach to Personalised Medicine in Advanced BTC Today/TomorrowThank You��fdayyani@hs.uci.edu