Background• BTC is a rare and aggressive malignancy arising from the biliary

epithelium, characterized by poor prognosis and poor responseto current treatments. The 5-year overall survival rate is 5% to10% for gallbladder cancer and 10% to 40% forcholangiocarcinoma (CCA).

• The incidence of BTC varies widely among different areas of theworld. Generally, the incidence of BTC is lower in Europe andNorth America but higher in Latin America and Asia.

• Like gastric, ovarian, and breast cancer, BTC also involvesmutations in members of the ErbB family. Overexpression ofEGFR, HER2, HER3, and HER4 range from 23-57%, 4-13%, 12-23%, and 59-60% of BTC, respectively.

• Varlitinib is a potent, orally active inhibitor of the receptortyrosine kinases of EGFR, HER2, and HER4 with potent anti-tumor effect in preclinical BTC models.

• Varlitinib also showed tumor shrinkage responses and durabledisease stabilization in BTC patients in phase I studies.

Shukui Qin1, Weijia Fang2, Yuxian Bai3, Xiufeng Liu1, Yifu He4, Jianping Xiong5, Tao Zhang6, Zhendong Chen7, Ying Cheng8, Wei Li9, Jiwei Liu10, Zhiqiang Meng11, Hongming Pan12, Guo-Ping Sun13, Fuxiang Zhou14, Bertil Lindmark15, Hsuan-Jen Shih15, Chih-Yi Hsieh15 ,Nicola McIntyre15, Wei-Ling Chang15

Acknowledgement

Summary

Study Objectives

Study Scheme

References

Study Results

1No.81 Hospital of The Chinese People's Liberation Army, 2The First affiliated hospital of Zhejiang University, 3Harbin Medical University Cancer Hospital, 4Anhui Provincial Cancer Hospital, 5The First Affiliated Hospital of Nanchang University, 6Wuhan Union Hospital, 7The Second affiliated hospital of Anhui Medical University, 8Jilin Province Cancer Hospital, 9The First affiliated hospital of Jilin University, 10The First Affiliated Hospital of Dalian Medical University,

11Fudan University Shanghai Cancer Center, 12Sir Run Run Shaw Hospital, 13The First affiliated hospital of Anhui Medical University, 14Zhongnan Hospital of Wuhan University, 15ASLAN Pharmaceuticals

• This study was sponsored by ASLAN Pharmaceuticals.

JADETREE (Joint Assessment of Drug Efficacy of Pan-Her inhibition using Varlitinib in second line BTC in China ):A phase 2A, single arm, multicentre study of varlitinib plus capecitabine in Chinese patients with advanced or metastatic

biliary tract cancer (BTC).

Major Criteria

About Varlitinib

This study is to assess the efficacy of varlitinib (300 mg twice dailyin a 21-day cycle) plus capecitabine (1,000mg/m2 twice daily for2 weeks followed by a 7-day rest period) in patients withadvanced or metastatic BTC.

Primary Objective:• To assess the efficacy of varlitinib plus capecitabine in patients

with advanced or metastatic biliary tract cancer whoprogressed on first line of systemic therapy as measured byObjective Response Rate (ORR) based on RECIST v1.1.

Secondary Objectives:• To evaluate the efficacy of varlitinib plus capecitabine, as

measured by duration of confirmed response (DoR),progression-free survival (PFS), overall survival (OS) and diseasecontrol rate (DCR)

• To assess the safety and tolerability of varlitinib whencombined with capecitabine

A phase 2A, single arm, multicentre study of varlitinib pluscapecitabine in Chinese patients with advanced or metastaticbiliary tract cancer who progressed on at least 1 line of systemictherapy.

� Key inclusion criteria include having failed gemcitabine-containing 1st linesystemic treatment, and no evidence of biliary duct obstruction (unless controlledby local treatment or endoscopic or percutaneous decompression).

� Treatment will continue until disease progression or unacceptable toxicity,withdrawal of consent, or death

• Screening period: 3 weeks• Treatmento Varlitinib 300 mg BID every day+ Capecitabine 1000 mg/m2

BID for 2 weeks followed by a 1-week rest until diseaseprogression, unacceptable toxicity, consent withdrawal ordeath

o Radiological imaging to assess disease status will beperformed at baseline and every 6 weeks until diseaseprogression to evaluate the efficacy of treatment accordingto RECIST Version 1.1

• Safety follow up: 28 days after the last dose of studymedication

Study Design (continued)

• Have histologically or cytologically confirmed advanced(unresectable) or metastatic BTC, including intrahepatic orextrahepatic CCA, gallbladder cancer and carcinoma of Ampullaof Vater. This includes clinical diagnosis of BTC with histologicalconfirmation of adenocarcinoma.

• Have received and failed one and only one prior line of systemictreatment for advanced or metastatic disease with radiologicevidence of disease progression. This prior line of systemictreatment must also contain gemcitabine.

• Have not been previously treated with varlitinib or capecitabineas first line therapy for advanced or metastatic disease. Forpatients who have previously received capecitabine asradiosensitizer or as part of their adjuvant therapy and theirdisease has relapsed for more than 6 months after their lastdose of capecitabine adjuvant therapy, their capecitabinetherapy will not be considered as a line of systemicchemotherapy for metastatic/advanced disease, and thus theycan participate in the study.

• Have radiographically measurable disease based on ResponseEvaluation Criteria in Solid Tumors (RECIST) v1.1.

• Have no evidence of biliary duct obstruction, unless obstructionis controlled by local treatment or, in whom the biliary tree canbe decompressed by endoscopic or percutaneous stenting withsubsequent reduction in bilirubin to below or equal to 1.5 ×upper level of normal.

• Have no known metastatic brain lesion(s), includingasymptomatic and well controlled lesion(s).

Baseline Characteristic

The enrollment started in December, 2017. As of 3rd September2018, 46 patient has been screened and 33 patients wereenrolled while 3 patients are in screening.

• This study is to assess the efficacy of varlitinib plus capecitabinein patients with advanced or metastatic BTC.

• Current varlitinib/capecitabine is safe and tolerated without anyunexpected adverse event.

• The study is ongoing and approximately 68 patients will berecruited in the study.

Other Information• Clinical trial identification: ClinicalTrials.gov NCT03231176.

Contact information:• qinsk@csco.org.cn• samuel.shih@aslanpharma.com• Chih-Yi.Hsieh@aslanpharma.com

1. Ghosn M, Kourie HR, El Rassy E, eEt al. Optimum chemotherapy forthemanagement of advanced biliary tract cancer. World J Gastroenterol. 2015Apr14;21(14):4121-5.

2. Mitsunaga S, Kojima M, Ikeda M, Ochiai. Et al. Membranous expressions ofErbB family in biliary tract cancer [Abstract]. The 76th Annual Meeting of theJapanese Cancer Association, Japan

3. Yang X, Wang W, Wang C, et al. Characterization of EGFR family geneaberrations in cholangiocarcinoma. Oncol Rep. 2014;32(2):700-8

4. Pignochino Y, Sarotto I, Peraldo-Neia C, et al. Targeting EGFR/HER2 pathwaysenhances the antiproliferative effect of gemcitabine in biliary tract andgallbladder carcinomas. BMC Cancer. 2010;10:631.

5. Yoshikawa D, Ojima H, Iwasaki M, et al. Clinicopathological and prognosticsignificance of EGFR, VEGF, and HER2 expression in cholangiocarcinoma. Br JCancer. 2008;98(2):418-25.

6. Zhang Z, Oyesanya RA, Campbell DJ, et al. Preclinical assessment ofsimultaneous targeting of epidermal growth factor receptor (ErbB1) and ErbB2as a strategy for cholangiocarcinoma therapy. Hepatology. 2010 ;52(3):975-86.

Statistical AnalysisThe study has not been formally powered for hypothesis testing,however, it has been designed to provide a clear distinctionbetween historical response rates of 6-8% ORR in similarpopulations treated with capecitabine monotherapy with a 95%confidence interval.

Copies of this poster obtained throughQuick Response (QR) Code are forpersonal use only and may not bereproduced without permission fromASLAN Pharmaceuticals and the authorof this poster

Study duration is divided in three different stages:

Screening / Baseline

• Up to 3 weeks

Treatment Period

• 3 weeks cycle until disease progression

Safety Follow Up

• 28 days after last dose of study medication

Study Design

Subject by Age

3

14

11

5

0

2

4

6

8

10

12

14

16

41-50 51-60 61-70 71-80

# Su

bjec

t

Age

% Subject by Gender

* Median age: 59 (43-77)

ECOG at C1D1

0

5

10

15

20

ECOG 0 ECOG 1

Primary Tumor Site

N=14

N=19

Intrahepatic bile ductn=16 (48%)

Extrahepatic bile ductn=4 (12%)

Ampulla of Vater,n=2 (6%)

Gallbladdern=11 (33%)

Malen=16 (48%) Female

n=17 (52%)