Study of Vismodegib in Advanced Gastric Adenocarcinoma Patients With SMO Overexpression

Inclusion Criteria:

1. Provision of fully informed consent prior to any study specific procedures.
2. Patients must be ≥20 years of age.
3. Advanced gastric adenocarcinoma (including GEJ) that has progressed during or after 1st line or second-line therapy.

• Both fluoropyrimidine and platinum agent need to be contained in the priorchemotherapies
• Prior adjuvant or neoadjuvant therapy is counted as 1 regimen, provided thatdisease progression occurs within 6 months after the completion of adjuvant orneoadjuvant therapy.
• Acceptable prior chemotherapy regimens for this protocol are chemotherapyregimens that include Immune Target agent therapy. (such as a pembrolizumab,ramucirumab etc)

4. Have the presence of measurable disease as defined by the Response Evaluation Criteriain Solid Tumors (RECIST) version 1.1
5. Patients with SMO overexpression by IHC
6. Patients are willing and able to comply with the protocol for the duration of thestudy including undergoing treatment and scheduled visits and examinations.
7. ECOG performance status 0-1.
8. Patients must have a life expectancy ≥ 3 months from proposed first dose date.
9. Patients must have acceptable bone marrow, liver and renal function measured within 28days prior to administration of study treatment as defined below:

• Haemoglobin ≥9.0 g/dL (transfusion allowed)
• Absolute neutrophil count (ANC) ≥ 1.5 x 109/L
• White blood cells (WBC) > 3 x 109/L
• Platelet count ≥100 x 109/L (transfusion allowed)
• Total bilirubin ≤ 1.5 x institutional upper limit of normal (ULN) (does notinclude patients with Glibert's disease)
• AST (SGOT)/ALT (SGPT) ≤ 2.5 x institutional upper limit of normal unless livermetastases are present in which case it must be ≤ 5x ULN
• Serum creatinine ≤1.5 x institutional ULN

10. Negative urine or serum pregnancy test within 28 days of study treatment, confirmedprior to treatment on day 1. for women of childbearing potential.
11. Provision of consent for mandatory biopsy at progression (fresh frozen will bemandatory if clinically feasible)
12. Provision of archival or fresh tissue sample at baseline (fresh frozen will bemandatory if clinically feasible)

Exclusion Criteria: Patients will be excluded from the study if they meet any of the following criteria:

1. Are currently enrolled in, or discontinued within the last 21 days from, a clinicaltrial involving an investigational product or non-approved use of a drug or device, orconcurrently enrolled in any other type of medical research judged not to bescientifically or medically compatible with this study.
2. Any previous treatment with Hedgehog pathway inhibitor
3. Patients with second primary cancer, except: adequately treated non-melanoma skincancer, curatively treated in-situ cancer of the cervix, or other solid tumourscuratively treated with no evidence of disease for ≤5 years.
4. HER2 positive patients (defined by HER2 3+ by immunohistochemistry or HER2 SISH +)
5. Patients unable to swallow orally administered medication.
6. Treatment with any investigational product during the last 21 days before theenrollment (or a longer period depending on the defined characteristics of the agentsused).
7. Patients receiving any systemic chemotherapy, radiotherapy (except for palliativereasons), within 3 weeks from the last dose prior to study treatment (or a longerperiod depending on the defined characteristics of the agents used). The patient canreceive a stable dose of bisphosphonates or denusomab for bone metastases, before andduring the study as long as these were started at least 4 weeks prior to treatment.
8. With the exception of alopecia, any ongoing toxicities (>CTCAE grade 1) caused byprevious cancer therapy.
9. Intestinal obstruction or CTCAE grade 3 or grade 4 upper GI bleeding within 4 weeksbefore the enrollment.
10. Resting ECG with measurable QTcB > 480 msec on 2 or more time points within a 24 hourperiod or family history of long QT syndrome.
11. Patients with cardiac problem as follows: Atrial fibrillation with a ventricular rate >100 bpm on ECG at rest , Symptomatic heart failure (NYHA grade II-IV), Prior orcurrent cardiomyopathy, Severe valvular heart disease, Uncontrolled angina (CanadianCardiovascular Society grade II-IV despite medical therapy), Acute coronary syndromewithin 6 months prior to starting treatment
12. Female patients who are breast-feeding or child-bearing and Male or female patients ofreproductive potential who are not employing an effective method of contraception
13. Any evidence of severe or uncontrolled systemic disease, active infection, activebleeding diatheses or renal transplant, including any patient known to have hepatitisB, hepatitis C or human immunodeficiency virus (HIV) (HBV carrier is allowed)