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
- Both fluoropyrimidine and platinum agent need to be contained in the prior
- Prior adjuvant or neoadjuvant therapy is counted as 1 regimen, provided that
disease progression occurs within 6 months after the completion of adjuvant or
4. Have the presence of measurable disease as defined by the Response Evaluation Criteria
in Solid Tumors (RECIST) version 1.1
5. Patients with MET amplification.
6. Patients are willing and able to comply with the protocol for the duration of the
study including undergoing treatment and scheduled visits and examinations.
7. Eastern Cooperative Oncology Group 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 28
days 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 not
include patients with Glibert's disease)
- AST (SGOT)/ALT (SGPT) ≤ 2.5 x institutional upper limit of normal unless liver
metastases are present in which case it must be ≤ 5x ULN
- Serum creatinine ≤1.5 x institutional ULN
10. At least one measurable lesion that can be accurately assessed by imaging or physical
examination at baseline and following up visits.
11. Negative urine or serum pregnancy test within 28 days of study treatment, confirmed
prior to treatment on day 1. for women of childbearing potential.
12. Provision of consent for mandatory biopsy at progression (fresh frozen will be
mandatory if clinically feasible)
13. Provision of archival or fresh tissue sample at baseline (fresh frozen will be
mandatory if clinically feasible)
1. Are currently enrolled in, or discontinued within the last 21 days from, a clinical
trial involving an investigational product or non-approved use of a drug or device, or
concurrently enrolled in any other type of medical research judged not to be
scientifically or medically compatible with this study.
2. Any previous treatment with MET inhibitors
3. Patients with second primary cancer, except: adequately treated non-melanoma skin
cancer, curatively treated in-situ cancer of the cervix, or other solid tumours
curatively 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 the
enrollment (or a longer period depending on the defined characteristics of the agents
7. Patients receiving any systemic chemotherapy, radiotherapy (except for palliative
reasons), within 3 weeks from the last dose prior to study treatment (or a longer
period depending on the defined characteristics of the agents used). The patient can
receive a stable dose of bisphosphonates or denusomab for bone metastases, before and
during the study as long as these were started at least 4 weeks prior to treatment.
8. With the exception of alopecia, any ongoing toxicities (>Common Toxicity Criteria for
Adverse Effects grade 1) caused by previous cancer therapy.
9. Intestinal obstruction or Common Toxicity Criteria for Adverse Effects grade 3 or
grade 4 upper GI bleeding within 4 weeks before the enrollment.
10. Resting ECG with measurable QTcB > 480 msec on 2 or more time points within a 24 hour
period or family history of long QT syndrome.
11. Patients with cardiac problem as follows: uncontrolled hypertension (BP ≥150/95 mmHg
despite medical therapy) Baseline Left ventricular ejection fraction below the LLN of
<55% measured by echocardiography or institution's LLN for MUGA, Atrial fibrillation
with a ventricular rate >100 bpm on ECG at rest , Symptomatic heart failure (NYHA
grade II-IV), Prior or current cardiomyopathy, Severe valvular heart disease,
Uncontrolled angina (Canadian Cardiovascular Society grade II-IV despite medical
therapy), Acute coronary syndrome within 6 months prior to starting treatment
12. Female patients who are breast-feeding or child-bearing and Male or female patients of
reproductive potential who are not employing an effective method of contraception
13. Any evidence of severe or uncontrolled systemic disease, active infection, active
bleeding diatheses or renal transplant, including any patient known to have hepatitis
B, hepatitis C or human immunodeficiency virus (HIV)
14. Patients currently receiving (or unable to stop use at least 2 weeks) prior to
receiving the first dose of AZD6094, medications known to be potent inhibitors of
CYP1A2 or CYP3A4, potent inducers of CYP3A4 or CYP3A4 substrates with a narrow