| Eligibility |
Inclusion Criteria:
1. Written informed consent and any locally-required authorization obtained from the
subject prior to performing any protocol-related procedures, including screening
evaluations
2. Age >= 19 years at time of study entry
3. Histologically proven gastric cancer
4. Unresectable or recurrent
5. Previous exposure to 1 palliative chemotherapy for their unresectable or recurrent
cancer (Relapse within 6 months of completion of adjuvant/neoadjuvant chemotherapy
containing 5-Fluoropyrimidine monotherapy or 5-fluoropyrimidine and platinum based
regimen is considered as first-line therapy)
6. Should have measurable lesion based on RECIST V1.1
7. Without previous expose to immune-oncology agents including anti-CTLA4, anti-PD1,
anti-PDL1, etc
8. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 , and body
weight >30 kg
9. Life expectancy of > 12weeks
10. Adequate normal organ and marrow function as defined below:
- Haemoglobin = 10.0 g/dL without transfusion within 28 days
- No features of MDS/AML
- Absolute neutrophil count (ANC) = 1.5 x 109/L (> 1500 per mm3)
- Platelet count = 100 x 109/L (>100,000 per mm3)
- Serum bilirubin = 1.5 x institutional upper limit of normal (ULN). <<This will
not apply to subjects with confirmed Gilbert's syndrome (persistent or recurrent
hyperbilirubinemia that is predominantly unconjugated in the absence of hemolysis
or hepatic pathology), who will be allowed only in consultation with their
physician.>>
- 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 CL>51 mL/min by the Cockcroft-Gault formula (Cockcroft and Gault
1976) or by 24-hour urine collection for determination of creatinine clearance:
11. Female subjects must either be of non-reproductive potential or must have a negative
serum pregnancy test upon study entry.
Evidence of post-menopausal status or negative urinary or serum pregnancy test for
female pre-menopausal subjects. Women will be considered post-menopausal if they have
been amenorrheic for 12 months without an alternative medical cause. The following
age-specific requirements apply:
12. Subject is willing and able to comply with the protocol for the duration of the study
including undergoing treatment and scheduled visits and examinations including follow
up.
Exclusion Criteria:
1. Involvement in the planning and/or conduct of the study (applies to both AstraZeneca
staff and/or staff at the study site)Previous enrollment or randomization in the
present study
2. Participation in another clinical study with an investigational product during the
last 3weeks
3. Any previous treatment with a PD1 or PD-L1 inhibitor, including durvalumab
4. Receipt of the last dose of anti-cancer therapy (chemotherapy, immunotherapy,
endocrine therapy, targeted therapy, biologic therapy, tumor embolization, monoclonal
antibodies, other investigational agent) 28 days prior to the first dose of study drug
(14 days prior to the first dose of study drug for subjects who have received prior
TKIs [e.g., erlotinib, gefitinib and crizotinib] and within 6 weeks for nitrosourea or
mitomycin C). (If sufficient wash-out time has not occurred due to the schedule or PK
properties of an agent, a longer wash-out period may be required.)
5. Brain metastases or spinal cord compression unless the patient is stable
(asymptomatic; no evidence of new or emerging brain metastases; and stable and off
steroids for at least 14 days prior to start of study treatment). Following
radiotherapy and/or surgery of the brain metastases subjects must wait 4 weeks
following the intervention and before randomisation with imaging to confirm stability.
6. Mean QT interval corrected for heart rate (QTc) =470 ms calculated from 3
electrocardiograms (ECGs) using Frediricia's Correction
7. Current or prior use of immunosuppressive medication within 14days before the first
dose of durvalumab, with the exceptions of intranasal and inhaled corticosteroids or
systemic corticosteroids at physiological doses, which are not to exceed 10 mg/day of
prednisone, or an equivalent corticosteroid
8. Any unresolved toxicity NCI CTCAE Grade =2 from previous anticancer therapy with the
exception of alopecia, vitiligo, and the laboratory values defined in the inclusion
criteria
-Subjects with Grade =2 neuropathy will be evaluated on a case-by-case basis after
consultation with the Study Physician.
Subjects with irreversible toxicity not reasonably expected to be exacerbated by
treatment with durvalumab may be included only after consultation with the Study
Physician.
9. Any prior Grade =3 immune-related adverse event (irAE) while receiving any previous
immunotherapy agent, or any unresolved irAE >Grade 1
10. Active or prior documented autoimmune or inflammatory disorders (including
inflammatory bowel disease [eg, colitis or Crohn's disease], diverticulitis [with the
exception of diverticulosis], systemic lupus erythematosus, Sarcoidosis syndrome, or
Wegener syndrome [granulomatosis with polyangiitis, Graves' disease, rheumatoid
arthritis, hypophysitis, uveitis, etc]). The following are exceptions to this
criterion:
- Subjects with vitiligo or alopecia
- Subjects with hypothyroidism (eg, following Hashimoto syndrome) stable on hormone
replacement
- Any chronic skin condition that does not require systemic therapy
- Subjects without active disease in the last 5 years may be included but only
after consultation with the study physician
- Subjects with celiac disease controlled by diet alone
11. Active or prior documented inflammatory bowel disease (e.g., Crohn's disease,
ulcerative colitis)
12. History of primary immunodeficiency
13. History of allogeneic organ transplant
14. History of hypersensitivity to durvalumab or any excipient
15. History of hypersensitivity to the combination or comparator agent
16. Active infection including tuberculosis (clinical evaluation that includes clinical
history, physical examination and radiographic findings, and TB testing in line with
local practice), hepatitis B (known positive HBV surface antigen (HBsAg) result),
hepatitis C, or human immunodeficiency virus (positive HIV 1/2 antibodies). Subjects
with a past or resolved HBV infection (defined as the presence of hepatitis B core
antibody [anti-HBc] and absence of HBsAg) are eligible. Subjects positive for
hepatitis C (HCV) antibody are eligible only if polymerase chain reaction is negative
for HCV RNA.
17. History of leptomeningeal carcinomatosis
18. Receipt of live attenuated vaccination within 30 days prior to study entry or within
30 days of receiving durvalumab
19. Female subjects who are pregnant or breastfeeding or male or female subjects of
reproductive potential who are not willing to employ effective birth control from
screening to 90 days after the last dose of durvalumab monotherapy.
20. Any condition that, in the opinion of the investigator, would interfere with
evaluation of study treatment or interpretation of patient safety or study results
21. Symptomatic or uncontrolled brain metastases requiring concurrent treatment, inclusive
of but not limited to surgery, radiation and/or corticosteroids.
22. Subjects with uncontrolled seizures.
23. Features of MDS/ AML
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