Advanced or Recurrent Gastric and Gastroesophageal Junction Cancer

Primary Objective: To compare the treatment effect of nimotuzumab and irinotecan combination with that of irinotecan alone on overall survival. Secondary Objectives: • To compare the treatment effect of nimotuzumab and irinotecan combination with that of irinotecan alone on progression-free survival • To assess the safety and tolerability of nimotuzumab and irinotecan combination therapy compared with irinotecan monotherapy Exploratory Objectives: • To assess pharmacokinetics profile of nimotuzumab • To compare the treatment effect of nimotuzumab and irinotecan combination with that of irinotecan alone on response rate and disease control rate • To assess the expression of human antihumanized antibody • To assess biomarker

DE-766 injection 50 mg/10mL vial

Nimotuzumab

Injection

50 mg / 10 mL

Primary Efficacy Endpoint:
• Overall survival
Secondary Efficacy Endpoints:
• Progression-free survival
Exploratory Efficacy Endpoints:
• Overall response rate
• Disease control rate
Pharmacokinetics Endpoints:
• Pharmacokinetic parameters (Cmax,Tmax, Kel, AUC0-168h, AUCinf, T1/2, CLss,
MRTinf, and Vss)
Safety Endpoints:
• Subject incidence of adverse events
• Changes in laboratory values
Other Exploratory Endpoints:
• Biomarker analyses
• The presence of human antihumanized antibody

Inclusion Criteria
1. Advanced or recurrent subjects with histologically or cytologically confirmed
gastric or gastroesophageal junction adenocarcinoma.
2. Subjects who experienced disease progression during first line or within 6 months
after the last dose of first line therapy. The first line regimen must have
contained a 5-fluorouracil based agent and platinum agent.
3. Subjects who agreed to submit tumor tissue for the assessment of EGFR
expression, EGFR gene amplification and KRAS gene mutation.
4. Subjects with EGFR overexpression (2+ or 3+ in IHC) determined at the central
laboratory.
5. Subjects with assessable by the Response Evaluation Criteria in Solid Tumors
(RECIST) version 1.1. Subjects with only non-target lesions can be eligible.
6. Male or female subjects ≥ 20 years old.
7. Subjects with life expectancy ≥ 3 months at randomization.
8. Subjects with Eastern Cooperative Oncology Group (ECOG) Performance Status
of 1 or 0 at randomization.
9. Subjects must have adequate organ functions as defined below, within 14 days
prior to randomization.
Parameters Laboratory value
White blood cell count ≥ 3000/mm3
AND ≤ 12000/mm3
Absolute neutrophil count ≥ 1500/mm3
Platelet count ≥ 100000/mm3
Hemoglobin ≥ 8.5 g/dL
AST ≤ 100 IU/L
ALT ≤ 100 IU/L
Total bilirubin ≤ 1.5 mg/dL
Serum creatinine ≤ 1.5 mg/dL
10. Subjects must have the following wash out period at randomization.
• Surgery (eg, gastrectomy): 4 weeks, 2 weeks for less invasive surgery,
such as colostomy
• Radiation: 4 weeks
• Chemotherapy and other study drugs: 4 weeks, 2 weeks for
5-fluorouracil-based agents and/or folinate agents, and 6 weeks for
mitomycin
• Trastuzumab: 4 weeks

Exclusion Criteria
1. Subjects who have received irinotecan.
2. Subjects who have received EGFR-directed therapy (eg, cetuximab, erlotinib).
Subjects who have received trastuzumab can be eligible.
3. Other active malignancy within the last 5 years, except for completely resected
nonmelanoma skin cancer or successfully treated in situ carcinoma.
4. Pleural effusion, ascites or pericardial effusion that requires drainage.
5. Subjects with diarrhea (watery stool) at randomization 2)
6. Subjects with ileus at any grade or constipation of ≥ Grade 3 in the Common
Terminology Criteria for Adverse Events (CTCAE).
7. History or clinical evidence of central nervous system metastases.
8. History or clinical evidence of widespread bone metastases.
9. Uncontrolled cardiovascular disease (eg, severe hypertension, history of
myocardial infarction or unstable angina) within 6 months before randomization.
10. Subjects who have active gastrointestinal hemorrhage that requires blood
transfusions within 14 days before randomization.
11. Severe and/or uncontrolled medical conditions.
• Uncontrolled diabetes
• Jaundice
• Intestinal paralysis
• Severe psychosis or psychiatric symptoms
• Severe infection
12. Subjects with known active infection with hepatitis B virus or hepatitis C virus.
Investigator will consider the risk of reactivation triggered by
immunosuppressive therapy of cancer.
13. Subjects with known infection with human immunodeficiency virus.
14. Residual toxicity of ≥ Grade 2 due to the first line treatment, except for Grade 2
peripheral neuropathy and/or alopecia.
15. Known hypersensitivity to any component of the study drugs or polysorbate 80.
16. History or radiological evidence of interstitial pulmonary disease, pulmonary
fibrosis, radiation pneumonitis or drug-induced pneumonitis.
17. Female subjects, who are pregnant or planning to become pregnant, or lactating
until the post treatment follow-up period. Male subjects who are not willing to
use adequate contraceptive methods until the post treatment follow-up period.
18. Other subjects who are considered to be unsuitable for the study by investigator.