This study is an open label phase 2 study to evaluate the safety and efficacy of Lenvatinib
with Pembrolizumab in the neoadjuvant / adjuvant treatment for Patients with Gastric Cancer.
This study is an open-label, single-arm, single-center, phase 2 clinical trial. Eligible
patients are with previously untreated gastric and gastroesophageal junction adenocarcinoma
as defined by cT2-4 and/or cN+ without evidence of metastatic disease. Patients will receive
3 cycles of 20 mg oral Lenvatinib daily plus 200 mg intravenous Pembrolizumab every 3 weeks
as the neoadjuvant treatment followed by surgery, and then 3 cycles of Lenvatinib plus
Pembrolizumab followed by 11 cycles of Pembrolizumab monotherapy as the adjuvant treatment.
1. Have gastric and gastroesophageal junction adenocarcinoma
2. Untreated and cT2-4 and/or cN+ without evidence of metastatic disease
3. Patients at least 20 years of age on the day of providing consent.
4. Patients with a performance status of 0 or 1 on the Eastern Cooperative Oncology
5. Patients with adequate organ function at the time of enrollment as defined below:
- Neutrophil count ≥1500mm3
- Platelet count ≥10 × 100,000/mm3
- Hemoglobin (Hb) ≥ 9.0 g/dL,
- Total bilirubin ≤1.5 mg/dL
- AST (GOT) and ALT (GPT) ≤ 100 IU/L
- Creatinine ≤1.5 mg/dL
- Urinary protein : It satisfies one of the following (if any of the inspection
criteria are satisfied, other examination may not be carried out) (i) urinary
protein (test paper method) is 2+ or less (ii) Urine Protein Creatinine (UPC)
ratio <3.5 (iii) 24-hour urine protein was measured, urinary protein ≦ 3500 mg
- International normalized ratio (INR) ≤ 1.5
6. Patients who not received a blood transfusion within 14 days of registration.
7. Patients have recovered adverse events associated with radiation and surgical
operation as pretreatment to Grade 1 or less or baseline or less with CTCAE v5.0
excluding stable symptoms. However, adverse events with stable symptoms even with
Grade 2 or higher excluded.
8. Female of childbearing potential who are negative in a pregnancy test within 14 days
before enrollment. Both male and female patients should agree to use an adequate
method of contraception (total abstinence or use of a male condom plus partner use of
contraceptive method [an intrauterine device or hormone releasing system, a
contraceptive implant and an oral contraceptive]) starting with the first dose of
study therapy through 120 days after the last dose of study therapy. Duration will be
determined when the subject is assigned to treatment.
9. Patients capable of taking oral medication.
10. Patients who provided written informed consent to be subjects in this study.
1. Patients who have undergone surgical treatment and radiotherapy within 2 weeks before
2. Patients with hypertension that is difficult to control (systolic blood pressure ≥160
mmHg and diastolic blood pressure ≥90 mmHg) despite treatment with several hypotensive
3. Patients with acute coronary syndrome (including myocardial infarction and unstable
angina), and with a history of coronary angioplasty or stent placement performed
within 6 months before enrollment.
4. Patients with a history of New York Heart Association congestive heart failure of
grade II or above, unstable angina, myocardial infarction.
5. Patients have an addigional active malignancy (except for definitively treated
melanoma in-situ, basal or squamous cell carcinoma of the skin, or carcinoma in-situ
of the cervix) within the past 24 months.
6. Patients have severe (hospitalization required) complications (intenstinal palsy,
intestinal obstruction, pulmonary fibrosis, diabetes difficult to control, heart
failure, myocardial infarction, unstable angina, renal failure, liver failure, mental
disease, cerebrovascular disease etc).
7. Patients with a history of a gastrointestinal perforation and /or gastrointestinal
fistula within 6 months before enrollment.
8. Is infected with active hepatitis B (defined as HBs antigen positive) or hepatitis C.
9. Patients with a history of human immunodeficiency virus (HIV).
10. Patients with a history of (non-infectious) pneumonitis that required steroids or has
11. Patients who are administered live vaccines <30 days before the initiation of
treatment with the investigational drug.
12. Patients with concurrent autoimmune disease, or a history of chronic or recurrent
13. Patients who require systemic corticosteroids (excluding temporary usage for tests,
prophylactic administration for allergic reactions, or to alleviate swelling
associated with radiotherapy) or immunosuppressants, or who have received such a
therapy <14 days before enrollment.
14. Patients have serious non-healing wound, ulcer, or bone fracture.
15. Females who are pregnant or breastfeeding.
16. Patients have no intention to comply with the protocol or cannot comply.
17. Patients were judged unsuitable as subject of this study by investigator.