PD-1 Antibody Adjuvant Therapy for GC Patients With MSI-H After D2 Radical Surgery

Launched by FUDAN UNIVERSITY · Jul 20, 2022

Keywords

ClinConnect Summary

This clinical trial is studying a new treatment approach for patients with a specific type of gastric cancer called MSI-H after they have undergone a major surgery known as D2 radical gastrectomy. The trial will compare the effects of a PD-1 monoclonal antibody immunotherapy, which is a type of treatment that helps the immune system fight cancer, to standard chemotherapy and a follow-up observation with no additional treatment. Researchers believe that patients with MSI-H gastric cancer may do better with immunotherapy rather than traditional chemotherapy, which hasn’t worked as well for them in the past.

To participate in this trial, patients need to be between 18 and 75 years old and have had surgery for stage II-IIIc gastric adenocarcinoma with the MSI-H status confirmed. They should not have received any prior treatments like chemotherapy or radiation and must meet certain health criteria, ensuring they are in good enough shape to participate. During the trial, participants will receive either the new immunotherapy, standard chemotherapy, or will be observed without treatment. The goal is to see if the new treatment improves their chances of recovery compared to the other options.

Gender

ALL

Eligibility criteria

• Inclusion Criteria:
• • 1. Written (signed) informed consent;
• • 2. D2 radical gastrectomy for gastric cancer
• • 3. Postoperative pathology confirmed II-IIIc stage gastric adenocarcinoma with dMMR/MSI-H status;
• • 4. Female or male, 18-75 years;
• • 5. ECOG 0-1, no surgery contraindications;
• • 6. No initial treatment (radiotherapy / chemotherapy / immunotherapy).;
• • 7. Esophagus not involved ≥ 3cm;
• • 8. Basic diseases without thyroid and cardiopulmonary dysfunction
• • 9. Adequate hematological, liver, renal and coagulation function; 1) Platelet (PLT) count ≥100,000 /mm3; 2) Neutrophil count (ANC) ≥1,500 /mm3; 3) Hemoglobin (Hb) level ≥9.0 g/dl; 4) International normalized ratio (INR) ≤1.5; 5) Prothrombin time (PT) and activated partial thromboplastin time (APTT) ≤1.5×ULN; 6) Glycosylated hemoglobin (HbA1c) \<7.5%; 7) Total bilirubin (TBIL) level ≤1.5×ULN; 8) Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) level ≤2.5×ULN (≤5×ULN in case of liver metastasis); 9) Alkaline phosphatase level ≤2.5×ULN (≤5×ULN in case of liver metastasis); 10) Serum creatinine (Cr) level ≤1.5×ULN and creatinine clearance ≥60 ml/min; 11) Thyroid stimulating hormone (TSH) ≤ULN; 12) Normal serum free thyroid hormone (T4); 13) Normal serum free triiodothyronine (T3); 14) Serum amylase ≤1.5×ULN; 15) Lipase ≤1.5×ULN.
• • 10. Females of child bearing age must have a negative pregnancy test, and have to take contraception measures and avoid breast feeding during the study and for 3 months after the last dose; male subjects must agree to taken contraception measures during the study and for 3 months after the last dose.
• Exclusion Criteria:
• • 1. Known allergy to study drug or excipients, or allergy to similar drugs;
• • 2. Patients with active malignant tumor in recent 2 years, except the tumor studied in this research or cured localized tumor like resected basal cell or squamous cell skin cancer, superficial bladder cancer, cervical or breast carcinoma in situ;
• • 3. Uncontrollable pleural effusion, pericardial effusion, or ascites in 2 weeks before recruitment;
• • 4. The patient has a serious history of heart disease, including congestive heart failure, uncontrollable arrhythmia, unstable angina pectoris, myocardial infarction, severe heart valve disease and intractable hypertension;
• • 5. Unable to swallow study drug;
• • 6. Prior chemotherapy, radiotherapy for gastric cancer;
• • 7. Prior therapy with a PD-1, anti-PD-Ligand 1 (PD-L1) or CTLA-4 agent;
• • 8. Prior therapy with tyrosine kinase inhibitor within 2 weeks.
• • 9. Concurrent medical condition requiring the use of cortisol (\>10mg/day Prednisone or equivalent dose) or other systematic immunosuppressive medications within 14 days before the study treatment. Except: inhalation or topical corticosteroids. Doses \> 10 mg/day prednisone or equivalent for replacement therapy;
• • 10. Have vaccination with attenuated live vaccines within 4 weeks prior to initiation of the study treatment or plan to vaccinate during the study;
• • 11. Poorly controlled hypertension or diabetes;
• • 12. With bleeding tendency, or evident hemoptysis or other hemorrhagic events (e.g. gastrointestinal hemorrhage, hemorrhagic gastric ulcer) within 2 months prior to initiation of study treatment, or presence of hereditary or acquired bleeding or thrombotic tendency (e.g. hemophilia, coagulopathy, thrombocytopenia, etc.), or current/long-term thrombolytic or anticoagulant therapy (except aspirin ≤100 mg/day);
• • 13. Present or history of any autoimmune disease;
• • 14. With active tuberculosis or receiving previous anti-tuberculosis therapy within one year;
• • 15. Diagnosed with interstitial pneumonia, non-infectious pneumonia, pulmonary fibrosis, acute lung disease;
• • 16. Pregnancy or breast feeding;
• • 17. Human immunodeficiency virus (HIV) infection (HIV antibody positive), or active hepatitis C virus (HCV) infection (HCV antibody positive), or active hepatitis B virus (HBV) infection (HBsAg or HBcAb positive, and HBV-DNA ≥2000 IU/ml (copies/ml)), or other severe infection requiring systemic antibiotic treatment, or unexplained body temperature \>38.5℃ during screening period/before study treatment;
• • 18. Patients with other severe acute or chronic conditions that may increase the risk of participation in the study and study treatment, or may interfere with interpretation of study results, and judged by the investigator as not suitable for participation in this clinical trial.