gastric/gastroesophageal junction adenocarcinoma
Conditions
Interventions
Group 1:2mg/kg AK104 (Q2W) + low dose radiotherapy
Group 2:4mg/kg AK104 (Q2W) + low dose radiotherapy
Group 3:6mg/kg AK104 (Q2W) + low dose radiotherapy
Cohort A (no serous effusion):Range of radiotherapy: tumor involved field + recommended dose AK104
Cohort B (with serous effusion):Range of radiotherapy: whole abdomen + recommended dose AK104
Sponsors
The Affiliated Drum Tower Hospital to Medical School of Nanjing University
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Inclusion criteria
Inclusion criteria: 1. Subjects can understand the informed consent, voluntarily participate in and sign the informed consent. 2. Subject shall be at least 18 years old on the date of signing the informed consent. 3. Physical State Score (ECOG) of the Eastern Oncology Consortium 0-1. 4. Predicted survival >=12 weeks. 5. Histologically or cytologically confirmed metastatic or locally advanced unresectable gastric or gastroesophageal junction adenocarcinoma. 6. Subjects with first-line or standard treatment failure (disease progression after treatment or intolerability of toxic and side effects of treatment) or no effective treatment. 7. At least one evaluable lesion at baseline can be used for efficacy evaluation. 8. All subjects must provide tumor tissue samples that have been on file or freshly obtained within 2 years prior to signing the information. At least 5 unstained tumor biopsy samples, preferably newly acquired tumor tissue samples. 9. Aware of the pros and cons of standardized treatment, but still unwilling to accept standardized treatment. 10. The subject has full organ and bone marrow function, defined as follows: (1) Blood routine: neutrophil count >=1.5x10^9/L, hemoglobin >=8.0g/dL, platelet count >=75x10^9/L; (2) Liver function: total bilirubin <=1.5x upper limit of normal value (ULN), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) of subjects without liver metastasis <=2.5xULN. Requirements for subjects with liver metastasis: ALT and AST<=5xULN; (3) Renal function: serum creatinine (Scr) <=1.5xULN; (4) Full coagulation function: defined as International standardized ratio (INR) <=1.5 or prothrombin time (PT) <=1.5 times ULN; If the subject is receiving anticoagulant therapy, PT should be within the prescribed anticoagulant drug range. 11. Subjects of childbearing age should take appropriate protective measures (contraception or other birth control methods) before enrollment and during the trial. 12. The informed consent has been signed, and the visit and related procedures stipulated by the plan can be complied with.
Exclusion criteria
Exclusion criteria: 1. Uncontrollable pleural effusion, pericardial effusion, and abdominal effusion should be excluded for the dose escalation phase and cohort A (drainage should be performed at least once a month). 2. Subjects had a history of other tumors, except for cervical carcinoma in situ, treated squamous cell carcinoma or bladder epithelial tumors (Ta and TIS), or other malignancies that had received radical treatment (at least 5 years prior to enrollment). 3. Uncontrolled co-occurring diseases, including but not limited to active bacterial or fungal infections, symptomatic congestive heart failure, unstable angina, and arrhythmia. 4. Accompanied by HIV infection or active hepatitis B HBV (HBV DNA>=500IU/ml), hepatitis C. 5. Uncontrolled coronary artery disease or asthma, uncontrolled cerebrovascular disease, or other diseases considered ineligible by the researchers. 6. Subjects with autoimmune diseases or immune deficiencies. 7. Use of immunosuppressive drugs in the 4 weeks prior to the first administration of the study drug, excluding: (1) Intranasal inhaled topical steroid therapy or local steroid injection (such as intra-articular injection); (2) Not more than 10 mg/ day of prednisone or its equivalent physiological dose of systemic corticosteroids; (3) Glucocorticoids are used as preventive drugs for allergic reactions (such as pre-CT medication). 8. Subjects requiring long-term systemic hormonal or any other immunosuppressive medication, excluding inhaled hormonal therapy. 9. Receive live attenuated vaccine within 4 weeks prior to the first administration of the study drug or during the study period. 10. Had major surgery (craniotomy, thoracotomy, or laparotomy) within 4 weeks prior to the first dose of study therapy or expected to require major surgery during the study therapy period. 11. A history of gastrointestinal perforation and/or fistula within the past 6 months, a history of intestinal obstruction (including incomplete intestinal obstruction requiring parenteral nutrition), extensive enterotomy (partial resection of the colon or extensive resection of the small intestine with chronic diarrhea), Crohn's disease, ulcerative colitis, or long-term chronic diarrhea. 12. Subjects with gastrointestinal bleeding or high risk of bleeding during the first 2 weeks of enrollment. 13. Subjects with symptomatic central nervous system metastases requiring clinical intervention. 14. Pregnant and lactating subjects. 15. Systemic treatment with Chinese herbal medicines with anti-tumor indications or with immunomodulatory drugs (including thymosin, interferon, interleukin, etc.) was received within 2 weeks prior to initial administration. 16. Subjects who may be allergic to the investigational drug or any excipients thereof. 17. Subjects unable to administer immunotherapy for social or geographical reasons. 18. Significant weight loss (>=10% weight loss) within the first 6 weeks of enrollment. 19. Any uncertainty affecting subject safety or compliance.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Safety; | — |
Secondary
| Measure | Time frame |
|---|---|
| Objective reponse rate;Disease control rate;Progress-free survival;Duration of response;Overall survival;Pharmacokinetics;Immunology; | — |
Countries
China
Contacts
Public ContactLiu Baorui
The Affiliated Drum Tower Hospital to Medical School of Nanjing University
Outcome results
None listed