Gastric/gastro- Esophageal Junction Adenocarcinoma
Conditions
Interventions
Test group:IBI343 + sintilimab
Sponsors
First Affiliated Hospital of Anhui Medical University
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Inclusion criteria
Inclusion criteria: 1. Sign the Informed Consent Form (ICF), willing and able to comply with the visit and related procedures stipulated in the program. 2. Histopathologically confirmed unresectable locally advanced, recurrent or metastatic G/GEJ AC. 3. Part 1&2: Patients who have previously received first-line platinum + fluorouracil therapy have failed or are intolerant (if the disease has not progressed, platinum and fluorouracil drugs are allowed to be used sequentially). 4. At least 1 measurable lesion (no previous radiotherapy) according to RECIST v1.1. (Accurate measurement by computed tomography (CT) or magnetic resonance imaging (MRI (preferred intravenous contrast agent) at baseline shows that its length diameter is = 10 mm (except for lymph nodes, the short axis of the lymph node must be =15 mm), the target lesion diameter is = twice the thickness of the imaging layer, and the lesion is suitable for repeated and accurate measurement.) A lesion located in a previously irradiated area clearly demonstrates progression to RECIST V1.1 criteria, the lesion can be considered measurable). 5. Age =18 years old, no gender limit. 6. According to the Eastern Cooperative Oncology Group Performance Status (ECOG PS) score of 0 or 1. 7. Expected survival= 12 weeks. 8. Have adequate bone marrow and organ function: a.Blood routine: ANC=1.5×109/L; platelet count= 100×109/L; Hemoglobin content =9.0 g/dL, subjects should not receive blood transfusion products (including red suspension, plateletpheresis, cryoprecipitate, etc.), erythropoietin, Granulocyte-Colony Stimulating Factor (G-CSF), or granulocyte-macrophage colony-stimulating factor ( Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF) treatment; b. Liver function: TBIL=1.5×ULN (TBIL=3×ULN allowed in subjects with Gilbert syndrome); ALT and AST = 2.5× ULN in subjects without liver metastases, ALT and AST=5×ULN in subjects with liver metastases; albumin= 30 g/L; c. Renal function: creatinine clearance= 60 mL/min (using the Cockcroft-Gault formula) Urine protein <2+ or 24-hour total urine protein volume<1 g; d. Coagulation function: International Normalized Ratio (INR) = 1.5 and Activated Partial Thromboplastin Time (APTT) = 1.5 × ULN (anticoagulant therapy is allowed and the coagulation function is within the above range) subjects). 9. Female subjects of childbearing age or male subjects whose partners are women of childbearing age need to use effective contraception throughout the treatment period and within 6 months after the treatment period. 10. Pathological tissue test confirmed as *CLDN18.2 positive. 11. Encourage the provision of sectional PD-L1 CPS expression assays. Remark: *CLDN18.2 positive: defined as Claudin18.2 immunohistochemical membrane staining intensity =2+ in =40% of tumor cells, receiving previous test results and research center test results. For CLDN18.2 expressed proportions, sponsors can dynamically adjust to newly generated data during the study
Exclusion criteria
Exclusion criteria: Subjects will not be eligible for inclusion in this study if any of the following criteria are met: 1. Are participating in another interventional clinical study, other than an observational (non-interventional) clinical study or at survival follow-up of an interventional study. 2. Receiving cytochrome P450 3A4 (CYP3A4) strong inhibitor therapy within 2 weeks or 5 half-lives (whichever is longer) prior to the first dose of the study drug. 3. Receive the last anti-tumor treatment 4 weeks before the first administration of the study drug or within 5 half-lives of the anti-tumor treatment drug (whichever is shorter). 4. Have received therapeutic or palliative radiation therapy within 2 weeks prior to the first administration of the study drug. 5. Biliary stenting within 7 days prior to first study drug use. 6. Plan to receive other antitumor therapy during the drug treatment of this study [palliative radiotherapy is allowed for the purpose of relieving symptoms (such as pain) without affecting the evaluation of efficacy]. 7. Any live vaccine administered within 4 weeks prior to the first administration of the study drug or planned for the duration of the study. 8. Have undergone a major surgical procedure (craniotomy, thoracotomy or laparotomy or other defined by the investigator, excluding needle biopsy) or have an unhealed wound, ulcer, or fracture within 4 weeks prior to the first administration of the study drug; or major surgery is planned for the duration of the study. For palliative care purposes, local surgery for isolated lesions is acceptable. 9. There are toxicities caused by previous treatment that have not recovered to NCI CTCAE v5.0 grade 0 or 1 before the first administration of the study drug (excluding alopecia, fatigue, pigmentation and other toxicities that are not considered to be safety risks according to the investigator's judgment). 10. History of gastrointestinal perforation and/or fistula within 6 months prior to the first administration of the study drug and unresolved by surgical treatment. 11. Presence of pyloric obstruction and/or persistent and repeated vomiting (vomiting = 3 times within 24 hours). 12. After endovascular stenting in the digestive tract [Refers to the muscular duct from the mouth to the canal, including the mouth, pharynx, esophagus, stomach, small intestine (duodenum, jejunum, ileum), large intestine (cecum, appendix, colon, rectum, etc.), and canal] or after endotracheal stenting or tracheal cavity. 13.Symptomatic central nervous system metastases. Subjects with asymptomatic brain metastases (i.e., no neurological symptoms, no need for glucocorticoid treatment, and brain metastases =1.5 cm) or subjects with stable symptoms after treatment of brain metastases need to meet all the following criteria to participate this study: No midbrain, pons, cerebellum, meninges, medulla or spinal cord metastases; clinical status remains stable for at least 4 weeks, clinical evidence confirms no new or expanding brain metastases, corticosteroids are discontinued before the first dose of study drug and anticonvulsant medication for at least 2 weeks. Note: The central nervous system is not a target lesion. 14. Bone metastases at risk of paraplegia. 15.15. Interstitial lung disease that requires steroid treatment, or a history of interstitial lung disease, non-infectious pneumonia, severely impaired lung function or uncontrolled lung disease, such as pulmonary fibrosis, severe radiation pneumon
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Objective Response Rate;Adverse Event;Treatment-Emergent Adverse Event; Adverse Event of Special Interest;Serious Adverse Event; | — |
Secondary
| Measure | Time frame |
|---|---|
| Progression-free Survival;Duration of Response;Disease Control Rate;Time to Response;Overall Survival; | — |
Countries
China
Contacts
Public ContactDu Yingying
First Affiliated Hospital of Anhui Medical University
Outcome results
None listed