gastric carcinoma
Conditions
Interventions
Treatment group 1:Patients will receive FS-1502 combined with Srulizumab plus chemotherapy (5-FU/ capecitabine)
Treatment group 2:Patients will receive FS-1502 combined with Srulizumab
Sponsors
Beijing Cancer Hospital
Eligibility
Sex/Gender
All
Age
18 Years to 75 Years
Inclusion criteria
Inclusion criteria: Patients must meet all of the following criteria for admission: 1. Age 18-75 years old, gender is not limited; 2. Locally advanced or metastatic gastric adenocarcinoma confirmed histologically and/or cytologically (including adenocarcinoma of the gastroesophageal junction); 3. Unable to perform radical therapy (tumor cannot be surgically resected) and have received =1 systemic anti-tumor therapy (safe introduction phase) in the past (recurrence or progression within 6 months after the last treatment of adjuvant chemotherapy or neoadjuvant chemotherapy is considered as first-line treatment failure); 4. HER2 test results are positive or low expression (it is recommended that the central laboratory results prevail) : Her2-positive is defined as: immunohistochemical (IHC) 3+ or IHC2+ and fluorescence in situ hybridization (FISH) +. Low HER2 expression was defined as: immunohistochemistry (IHC) 1+ or IHC2+ and fluorescence in situ hybridization (FISH) -; 5. All subjects need to provide tumor tissue samples (preferably within 2 years before the first study) to the central laboratory for HER2 expression detection; enrolled subjects also need to provide tumor tissue samples and blood samples to the central laboratory for PD-L1 expression, bMSI and bTMB status detection; 6. According to the evaluation criteria for the efficacy of solid tumors (RECIST 1.1), there should be at least one measurable lesion (the cavity structure such as stomach and esophagus should not be used as a measurable lesion), and the measurable lesion should not have received local treatment such as radiotherapy (the lesion located in the previous radiotherapy area can also be selected as a target lesion if it is confirmed to have progressed); 7. Physical status score of 0 or 1 from the Eastern cooperative oncology group (ECOG) (see Annex 3); 8. Expected survival >=3 months; 9. The function of vital organs meets the following requirements: (No blood components and cell growth factors are allowed to be used within 14 days before the screening period) neutrophil absolute value >=1.5×10^9/L; Hemoglobin >=90g/L; Platelet >=100×10^9/L; Serum total bilirubin =30g/L; Serum creatinine =50mL/ min (calculated by Cockroft-Gault formula); Blood potassium >=3.5 mmol/L; Activated partial thromboplastin time (APTT), prothrombin time (PT) and International Normalized ratio (INR) <=1.5 × ULN. Urinary protein <=1+ or 24-hour urinary protein quantity < 1.0g; 10. Female patients with fertility were enrolled as follows: Serum pregnancy test results within 7 days prior to enrollment must be negative; consent to use contraception with an annual failure rate of < 1% or to remain abstinent (abstaining from heterosexual intercourse) for at least 120 days from the signing of the informed consent to the last administration of the investigatory drug, At least 6 months after the last dose of chemotherapy drugs) (contraceptive methods with an annual failure rate of < 1% include bilateral tubal ligation, male sterilization, proper use of hormonal contraceptives that inhibit ovulation, hormone-releasing intrauterine devices and copper intrauterine devices); Do not breastfeed. 11. Male patients must: consent to
Exclusion criteria
Exclusion criteria: Patients who meet any of the following conditions are not allowed to enter this clinical study: 1. A history of gastrointestinal perforation and/or fistula within 6 months prior to initial medication; 2. Active bleeding or a high risk of bleeding/perforation, such as severe open wounds or peptic ulcers within 28 days prior to enrollment; A history of >= grade 3 gastrointestinal or non-gastrointestinal fistulas; Clinically significant bleeding disorder, vasculitis, or significant gastrointestinal bleeding within 12 weeks prior to enrollment; 3. Uncontrolled pleural effusion, pericardial effusion or ascites requiring repeated drainage; 4. Known allergy to any excipient of FS-1502 and any active ingredient or excipient in Srulizumab, 5-FU/ capecitabine; 5. Received any of the following treatments: a. Previously received anti-HER2 antibody conjugated drug therapy; b. Received any investigational drug within 4 weeks or 5 drug half-lives (whichever is shorter) prior to first use of the investigational drug; c. Enrolling in another clinical study at the same time, unless it is an observational (non-interventional) clinical study or an interventional clinical study follow-up; d. Received chemotherapy, small-molecule drug targeted drug therapy, radiotherapy, etc. within 14 days or 5 half-lives (whichever is shorter) prior to the first use of the investigational drug; Patients who had received tumor immunotherapy or macromolecular monoclonal anti-tumor drugs within 4 weeks prior to initiation of administration (except adjuvant anti-tumor therapy with Chinese medicine); e. Patients requiring systemic treatment with corticosteroids (equivalent dose > 10 mg prednisone per day) or other immunosuppressants within 2 weeks prior to initial use of the study drug, except for corticosteroids for the prevention of allergy and nausea and vomiting. Other special circumstances, need to communicate with the sponsor. In the absence of active autoimmune disease, inhaled or topical steroids and adrenocortical hormone replacement at doses not exceeding the therapeutic dose of prednisone 10mg/ day are permitted; f. Those who have received anti-tumor vaccine or have received live or attenuated vaccine within 4 weeks before the first administration of the investigational drug; g. Has undergone or plans to undergo major surgery or serious injury within 4 weeks prior to the first use of the study drug; 6. The toxicity of previous anti-tumor therapy did not return to <=CTCAE Class 1 (except alopecia and pigmentation) or the level specified in the inclusion/exclusion criteria; 7. Pial metastasis, spinal cord metastasis, brain stem metastasis and other patients with clinical symptoms of brain parenchymal metastasis. Subjects with parenchymal metastases (except brainstem) meeting the following three criteria were admitted to the study: Have been treated for brain metastases and have been stable for at least 3 months; No disease progression and no new or expanded brain metastases were determined by imaging during the 4 weeks prior to administration; • No neurological symptoms, no need for steroid treatment; 8. Active autoimmune diseases (such as interstitial pneumonia, colitis, hepatitis, hypophysitis, vasculitis, nephritis, hyperthyroidism, hypothyroidism, including but not limited to these diseases or syndromes); History of interstitial pneumonia; Except for autoimmune mediated hypothyroidism treated with stable doses of thyroid replacement hormone and type 1 diabetes trea
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Occurrence of DLT (security introduction period);Objective response rate (ORR); | — |
Secondary
| Measure | Time frame |
|---|---|
| Progression free survival, PFS;Overall survival, OS;Duration of response, DOR;Disease control rate, DCR;Occurrence and frequency of adverse events (AE) and serious adverse events (SAE), toxicity grade evaluated according to NCI-CTCAE version 5.0; ? Proportion of patients undergoing dose adjustment or discontinuation due to drug toxicity;;PK parameters of FS-1502, total resistance and MMAF. Exploratory index; | — |
Countries
China
Contacts
Public ContactLin Shen
Department of Gastroenterology, Beijing Cancer Hospital
Outcome results
None listed