Tislelizumab Plus Anlotinib for Immunotherapy Resistant Gastrointestinal Cancer

Inclusion Criteria:

• ECOG scored 0 or 1, ≥18 years old, expected OS≥3 months;
• Histology confirmed unresectable or metastatic gastric/gastroesophageal junctionadenocarcinoma or colorectal cancer;
• ≥1 evaluable lesion based on RECIST 1.1;
• Patients received PD-1/PD-L1 in the last treatment line, and should meet followingconditions: i) there was no severe immune-related adverse events, ii) the duration between tumorprogression and screening should be 3-12 weeks, iii) the best evaluation resultsshould be PR or CR when receiving PD-1/PD-L1 treatment but progression was confirmedin the latest evaluation, iv) patients were diagnosed with special pathology subtypes,that are sensitive to immunotherapy, such as dMMR, MSI-H tumors, or gastric cancerwith PD-L1 CPS≥10, PFS≥6 months in the last treatment line;
• laboratory test should meet following standard: i) HB≥90g/l, neutrophils≥1.510^9/L,plt≥10010^9, ii) ALT and AST<2.5xULN (5ULN for liver metastatic patients),TBIL≤2×ULN, Cr≤1.5×ULN, and Ccr>50μmol/L iii) APTT, INR and PT≤1.5×ULN iv) LVEF≥50%
• for female participants, Hcg should be negative and both male and female participantsshould have contraception measures
• participants should be informed consent, and voluntary.

Exclusion Criteria:

• received anlotinib or other TKIs previously;
• allergic to other monoclonal antibody before the treatment;
• diagnosed with other malignancy in last five years (cured skin basal carcinoma,prostate cancer or cervical caner in situ were excluded)
• concurrent with other active autoimmune disease;
• any condition that require immune suppressor, such as cortisol (>10mg/d prednisoneequally), CTX;
• conditions affect oral absorption (eg: dysphagia, intestinal obstruction; chronicdiarrhea);
• uncontrolled pleural effusion, hydropericardium and seroperitoneum;
• brain metastasis;
• received other anti-tumor treatment in past 3 weeks, eg: surgery, radiotherapy, targettherapy, immunotherapy, and traditional Chinese therapy (target therapy less than 5half-life period, 5-Fu less than 14 days were excluded);
• concurrent with uncontrolled other diseases, i) hypertension (>150/90mmHg) ii)unstable angina pectoris, ≥ level 2 heart failure, arrhythmia within last 6 months;iii) clinical meaningful liver disease, eg: active HBV/HCV hepatitis; iv) HIVpositive; v) uncontrolled diabetes; vi) urine protein ≥++ or 24h urine protein >1g;
• injected vaccine in past 4 weeks, or administrated with antibiotics;
• investigator assumed improper conditions, such as mental disease, family or societyfactors.