tislelizumab plus anlotinib for immunotherapy resistant gastrointestinal cancer

Conditions: Gastric Cancer; Colo-rectal Cancer

Summary: immunotherapy acquired resistance was observed in clinical practice. the investigators intended to add anlotinib to pd-1 inhibitors, hoping reverse the resistance.

anti-angiogenesis seems have positive effects on tumor immune microenvironment. the combination of pd-1/pd-l1 inhibitors and tkis exhibited favorable efficacy on gastrointestinal malignancies. here the investigators want to examine the efficacy and survival benefit from the combination therapy to pd-1 acquired resistance patients, which turns out to be critical issues in recent years.

Eligibility criteria:
inclusion criteria: * ecog scored 0 or 1, ≥18 years old, expected os≥3 months; * histology confirmed unresectable or metastatic gastric/gastroesophageal junction adenocarcinoma 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 following conditions: i) there was no severe immune-related adverse events, ii) the duration between tumor progression and screening should be 3-12 weeks, iii) the best evaluation results should be pr or cr when receiving pd-1/pd-l1 treatment but progression was confirmed in the latest evaluation, iv) patients were diagnosed with special pathology subtypes, that are sensitive to immunotherapy, such as dmmr, msi-h tumors, or gastric cancer with pd-l1 cps≥10, pfs≥6 months in the last treatment line; * laboratory test should meet following standard: i) hb≥90g/l, neutrophils≥1.5\*10\^9/l, plt≥100\*10\^9, ii) alt and ast\ 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 participants should 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 prednisone equally), ctx; * conditions affect oral absorption (eg: dysphagia, intestinal obstruction; chronic diarrhea); * uncontrolled pleural effusion, hydropericardium and seroperitoneum; * brain metastasis; * received other anti-tumor treatment in past 3 weeks, eg: surgery, radiotherapy, target therapy, immunotherapy, and traditional chinese therapy (target therapy less than 5 half-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) hiv positive; 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 society factors.