Colo-rectal Cancer, Gastric Cancer
Conditions
Brief summary
Immunotherapy acquired resistance was observed in clinical practice. The investigators intended to add anlotinib to PD-1 inhibitors, hoping reverse the resistance.
Detailed description
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.
Interventions
DRUGTislelizumab
For included participants, tislelizumab would be administrated 200mg q3w iv.
DRUGAnlotinib
Patients will be administrated with Anlotinib 12mg p.o. d1-d14 q3w.
Sponsors
Peking University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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\<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 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| objective response rate | 2 years | the rate of patients reached PR or CR based on RECIST 1.1 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| progression-free survival | Up to 2 years | the time from recruiting to death or progression |
| overall survival | Up to 2 years | the time from recruiting to death |
Countries
China
Outcome results
None listed