Tislelizumab Plus Anlotinib for Immunotherapy Resistant Gastrointestinal Cancer

Peking University

Status and phase

Unknown

Phase 2

Conditions

Gastric Cancer

Colo-rectal Cancer

Treatments

Drug: Anlotinib

Drug: Tislelizumab

Study type

Interventional

Funder types

Other

Identifiers

NCT04777162

Tislelizumab plus Anlotinib

Details and patient eligibility

About

Immunotherapy acquired resistance was observed in clinical practice. The investigators intended to add anlotinib to PD-1 inhibitors, hoping reverse the resistance.

Full 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.

Enrollment

40 estimated patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

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.