Clinical trial NCT04777162: Tislelizumab Plus Anlotinib for Immunotherapy Resistant Gastrointestinal Cancer
Official title: Efficacy and Safety of Tislelizumab Plus Anlotinib in PD-1/PD-L1 Resistant Metastatic Gastric or Colorectal Cancer: a Single Arm Phase II Clinical Trial
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Gastric Cancer
Colo-rectal Cancer
Lead sponsor: Peking University
Sponsor class: OTHER
First posted: 2021-03-02
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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\<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.

Primary outcomes:
measure: objective response rate
timeFrame: 2 years
Secondary outcomes:
measure: progression-free survival
timeFrame: Up to 2 years
measure: overall survival
timeFrame: Up to 2 years
Other outcomes:
Locations:
city: Beijing
country: China
facility: Beijing Cancer Hospital
state: Beijing
Study officials:
References: