Tislelizumab Plus Anlotinib for Immunotherapy Resistant Gastrointestinal Cancer

Gastric Cancer Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04777162
• Other study ID #: Tislelizumab plus Anlotinib
• Status: Recruiting
• Phase: Phase 2
• Start date: March 2021
• Est. completion date: May 2023

Study information

• Verified date: March 2021
• Source: Peking University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 40
• Est. completion date: May 2023
• Est. primary completion date: January 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Colo-rectal Cancer
• Gastric Cancer
• Rectal Neoplasms
• Stomach Neoplasms

Intervention

Drug:
• Tislelizumab
For included participants, tislelizumab would be administrated 200mg q3w iv.
• Anlotinib
Patients will be administrated with Anlotinib 12mg p.o. d1-d14 q3w.

Locations

Country	Name	City	State
China	Beijing Cancer Hospital	Beijing	Beijing

Sponsors (1)

Lead Sponsor	Collaborator
Peking University

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	objective response rate	the rate of patients reached PR or CR based on RECIST 1.1	2 years
Secondary	progression-free survival	the time from recruiting to death or progression	Up to 2 years
Secondary	overall survival	the time from recruiting to death	Up to 2 years