Tislelizumab Plus Anlotinib for Immunotherapy Resistant Gastrointestinal Cancer

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

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

Study Overview

• Status: Recruiting
• Conditions: Gastric Cancer; Colo-rectal Cancer
• Intervention / Treatment: Drug: Tislelizumab; Drug: Anlotinib

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.

• Study Type: Interventional
• Enrollment (Anticipated): 40
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100142
      • Recruiting
      • Beijing Cancer Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: tislelizumab+anlotinib; patients will be administrate with dual drugs, tislelizumab plus anlotinib.	Drug: Tislelizumab; For included participants, tislelizumab would be administrated 200mg q3w iv.; Drug: Anlotinib; Patients will be administrated with Anlotinib 12mg p.o. d1-d14 q3w.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
objective response rate	the rate of patients reached PR or CR based on RECIST 1.1	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
progression-free survival	the time from recruiting to death or progression	Up to 2 years
overall survival	the time from recruiting to death	Up to 2 years

Collaborators and Investigators

• Sponsor: Peking University

Study record dates

Study Major Dates

• Study Start (Anticipated): March 1, 2021
• Primary Completion (Anticipated): January 1, 2023
• Study Completion (Anticipated): May 1, 2023

Study Registration Dates

• First Submitted: February 25, 2021
• First Submitted That Met QC Criteria: February 26, 2021
• First Posted (Actual): March 2, 2021

Study Record Updates

• Last Update Posted (Actual): March 4, 2021
• Last Update Submitted That Met QC Criteria: March 2, 2021
• Last Verified: March 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Stomach Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms; Stomach Neoplasms; Rectal Neoplasms
• Other Study ID Numbers: Tislelizumab plus Anlotinib

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No