PD-1 Antibody for The Prevention of Adenomatous Polyps and Second Primary Tumors in Lynch Syndrome Patients

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Brief Title

PD-1 Antibody for The Prevention of Adenomatous Polyps and Second Primary Tumors in Lynch Syndrome Patients

Official Title

PD-1 Antibody for the Prevention of Adenomatous Polyps and Second Primary Tumors in Patients With Lynch Syndrome: An Open-label, Multicenter, Randomized Controlled Clinical Trial

Brief Summary

      This study aims to explore the role of PD-1 Antibody in preventing adenomatous polyps and
      second primary tumors in patients with Lynch Syndrome. There two arms, one is the
      experimental arm (PD-1 antibody prevention group) and the other is the control arm (routine
      follow-up group). For the experimental group, Tripleitriumab (PD-1 antibody) is given every 3
      months for a year.

Detailed Description

      Lynch syndrome (LS) is a hereditary cancer syndrome that causes the majority of hereditary
      CRC and approximately 3% of all CRC. LS significantly increases the risk for an individual to
      develop CRC during their lifetime. Individuals with LS also have an increased risk to develop
      extracolonic cancers, including endometrial, gastric, ovarian, upper urinary tract, small
      bowel, biliary tract, CNS, and certain types of skin cancer. Given the hereditary nature of
      this syndrome, preventing second primary tumors in patients with Lynch Syndrome after surgery
      to the primary site is very important.

      The purpose of this study is to prevent adenomatous polyps and second primary tumors using
      PD-1 antibody (Tripleitriumab) in patients with Lynch Syndrome.

      The primary outcome of this study is the incidence of intestinal adenomatous polyps and
      secondary primary tumors. The secondary outcomes are the incidence of colorectal adenomatous
      polyps greater than 1cm, incidence of high-grade colorectal polyps, treatment-related adverse
      events, disease-free Survival and overall Survival.

      There are two groups: the PD-1 antibody prevention group and the routine follow-up group. For
      the PD-1 antibody prevention group, participants will receive Toripalimab 240mg IV every 3
      months for a year. For the routine follow-up group, there is no drug intervention.

      This whole study will take 5 years: the first year for recruiting and the latter four years
      for follow-up.

Study Phase

Phase 3

Study Type


Primary Outcome

The percentage of patients from randomization to the first appearance of one of the following: adenomatous polyps or second primary tumors

Secondary Outcome

 The percentage of patients developing polyps greater than 1cm within 5 years from randomization


Lynch Syndrome


PD-1 Antibody

Study Arms / Comparison Groups

 Prevention group
Description:  Toripalimab: 240mg IV every 3 months for a year


* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information

Recruitment Status


Estimated Enrollment


Start Date

November 1, 2020

Completion Date

December 31, 2025

Primary Completion Date

December 31, 2023

Eligibility Criteria

        Inclusion Criteria:

          1. Lynch syndrome with germline variants of MLH1, MSH2, or EPCAM (pathogenic or likely
             pathogenic variants)

          2. Necessary treatments have been done, such as surgery, chemotherapy, radiation therapy,

          3. Have a resection, including right hemicolectomy, left hemicolectomy, sigmoid
             colectomy, or anterior resection of rectal cancer, or endoscopic adenoma resection

          4. Aged 18-70 years old

          5. Eastern Cooperative Oncology Group (ECOG) performance score of 0 to 1

          6. White blood cell (WBC) > 4000/mm3, Platelet count >100000/mm3, HB >10 g/dL

          7. Serum glutamic-oxaloacetic transaminase (SGOT) < 1.5 × the upper limit of normal
             (ULN), Serum glutamic pyruvic transaminase (SGPT) < 1.5 × ULN prior to randomization,
             Total bilirubin (TBIL) < 1.5 mg/dL

          8. Serum creatinine (Scr) <1.8 mg/dL

        Exclusion Criteria:

          1. Lynch syndrome with germline variants of MSH6 and PMS2

          2. Previous immunotherapy has been taken, such as anti-PD-1, anti-PD-L1, etc.

          3. Long-term use of aspirin

          4. Suffering from autoimmune diseases

          5. Active infection with hepatitis B or hepatitis C (high copy number of viral DNA) or
             human immunodeficiency virus (HIV)

          6. Other clinically serious active infections (NCI-CTC 4.0)

          7. With cachexia or organ dysfunction

          8. Suffering from seizures requiring treatment (such as steroids or antiepileptic

          9. Unable to participate or complete the study due to substance abuse, or medical,
             psychological, or social disorder

         10. Known allergy to any drugs in this study

         11. Pregnant or nursing women, or women of childbearing potential who are not using
             adequate contraception

         12. Any unstable condition or situation that could compromise the safety and compliance of

         13. Failure to sign an informed consent form




18 Years - 70 Years

Accepts Healthy Volunteers



Peirong Ding, MD, Ph D, 00862087343124, [email protected]

Location Countries


Location Countries


Administrative Informations



Organization ID


Responsible Party

Principal Investigator

Study Sponsor

Sun Yat-sen University


 Second Affiliated Hospital, School of Medicine, Zhejiang University

Study Sponsor

Peirong Ding, MD, Ph D, Study Chair, Sun Yat-sen University

Verification Date

January 2021