Toripalimab Plus Bevacizumab and Chemotherapy as Neoadjuvant Therapy in Advanced MSI-H or dMMR Colorectal Cancer

NCT ID: NCT04988191

Last Updated: 2021-08-03

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

PHASE1/PHASE2

Total Enrollment

44 participants

Study Classification

INTERVENTIONAL

Study Start Date

2020-12-24

Study Completion Date

2023-12-24

Brief Summary

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This is a trial investigating the efficacy and safety of Toripalimab combined with bevacizumab and chemotherapy as neoadjuvant therapy in patients with advanced microsatellite instability-high (MSI-H) or DNA mismatch repair-deficient (dMMR) colorectal cancer.

Detailed Description

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Conditions

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Colorectal Carcinoma

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Toripalimab combined with bevacizumab and chemotherapy

Group Type EXPERIMENTAL

Toripalimab

Intervention Type DRUG

Neoadjuvant therapy: Toripalimab is given by intravenous infusion at 3mg/kg d1 every 2 weeks for 3 cycles.

Adjuvant therapy: Toripalimab is given by intravenous infusion at a dose of 240mg every 3 weeks for up to 9 cycles.

Bevacizumab

Intervention Type DRUG

Neoadjuvant therapy: Bevacizumab is given by intravenous infusion at 5mg/kg d1 every 2 weeks for 3 cycles.

Irinotecan

Intervention Type DRUG

Neoadjuvant therapy: Irinotecan is given by intravenous infusion at 180mg/m2 d1 every 2 weeks for 2 cycles.

Interventions

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Toripalimab

Neoadjuvant therapy: Toripalimab is given by intravenous infusion at 3mg/kg d1 every 2 weeks for 3 cycles.

Adjuvant therapy: Toripalimab is given by intravenous infusion at a dose of 240mg every 3 weeks for up to 9 cycles.

Intervention Type DRUG

Bevacizumab

Neoadjuvant therapy: Bevacizumab is given by intravenous infusion at 5mg/kg d1 every 2 weeks for 3 cycles.

Intervention Type DRUG

Irinotecan

Neoadjuvant therapy: Irinotecan is given by intravenous infusion at 180mg/m2 d1 every 2 weeks for 2 cycles.

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

1. Histologically confirmed colorectal adenocarcinoma meeting any of the following criterion: a) T3-4 resectable rectal cancer; b) T1-2 rectal cancer located within 12 cm from the anal verge and refusing direct surgery or radiation therapy; c) T4a-b resectable colon cancer.
2. Microsatellite instability-high (MSI-H) or DNA mismatch repair-deficient (dMMR).
3. Measurable disease according to the Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 criteria and haven't received any local treatment.
4. Eastern Cooperative Oncology Group (ECOG) 0-1.
5. Fully aware of this study and having signed informed consent.
6. Age 18 to 75 years old without gender limitation.
7. Good compliance.
8. Absolute neutrophil count ≥1500/mm3, platelet ≥100,000/mm3, Hb ≥10g/dl, serum creatinine ≤1.5 times ULN, creatinine clearance rate ≥50mL/min, ALT and AST ≤2.5 times ULN, INR or aPTT ≤1.5 times ULN (INR ≤2 times ULN and aPTT in normal range for patients who are on prophylactic anticoagulant therapy within 14 days before study treatment), total bilirubin level ≤2 times ULN (within 7 days before study treatment).
9. Women of childbearing age should confirm that serum pregnancy test is negative and agree to use effective contraceptive methods during study treatment and the following 60 days.

Exclusion Criteria

1. Previously received anti-PD1 or anti-PDL1 or anti-PDL2 or anti-CTLA4.
2. Uncontrolled active bleeding from the primary tumor or intestinal obstruction.
3. Contraindications of bevacizumab or irinotecan.
4. Hypersensitivity to other monoclonal antibodies.
5. Any active, known or suspected autoimmune disease.
6. Uncontrolled pleural effusion, pericardial effusion, or ascites to a moderate or greater extent.
7. History of one of the following dieases: idiopathic pulmonary fibrosis, organized pneumonia (eg. bronchiolitis obliterans), drug-induced pneumonia, idiopathic pneumonia and interstitial pneumonia, or evidence of active pneumonia through enhanced chest CT screening.
8. Major surgery within 4 weeks before enrollment and haven't fully recovered from the previous surgery.
9. Active bleeding or abnormal coagulation (aPTT \>43s or INR \>1.5 times ULN), or having a tendency to bleed or receiving thrombolytic or anticoagulant therapy.
10. Previously received allogeneic stem cell or parenchymal organ transplantation.
11. Any significant clinical or laboratory abnormality that the investigator considers to influence the safety assessment, eg. uncontrolled active infection, uncontrolled diabetes, hypertension that cannot be reduced to normal range with monotherapy, grade II or above peripheral neuropathy, congestive heart failure, heart disease (class II or higher) as defined by the New York College of Cardiology, myocardial infarction within 3 months prior to enrollment, unstable arrhythmias, unstable angina pectinis, chronic kidney disease, abnormal thyroid function and previous or co-existing malignancies.
12. History of uncorrected serum electrolyte disturbances such as potassium, calcium and magnesium.
13. HIV infection.
14. Active hepatitis B or hepatitis C.
15. Pregnancy or lactation period, or unwilling to use contraception during the trial.
16. With other malignancy within 5 year, except cervical carcinoma in situ, basal or squamous skin cancer, local prostatic carcinoma and ductal carcinoma in situ.
17. Use corticosteroids (dose of prednisone or similar drugs\> 10mg/day) or other immunosuppressive agents within 14 days before enrollment.
18. Patients with active tuberculosis (TB) who are receiving anti-TB treatment or have received anti-TB treatment within 1 year.
19. Active infection, or treatment with oral or intravenous antibiotics within the first 2 weeks prior to neoadjuvant therapy, except prophylactic administration.
20. Anti-infective vaccine (eg. influenza vaccine, varicella vaccine, etc.) injection within 4 weeks before neoadjuvant therapy.
21. Previous participation in other clinical trials within 4 weeks before neoadjuvant therapy.
22. Any other disease, metabolic disorder, abnormal physical examination or abnormal laboratory results that may contrainn the use of trial drug, or affect the reliability of study results, or lead to high risk of treatment complications, or affect patient compliance.
Minimum Eligible Age

18 Years

Maximum Eligible Age

75 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Peking University

OTHER

Sponsor Role lead

Responsible Party

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Shen Lin

Professor

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Lin Shen, Professor

Role: PRINCIPAL_INVESTIGATOR

Peking University Cancer Hospital & Institute

Locations

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Peking University Cancer Hospital and Institute

Beijing, Beijing Municipality, China

Site Status RECRUITING

Countries

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China

Central Contacts

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Lin Shen, Professor

Role: CONTACT

86-10-88196561

Jian Li, Professor

Role: CONTACT

86-10-88196561

Facility Contacts

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Lin Shen, Professor

Role: primary

86-10-88196561

Jian Li, Professor

Role: backup

86-10-88196561

References

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Wang Z, Wang X, Zhang X, Leng J, Cui M, Zhang J, Wang Q, Sun Y, Xu T, Chen M, Li J, Shen L. Toripalimab, bevacizumab, and irinotecan in dMMR/MSI locally advanced colorectal cancer: First-stage results from a phase 1b/2 trial. Cell Rep Med. 2025 Sep 16;6(9):102296. doi: 10.1016/j.xcrm.2025.102296. Epub 2025 Aug 15.

Reference Type DERIVED
PMID: 40818457 (View on PubMed)

Other Identifiers

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JS001-ISS-115

Identifier Type: -

Identifier Source: org_study_id

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