Toripalimab Plus Bevacizumab and Chemotherapy as Neoadjuvant Therapy in Advanced MSI-H or dMMR Colorectal Cancer
The Efficacy and Safety of Toripalimab Combined With Bevacizumab and Chemotherapy as Neoadjuvant Therapy in Patients With Advanced MSI-H or dMMR Colorectal Cancer: an Open-label, Multicenter, Single-arm, Phase Ib/II Study
1 other identifier
interventional
44
1 country
1
Brief Summary
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_1
Started Dec 2020
Typical duration for phase_1
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
Study Start
First participant enrolled
December 24, 2020
CompletedFirst Submitted
Initial submission to the registry
July 31, 2021
CompletedFirst Posted
Study publicly available on registry
August 3, 2021
CompletedPrimary Completion
Last participant's last visit for primary outcome
June 24, 2023
CompletedStudy Completion
Last participant's last visit for all outcomes
December 24, 2023
CompletedAugust 3, 2021
July 1, 2021
2.5 years
July 31, 2021
July 31, 2021
Conditions
Outcome Measures
Primary Outcomes (1)
Pathological complete response rate based on blinded, independent, central review
Percentage of patients who achieve pathological complete response (pCR) based on blinded, independent, central review (BICR).
10 weeks
Secondary Outcomes (12)
R0 recession rate
10 weeks
Time to surgery
10 weeks
Pathological complete response rate assessed by local investigator
10 weeks
Pathological complete response rate based on blinded, independent, central review (BICR) and the assessment of local investigator
10 weeks
Tumor regression grade (TRG)
10 weeks
- +7 more secondary outcomes
Study Arms (1)
Toripalimab combined with bevacizumab and chemotherapy
EXPERIMENTALInterventions
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.
Neoadjuvant therapy: Bevacizumab is given by intravenous infusion at 5mg/kg d1 every 2 weeks for 3 cycles.
Neoadjuvant therapy: Irinotecan is given by intravenous infusion at 180mg/m2 d1 every 2 weeks for 2 cycles.
Eligibility Criteria
You may qualify if:
- 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.
- Microsatellite instability-high (MSI-H) or DNA mismatch repair-deficient (dMMR).
- Measurable disease according to the Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 criteria and haven't received any local treatment.
- Eastern Cooperative Oncology Group (ECOG) 0-1.
- Fully aware of this study and having signed informed consent.
- Age 18 to 75 years old without gender limitation.
- Good compliance.
- 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).
- 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.
You may not qualify if:
- Previously received anti-PD1 or anti-PDL1 or anti-PDL2 or anti-CTLA4.
- Uncontrolled active bleeding from the primary tumor or intestinal obstruction.
- Contraindications of bevacizumab or irinotecan.
- Hypersensitivity to other monoclonal antibodies.
- Any active, known or suspected autoimmune disease.
- Uncontrolled pleural effusion, pericardial effusion, or ascites to a moderate or greater extent.
- 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.
- Major surgery within 4 weeks before enrollment and haven't fully recovered from the previous surgery.
- 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.
- Previously received allogeneic stem cell or parenchymal organ transplantation.
- 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.
- History of uncorrected serum electrolyte disturbances such as potassium, calcium and magnesium.
- HIV infection.
- Active hepatitis B or hepatitis C.
- Pregnancy or lactation period, or unwilling to use contraception during the trial.
- +7 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (1)
Peking University Cancer Hospital and Institute
Beijing, Beijing Municipality, 100142, China
Related Publications (1)
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.
PMID: 40818457DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Lin Shen, Professor
Peking University Cancer Hospital & Institute
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- OTHER
- Responsible Party
- PRINCIPAL INVESTIGATOR
- PI Title
- Professor
Study Record Dates
First Submitted
July 31, 2021
First Posted
August 3, 2021
Study Start
December 24, 2020
Primary Completion
June 24, 2023
Study Completion
December 24, 2023
Last Updated
August 3, 2021
Record last verified: 2021-07