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Sintilimab (R&D code: IBI308) is a recombinant human-derived IgG4 type PD-1 monoclonal antibody. PD-1 inhibitor combined with chemotherapy has synergistic effect to further enhance anti-tumor immunity. This study is a phase III clinical study of a three-week regimen of sintilimab combined with the XELOX+ bevacizumab for RAS-mutant metastatic colorectal cancer patients who had not received any treatment before. The purpose of this study is to explore the efficacy of sintilimab combined with XELOX + bevacizumab as first line therapy.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Sintilimab + XELOX + Bevacizumab | Experimental | Sintilimab + XELOX + Bevacizumab |
|
| XELOX + Bevacizumab | Active Comparator | XELOX + Bevacizumab |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Sintilimab | Drug | Sintilimab Injection: 200 mg, i.v., D1, Q3W |
| |
| Measure | Description | Time Frame |
|---|---|---|
| Progression free survival time | Progression-free survival is defined as the time from randomization to the first documented disease progression according to RECIST version 1.1, or to death from any cause, whichever occurred first. | From randomization to the first documented disease progression, or to death from any cause, up to 2 years |
| Measure | Description | Time Frame |
|---|---|---|
| Objective Response Rate | According to RECIST 1.1 criteria, the proportion of patients whose tumor efficacy was evaluated as CR and PR among all evaluable patients | From randomization to disease progression |
| Overall survival time |
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Inclusion Criteria:
Exclusion Criteria:
Active autoimmune disease requiring systemic treatment occurred in the previous 2 years.
Diagnosed as immunodeficiency or experimental treatment is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose. After consultation with the sponsor, the use of a physiological dose of corticosteroids may be approved.
Adverse events caused by anti-tumor monoclonal antibodies (mAbs) within 4 weeks prior to study day 1 or drugs received 4 weeks prior to the study have not recovered.
Adverse events caused by chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study day 1, or previously received drugs, have not recovered (ie, ≤1 or reached baseline levels).
Other malignancies that are progressing or require active treatment are known. Except for basal cell carcinoma, cutaneous squamous cell carcinoma, or cervical carcinoma in situ that have undergone radical treatment.
Active central nervous system (CNS) metastasis and/or cancerous meningitis are known to exist.
There are active infections that require systemic treatment.
It is possible to confuse the test results, the medical history or disease evidence, the treatment or laboratory value abnormalities that hinder the subject's full participation in the study, or the investigator believes that participating in the study is not in the best interests of the subject.
There are known mental or substance abuse disorders that may have an impact on compliance with test requirements.
Female subjects who are pregnant or lactating, or who are expected to be pregnant during the planned trial period (from 120 days after screening visits to 120 days after the last dose of study treatment, or 180 days after the last dose of study treatment), or Male subjects whose spouse is pregnant.
A history of infection with human immunodeficiency virus (HIV) (HIV 1/2 antibody) is known.
Active hepatitis B or C.
Live vaccines were vaccinated within 30 days of the start date of the study treatment plan.
RAS wild type
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| Name | Affiliation | Role |
|---|---|---|
| Ying Yuan | 2nd Affiliated Hospital, School of Medicine, Zhejiang University, China | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Xuefeng Fang | Hangzhou | Zhejiang | 310009 | China |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 37464378 | Derived | Fang X, Zhong C, Weng S, Hu H, Wang J, Xiao Q, Wang J, Sun L, Xu D, Liao X, Dong C, Zhang S, Li J, Ding K, Yuan Y. Sintilimab plus bevacizumab and CapeOx (BBCAPX) on first-line treatment in patients with RAS mutant, microsatellite stable, metastatic colorectal cancer: study protocol of a randomized, open-label, multicentric study. BMC Cancer. 2023 Jul 18;23(1):676. doi: 10.1186/s12885-023-11139-z. |
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| Bevacizumab |
| Drug |
intravenous bevacizumab (7.5 mg/kg, day 1) in each 21-day cycle |
|
| Oxaliplatin | Drug | intravenous oxaliplatin (130 mg/m2, day 1) in each 21-day cycle |
|
| Capecitabine | Drug | oral capecitabine (1 g/m2, days 1-14) in each 21-day cycle |
|
Time from randomization to death from any cause
| From randomization to death from any cause, up to 3 years |
| Disease control rate | According to RECIST 1.1 criteria, the proportion of subjects whose tumor efficacy was evaluated as CR, PR and SD among all evaluable patients | From randomization to disease progression |
| Clinical benefit rate | The proportion of patients who achieved CR PR or maintained SD for a certain period of time (6 months) | From randomization to disease progression |
| Adverse Events | Incidence of AEs (all grades), incidence of grade 1-2 AEs, incidence of grade 3-4 AEs, incidence of grade 5 AEs, treatment discontinuation rate, discontinuation rate due to adverse reactions, all subjects who used at least one study drug were included | From randomization to 28 days after disease progression |
| ID | Term |
|---|---|
| D015179 | Colorectal Neoplasms |
| ID | Term |
|---|---|
| D007414 | Intestinal Neoplasms |
| D005770 | Gastrointestinal Neoplasms |
| D004067 | Digestive System Neoplasms |
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D004066 | Digestive System Diseases |
| D005767 | Gastrointestinal Diseases |
| D003108 | Colonic Diseases |
| D007410 | Intestinal Diseases |
| D012002 | Rectal Diseases |
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| ID | Term |
|---|---|
| C000632826 | sintilimab |
| D000068258 | Bevacizumab |
| D000077150 | Oxaliplatin |
| D000069287 | Capecitabine |
| ID | Term |
|---|---|
| D061067 | Antibodies, Monoclonal, Humanized |
| D000911 | Antibodies, Monoclonal |
| D000906 | Antibodies |
| D007136 | Immunoglobulins |
| D007162 | Immunoproteins |
| D001798 | Blood Proteins |
| D011506 | Proteins |
| D000602 | Amino Acids, Peptides, and Proteins |
| D012712 | Serum Globulins |
| D005916 | Globulins |
| D056831 | Coordination Complexes |
| D009930 | Organic Chemicals |
| D003841 | Deoxycytidine |
| D003562 | Cytidine |
| D011741 | Pyrimidine Nucleosides |
| D011743 | Pyrimidines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D005472 | Fluorouracil |
| D014498 | Uracil |
| D011744 | Pyrimidinones |
| D003853 | Deoxyribonucleosides |
| D009705 | Nucleosides |
| D009706 | Nucleic Acids, Nucleotides, and Nucleosides |
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