Stage II or III colon adenocarcinoma, or stage II or III rectal adenocarcinoma with the distal margin located <10 cm from the anal verge.
Conditions
Interventions
Cohort D (Other KRAS Mutations or Wild-Type KRAS):Radiotherapy+chemotherapy+immunotherapy
Cohort A(dMMR?MSI-H):Immunotherapy
Cohort B2(KRAS G12C mutation):Radiotherapy+chemotherapy+targeted therapy
Cohort C1(KRAS G12D mutation):Radiotherapy+chemotherapy+immunotherapy
Cohort C2(KRAS G12D mutation):Radiotherapy+chemotherapy+targeted therapy
Cohort B1(KRAS G12C mutation):Radiotherapy+chemotherapy+immunotherapy
Sponsors
Fudan University Cancer Hospital
Eligibility
Sex/Gender
All
Age
18 Years to 75 Years
Inclusion criteria
Inclusion criteria: To be enrolled in the study, subjects had to meet all of the following eligibility criteria: 1. Age 18-75 years old, both male and female; 2. Histologically confirmed, untreated cT3-4/cN0-2 rectal adenocarcinoma with tumor lower pole less than 10cm from anal verge. Cohort A could include histologically confirmed, untreated stage II or III colon adenocarcinoma; Cohort A: dMMR/MSI-H detected by immunohistochemistry or NGS sequencing, regardless of CMS type and KRAS mutation status; Cohort B: KRAS G12C mutation detected by PCR or NGS sequencing; Cohort C: KRAS G12D mutation detected by PCR or NGS sequencing; Cohort D: PCR or NGS sequencing showed no KRAS G12C or G12D mutation, and CMS typing was confirmed by transcriptome sequencing. 4. At least one measurable lesion according to RECIST version 1.1 criteria; 5. Eastern Cooperative Oncology Group (ECOG) performance status score 0-1; 6. All screening laboratory tests were performed, as required by the protocol, within 7 days before enrollment. Laboratory values for screening must meet the following criteria: Blood routine (no blood transfusion, no G-CSF, no medication correction within 14 days before screening) : 1) Hb>=90 g/L; 2) ANC>=1.5×10^9/L; 3) platelet count >=100×10^9/L; Biochemical tests: 1) TBIL=50 mL/min (Cockcroft-Gault formula); Coagulation function: 1) International normalized ratio (INR) and activated partial thromboplastin time (APTT) =2+, 24-hour urinary protein quantification could be performed, and 24-hour urinary protein quantification <1.0g could be included); 7. Left ventricular ejection fraction (LVEF) =55%; 8. Women of childbearing age must have a negative blood/urine pregnancy test within 7 days before the first dose of medication. Female participants of childbearing age and male participants whose partner was a woman of childbearing age had to agree to use a highly effective method of contraception from the time they signed the informed consent form until 180 days after the last dose of study medication. 9. The subjects voluntarily participated in this study, signed the informed consent form, with good compliance, and cooperated with follow-up.
Exclusion criteria
Exclusion criteria: 1.Prior cytotoxic chemotherapy, immunotherapy, or radiotherapy for colorectal cancer; 2.Major surgery or significant trauma within 28 days prior to the first dose, or planned non-colorectal cancer surgery during the study period; 3.Diagnosis of any other malignancy within 5 years prior to the first dose, with the exception of early-stage tumors that have been cured by radical treatment, such as carcinoma in situ of the lung, non-melanoma skin cancer, basal cell or squamous cell skin cancer, or cervical carcinoma in situ, which may be considered for exclusion after assessment by the investigator; 4.Severe cardiovascular disease, such as New York Heart Association (NYHA) class >=2 heart failure, unstable angina, unstable arrhythmia, myocardial infarction or cerebrovascular accident occurring within 6 months prior to the first dose; carotid ultrasound showing stenosis =50% or presence of two or more high-risk plaque features (carotid ultrasound is required only for Cohort D); 5.Human immunodeficiency virus (HIV) infection or known acquired immunodeficiency syndrome (AIDS), active hepatitis B (HBV DNA >=1000 IU/ml), hepatitis C (positive hepatitis C antibody with HCV-RNA above the lower limit of detection of the assay), or co-infection with hepatitis B and hepatitis C; 6.Severe pulmonary disease at screening, such as pulmonary embolism, chronic obstructive pulmonary disease, interstitial lung disease, or baseline chest imaging findings suggestive of active pulmonary inflammation; signs and symptoms of infection requiring oral or intravenous antibiotic treatment within 2 weeks prior to the first dose of study drug, except for prophylactic antibiotic use; 7.Clinical or imaging evidence of intestinal obstruction or perforation; or assessed by the investigator as having a high risk of perforation or bleeding; 8.Subjects with active, known, or suspected autoimmune diseases or a history of organ transplantation; 9.Severe systemic infection or patients with other serious diseases; 10.Known history of psychotropic substance abuse or drug addiction; 11.Presence of other serious physical or mental illnesses or laboratory abnormalities that may increase the risk of participating in the study, or interfere with the study results, or patients deemed by the investigator to be unsuitable for participation in this study; 12.History of hypersensitivity to the study drug or its excipients.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Complete response rate; | — |
Secondary
| Measure | Time frame |
|---|---|
| Organ or anal preservation rate;3-year local recurrence-free survival;3y-DFS;3-year overall survival rate;Distant metastasis-free survival at 3 years;R0 resection rate; | — |
Countries
China
Contacts
Public ContactZhen Zhang, Sanjun Cai
Fudan University Cancer Hospital
Outcome results
None listed