Observation and evaluation of the safety and efficacy of PD-1 antibody combined with IBI310 and neoadjuvant chemotherapy in the treatment of locally advanced rectal cancer
Primary objectives:
Pathological complete response (pCR) rate;
Secondary objectives:
Treatment-related adverse events (CTCAE 5.0), clinical complete response (cCR) rate, major pathological response (MPR) rate, R0 resection rate, sphincter preservation rate, surgical complications, 3-year disease-free survival (DFS), and overall survival (OS);
Inclusion Criteria:
1) Sign written informed consent before implementing any trial related processes;
2) Male or female, age ≥ 18 years;
3) ECOG score 0-1;
4) The primary lesion is a locally advanced rectal adenocarcinoma with histopathologically confirmed MSI-H/dMMR characteristics.;
5) Combined with endoscopic ultrasonography / rectal MR scan diagnosis, patients with clinical stage t2-4a or n+m0 were evaluated for lesion resectability;
6) According to the response evaluation criteria for solid tumors (RECIST version 1.1), there was at least one measurable lesion on imaging;
7) The patient has not received any anti-tumor treatment in the past, including but not limited to surgery, radiotherapy, chemotherapy, immunotherapy, targeted therapy Therapeutics et al;
8) Sufficient organ function, subjects need to meet the following laboratory indicators:
9) Female subjects of childbearing age should receive a urine or serum pregnancy test with negative results within 3 days before receiving the first study drug administration (day 1 of cycle 1). If the urine pregnancy test result cannot be confirmed as negative, a blood pregnancy test is required. Women of non reproductive age were defined as having been postmenopausal for at least 1 year, or having undergone surgical sterilization or hysterectomy;
10) If there is a risk of conception, all subjects (whether male or female) need to use contraceptive measures with an annual failure rate of less than 1% during the whole treatment period until 120 days after the last dose of study drug (or 180 days after the last dose of chemotherapy drug).
Exclusion Criteria:
Note: hepatitis B patients who meet the following criteria can also be included in the group:
Prior to the first administration, if the HBV viral load is less than 1000 copies/ml (200 IU/ml), subjects should receive anti HBV treatment throughout the entire study chemotherapy period to avoid viral reactivation;
For subjects with anti HBc (+), HBsAg (-), anti HBs (-), and HBV viral load (-), prophylactic anti HBV treatment is not necessary, but close monitoring of viral reactivation is required;
Active HCV infected subjects (HCV antibody positive and HCV-RNA level above the detection limit);
a) Resting electrocardiogram shows significant and difficult to control abnormalities in rhythm, conduction, or morphology, such as complete left bundle branch block, grade II or higher heart block, ventricular arrhythmia, or atrial fibrillation; b) Unstable angina pectoris, congestive heart failure, chronic heart failure classified as NYHA ≥ 2; c) Myocardial infarction occurred within 6 months prior to randomization; d) Poor blood pressure control (systolic blood pressure>140 mmHg, diastolic blood pressure>90 mmHg); e) A history of non infectious pneumonia requiring corticosteroid treatment within the year prior to the first administration, or current clinical active interstitial lung disease; f) Active pulmonary tuberculosis; g) There are active or uncontrolled infections that require systemic treatment; h) There is clinical active diverticulitis, abdominal abscess, and gastrointestinal obstruction; i) Liver diseases such as cirrhosis, decompensated liver disease, acute or chronic active hepatitis; j) Poor control of diabetes (FBG>10mmol/L); k) Urine routine shows urinary protein ≥++and confirms 24-hour urinary protein quantification>1.0 g; l) Patients with mental disorders who are unable to cooperate with treatment;
PD-1:200mg IV, D1, Q3W IBI310:1.0mg/kg IV, D1,Q3W Capecitabine: 1000 mg/m2, Po, bid, d1-d14, q3w Oxaliplatin: 130 mg/m2, IV, D1, q3w
Xi'an, Shaanxi 710032, China
liushushang8@126.com+86 15721985836
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