Colorectal cancer
Conditions
Interventions
FOLFIRI + Bevacizumab group:FOLFIRI + Bevacizumab
SHR-A1811 + Bevacizumab group:SHR-A1811 + Bevacizumab
Sponsors
Peking Union Medical College Hospital
Eligibility
Sex/Gender
All
Age
18 Years to 75 Years
Inclusion criteria
Inclusion criteria: 1. Provide written informed consent and voluntarily participate in this study; 2. Male or female aged 18-75 years; 3. Patients with histologically or cytologically confirmed unresectable recurrent or metastatic colorectal adenocarcinoma; 4. Patients who have previously received first-line standard treatment containing oxaliplatin combined with fluoropyrimidine and have experienced disease progression (patients whose disease has progressed within 12 months after completing neoadjuvant or adjuvant therapy can be included patients previously treated with first-line irinotecan can be included if, after discussion with the lead site investigator, it is determined that the patient may benefit from the control group); 5. HER2 expression: including HER2 high expression patients (IHC 3+ / IHC 2+ with FISH positive) or HER2 low-to-moderate expression patients (IHC 2+ with FISH negative or IHC 1+), referencing gastric cancer criteria; 6. ECOG (Eastern Cooperative Oncology Group) performance status score of 0-1; 7. Able to provide RAS/BRAF gene status report; 8. Expected survival of at least 6 months; 9. Investigator-assessed measurable baseline lesions (per RECIST 1.1) measurable lesions must not have received local treatments such as radiotherapy (lesions within prior radiotherapy areas can be selected as target lesions if progression is confirmed); 10. Major organ function must meet the following requirements (no use of blood products or growth factor corrective treatments within 14 days prior to the first dose of study drug): absolute neutrophil count (ANC) >=1.5 × 10^9/L platelets >=100 × 10^9/L hemoglobin >=90 g/L serum albumin >=30 g/L total bilirubin 60 mL/min (Cockcroft-Gault formula) activated partial thromboplastin time (APTT) and international normalized ratio (INR) <=1.5 × ULN (patients on stable anticoagulant therapy, such as low molecular weight heparin or warfarin with INR within the therapeutic range, may be screened); 11. Women of childbearing potential must have a negative blood pregnancy test within 3 days prior to first dosing and must not be breastfeeding. They must agree to use effective contraception during the trial and for at least 7 months after the last dose of SHR-A1811 or for at least 6 months after the last dose of other investigational drugs. Male subjects with partners of childbearing potential must be surgically sterilized or agree to use effective contraception during the trial and for at least 7 months after the last dose of SHR-A1811 or for at least 6 months after the last dose of other investigational drugs, sperm donation is not allowed during the trial.
Exclusion criteria
Exclusion criteria: 1.Previous anti-tumor therapy toxicity has not recovered to CTCAE v5.0 grade evaluation = grade 1 (except for toxicities judged by the investigator to have no safety risk, such as alopecia, etc.) or the level specified in the enrollment/exclusion criteria; 2.Known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Subjects who have received prior treatment for brain metastases may participate in treatment provided they have stable brain metastases and have not been treated with steroids for brain metastases for at least 28 days prior to study entry. This exception does not include carcinomatous meningitis, as patients with carcinomatous meningitis are excluded regardless of clinical stability; 3.Known genetic assay of MSI-H or immunohistochemistry assay of dMMR; 4.Previous allergy to monoclonal antibodies, preparation components of SHR-A1811 products and anti-angiogenic drugs; 5.Patients who have received HER-2 ADC therapy in the past; 6.Major surgery, open biopsy or severe trauma 28 days before the first dose; 7.Patients with any severe and/or uncontrolled diseases, including: patients with unsatisfactory blood pressure control Suffering from grade I or above myocardial ischemia or myocardial infarction, arrhythmia (including QT interval =480ms) and grade I cardiac insufficiency Active or uncontrolled serious infection Liver disease such as decompensated liver disease, active hepatitis B (HBV-DNA=104 copy number/ml or 2000IU/ml) or hepatitis C (positive hepatitis C antibody and HCV-RNA above the lower limit of detection of the analytical method) Those whose urine routine showed a = of urine protein and confirmed that the 24-hour urine protein quantitative > was 1.0g; 8.Significant clinically significant bleeding symptoms or clear bleeding tendency within 3 months before the first dose, such as gastrointestinal bleeding, hemorrhagic gastric ulcer, or vasculitis; 9.Arterial/venous thrombotic events that occurred within 6 months before the first dose, such as cerebrovascular accident (including transient ischemic attack, cerebral hemorrhage, cerebral infarction), deep vein thrombosis and pulmonary embolism, etc., can be enrolled after being judged by the investigator; 10.Has another malignancy that is progressing or requires active treatment, except for non-melanomatous skin cancer and cervical cancer in situ that have been potentially treated; 11.According to the investigator's judgment, the subject has other factors that may cause him to be forced to terminate the study midway, such as suffering from other serious diseases (including mental illness) requiring combined treatment, serious abnormalities in laboratory examination values, family or social factors, which may affect the safety of the subject or the collection of trial data.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Objective Response Rate; | — |
Secondary
| Measure | Time frame |
|---|---|
| Safety;Disease Control Rate;Overall Survival;Progression Free Survival; | — |
Countries
China
Contacts
Public ContactXicheng Wang
Peking Union Medical College Hospital
Outcome results
None listed