Colorectal cancer
Conditions
Interventions
Experimental Group: QL1706:5 mg/kg IV ,d1,q3wks
Tas-102:30 mg/m2,po,bid ,d1-5,q2wks
Bevacizumab:5 mg/kg, IV ,d1,q3wks
Sponsors
The First Affiliated Hospital of University of Science and Technology of China
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Inclusion criteria
Inclusion criteria: 1. The age is over 18 years old, regardless of gender; 2. Metastatic colorectal cancer confirmed by histopathological examination; 3. Failure of frontline irinotecan and oxaliplatin: (1) Treatment failure was defined as the occurrence of intolerable toxicity or disease progression during the treatment or tumor recurrence or metastasis after the end of treatment. (2) one or more chemotherapy drugs with a treatment duration of >=1 cycle or more per line of treatment; Early adjuvant/neoadjuvant therapy was allowed. If tumor recurrence or metastasis occurred during or within 24 weeks after completion of adjuvant/neoadjuvant therapy, the previous adjuvant/neoadjuvant therapy was considered as systemic chemotherapy. (3) Targeted drugs, immunosuppressants or radiotherapy were allowed as prior treatments; (4) Chemotherapy combined with targeted drugs was allowed as the initial treatment. 4. At least one measurable lesion (according to RecIS criteria, version 1.1); 5. Expected survival time >=12 weeks; 6.ECOG performance status 0-2; 7.RAS status is known; 8. During the screening period, the patient had good organ function: (1) Hematology (no blood transfusion and no treatment with blood components or granulocyte colony-stimulating cytokines within 14 days) : neutrophil count (NEU) >=1.5×10^9/L (1500 /mm3); Platelet (PLT) count >=100×10^9/L (100,000/mm3); Hemoglobin >=90 g/L; (2) Liver: serum total bilirubin (TBil) = 30 mL/min; (4) Coagulation function: international normalized ratio (INR) <=1.5, prothrombin time (PT) or activated partial thromboplastin time (APTT) <=1.5×ULN; (5) International normalized ratio (INR) <=1.5; Activated partial thromboplastin time (APTT) <=1.5×ULN; 9. Patients or their family members can understand the study protocol and are willing to participate in the study, and sign the written informed consent; 10. Patients deemed to benefit by the investigator
Exclusion criteria
Exclusion criteria: 1. Factors significantly affecting oral drug absorption, such as inability to swallow, chronic diarrhea, and intestinal obstruction. 2. Known hypersensitivity to any component of the investigational drugs or their excipients. 3. Uncontrolled hypertension (systolic blood pressure >150 mmHg or diastolic blood pressure >90 mmHg despite optimal medical management), history of hypertensive crisis or hypertensive encephalopathy, or active bleeding, pulmonary hemorrhage, hemoptysis, or bloody ascites. 4. History of gastrointestinal perforation or gastrointestinal fistula within 6 months prior to the first dose. Patients may be enrolled if the perforation or fistula has been treated (e.g., surgically resected or repaired) and is considered by the investigator to have recovered or resolved. 5. History of Grade 4 venous thromboembolism (including pulmonary embolism). 6. Severe uncontrolled recurrent infections, including abdominal infections, or other severe uncontrolled concomitant illnesses (e.g., uncontrolled diabetes mellitus, cardiovascular diseases, or severe gastrointestinal disorders). 7. Major surgery =28 days before the first intervention. 8. Known history of psychoactive drug abuse or drug addiction. 9. Pregnant or breastfeeding women, or male patients unwilling to use effective contraception. 10. History of or concurrent other malignancies within 5 years, except for cured carcinoma in situ of the cervix, non-melanoma skin cancer, and superficial bladder tumors [Ta (non-invasive tumor), Tis (carcinoma in situ), and T1 (tumor invades lamina propria)]. 11. Active or previously documented inflammatory bowel disease (e.g., Crohn's disease or ulcerative colitis), malabsorption syndrome, or uncontrolled nausea, vomiting, diarrhea, or other severe gastrointestinal disorders that significantly compromise drug administration or absorption. 12. Prior treatment with a PD-1/CTLA-4 bispecific antibody. 13. Symptomatic central nervous system (CNS) metastases. Patients with previously treated brain metastases who are considered stable by the investigator may be eligible. 14. Active or suspected autoimmune diseases, including but not limited to systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, etc. Exceptions include: type I diabetes mellitus or hypothyroidism controlled with stable dose replacement therapy; skin diseases not requiring systemic treatment (e.g., psoriasis, vitiligo). 15. Systemic use of corticosteroids (prednisone >10 mg/day or equivalent) or other immunosuppressive medications within 14 days prior to the first study dose. 16. History of immunodeficiency, including other acquired or congenital immunodeficiency diseases, or history of organ transplant, allogeneic hematopoietic stem cell transplantation, or solid organ transplantation. 17. Administration of live vaccines within 4 weeks prior to the first study dose. 18. Positive human immunodeficiency virus (HIV) antibody test, active hepatitis B or hepatitis C. The following conditions are permitted: (1) Positive hepatitis B core antibody (HBcAb) or hepatitis B surface antigen (HBsAg) with HBV DNA below the lower limit of detection (negative) or <500 IU/mL at the investigating center, and considered by the investigator to have no evidence of active infection based on clinical management and presentation. (2) Positive hepatitis C antibody with HCV RNA below the lower limit of detection (negative) at the investigating center. 19. Deemed unsui
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Progression-free survival; | — |
Secondary
| Measure | Time frame |
|---|---|
| Overall survival period;Objective response rate;Disease control rate; | — |
Countries
China
Contacts
Public ContactXiaoDong Jiang
The First Affiliated Hospital of University of Science and Technology of China
Outcome results
None listed