Colorectal Cancer
Conditions
Interventions
Experimental group:Iparomlimab and Tuvonralimab combined with fruquintinib
Sponsors
Shanghai East Hospital
Eligibility
Sex/Gender
All
Age
18 Years to 85 Years
Inclusion criteria
Inclusion criteria: 1. Male or female, age >= 18 years. 2. Histologically or cytologically confirmed unresectable, locally advanced or metastatic colorectal cancer. 3. Tumor tissue confirmed as dMMR by immunohistochemistry (IHC) or as MSI-H by PCR or NGS. 4. Subjects must have received first-line immune checkpoint inhibitor therapy (anti-PD-1 monoclonal antibody, anti-PD-L1 monoclonal antibody) and experienced disease progression after prior ICI treatment (patients with primary resistance may be enrolled). 5. At least one measurable lesion according to RECIST 1.1. 6. ECOG Performance Status score: 0-1. 7. Estimated life expectancy of greater than 3 months. 8. Normal function of major organs, and laboratory tests meeting the following criteria: (1) Hemoglobin (Hb) >= 9 g/dL; Absolute Neutrophil Count (ANC) >= 1.5 × 10?/L; Platelets (PLT) >= 75 × 10?/L; White Blood Cell count (WBC) >= 3.0 × 10?/L; (2) Creatinine Clearance (CLcr) calculated by the Cockcroft-Gault equation >= 45 mL/min; (3) Total Bilirubin (TBIL) = 50%; (5) International Normalized Ratio (INR) <= 1.5 × ULN, Activated Partial Thromboplastin Time (APTT) <= 1.5 × ULN. 9. Prior to the first dose, any adverse events related to previous anti-tumor therapy have recovered (i.e., <= Grade 1, according to CTCAE v5.0), excluding alopecia (any grade) and peripheral sensory neuropathy, hypomagnesemia, or lymphopenia of Grade <= 2, as well as other abnormalities that, in the assessment of the investigator and/or sponsor, the benefit of treatment for the subject outweighs the risk. 10. Subjects agree to use effective contraception from the time of signing the informed consent form until 180 days after the last dose. Women of childbearing potential cannot be pregnant or breastfeeding. 11. Subjects must voluntarily join this study, sign the informed consent form, have good compliance, and cooperate with follow-up.
Exclusion criteria
Exclusion criteria: 1. Previous treatment with anti-CTLA-4 antibodies, immune checkpoint agonist antibodies (e.g., anti-ICOS, CD40, CD137, GITR, OX40 antibodies, etc.), or cell-based immunotherapy. 2. Previous treatment with small molecule TKI therapies, such as regorafenib. 3. Known history of hypersensitivity to macromolecular protein preparations. Contraindications or hypersensitivity to any component of Apatolimab or Fruquintinib. 4. Therapeutic use of full-dose oral or injectable anticoagulants or thrombolytic agents within 10 days prior to the initiation of study treatment (prophylactic use of low-dose aspirin, low molecular weight heparin, and rivaroxaban is permitted). 5. Requirement for systemic corticosteroid therapy (>10 mg daily prednisone equivalent) or other immunosuppressive drugs (e.g., cyclophosphamide, azathioprine, methotrexate, thalidomide, TNF-a inhibitors, etc.) within 2 weeks prior to the first dose. Topical corticosteroids, nasal sprays, and inhaled steroids are permitted. Prophylactic use of systemic corticosteroids for contrast media allergy is permitted. 6. Active or potentially recurrent autoimmune diseases, with the following exceptions: vitiligo, alopecia, psoriasis, or eczema not requiring systemic therapy; hypothyroidism due to autoimmune thyroiditis requiring only stable hormone replacement therapy; type I diabetes mellitus requiring only stable insulin replacement therapy. 7. History of gastrointestinal perforation and/or fistula, or history of intestinal obstruction within 6 months prior to the first dose (subjects with initial symptoms/signs of incomplete/complete obstruction may be enrolled if symptoms resolved after treatment and the investigator deems them eligible), extensive intestinal resection (partial colectomy or extensive small bowel resection with chronic diarrhea), Crohn's disease, ulcerative colitis, or chronic long-term diarrhea. 8. Symptomatic, untreated, or not clinically stable brain metastases or leptomeningeal disease. 9. History of interstitial lung disease and/or pneumonitis, or pulmonary hypertension. 10. Poorly controlled hypertension (systolic BP >150 mmHg and/or diastolic BP >100 mmHg) despite standard treatment, poorly controlled diabetes mellitus, or uncontrolled or symptomatic cardiac arrhythmia. 11. Thromboembolic events within 6 months prior to the initiation of study treatment, such as cerebrovascular accident (including transient ischemic attack, cerebral hemorrhage, cerebral infarction), pulmonary embolism, etc. 12. Myocardial infarction within the past 12 months, severe/unstable angina, or symptomatic congestive heart failure (NYHA Class III or IV). 13. Drainage of ascites, pleural effusion, or pericardial effusion within 4 weeks prior to enrollment. 14. Severe, non-healing, or dehisced wounds, active ulcers, or untreated fractures. 15. Other concurrent active malignancies, except for malignancies disease-free for over 5 years or appropriately treated and considered cured carcinoma in situ. 16. Known active HIV, HBV, or HCV infection. 17. Major surgery (excluding needle biopsy) within 4 weeks prior to the first dose without full recovery. 18. Any other condition deemed by the investigator to make the subject unsuitable for participation in this study.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Objective response rate, ORR; | — |
Secondary
| Measure | Time frame |
|---|---|
| Progression-Free Survival, PFS;Disease Control Rate, DCR;Overall Survival, OS;Adverse Event, AE; | — |
Countries
China
Contacts
Public ContactJingde Chen
Shanghai East Hospital
Outcome results
None listed