A Clinical Study of BioTTT001 in Combination With Toripalimab and Regorafenib in Patients With Colorectal Cancer

Exclusion Criteria

• •1. Known allergy to the investigational drug or its components;
• •2. Previous treatment with other adenovirus drugs;
• •3. Patients with active autoimmune diseases (such as systemic lupus erythematosus, rheumatoid arthritis, etc.), except type 1 diabetes, hypothyroidism that only needs hormone replacement therapy, and skin diseases that do not need systemic treatment (such as vitiligo, psoriasis or alopecia);
• •4. Received treatment with nitrosourea or mitomycin C within 6 weeks before the first dose of BioTTT001; received oral fluorouracil and small molecule targeted drug therapy within 2 weeks or 5 half-lives of the drug within 2 weeks before the first dose of BioTTT001; received traditional Chinese medicine therapy with anti-tumor indications within 2 weeks before the first dose of BioTTT001; received chemotherapy, radiotherapy, biological therapy other than the drugs mentioned above within 28 days before the first dose of BioTTT001；
• •5. Patients who have not recovered from the adverse reactions of previous treatments (the treatment-related toxicity ≤ grade 2, except for alopecia, pigmentation or other tolerable events judged by the investigator ).
• •6. History of other malignancies (except cured basal cell skin cancer, cervical carcinoma in situ, Papillary carcinoma of thyroid gland, low-risk GIST etc.) within 5 years before study drug administration;
• •7. Patients who have undergone any major surgery (except needle biopsy, etc.) or severe trauma within 4 weeks before the first dose of BioTTT001;
• •8. Patients who have been treated with high-dose systemic corticosteroids (prednisone \> 10 mg/day or equivalent doses) or other immunosuppressants within 2 weeks before the first dose of BioTTT001;
• •9. NYHA≥grade 3; LVEF\<50%; male QTc\>450 mms, female QTc\>470 mms;
• •10. Patients with active tuberculosis or drug-induced interstitial lung disease；
• •11. Patients with active infection requiring systemic anti-infective therapy;
• •12. In a state of immunosuppression, such as severe combined immunodeficiency disease or concurrent opportunistic infections;
• •13. HBsAg positive, and blood HBV DNA≥100 IU/mL; anti-HCV positive; HIV positive; active syphilis;
• •14. Patients with pleural effusion and ascites with clinical symptoms that require repeated drainage;
• •15. Patients with central nervous system metastases or meningeal metastases with clinical symptoms;
• •16. Patients with contraindications to hepatic arterial perfusion therapy;
• •17. Pregnant or lactating women;
• •18. Patients with prior organ transplants;
• •19. Other reasons judged by the investigator.