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

Prior treatment

• Known allergy to the investigational drug or its components;
• Previous treatment with other adenovirus drugs;
• 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；
• 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 ).
• Patients who have undergone any major surgery (except needle biopsy, etc.) or severe trauma within 4 weeks before the first dose of BioTTT001;
• 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;
• In a state of immunosuppression, such as severe combined immunodeficiency disease or concurrent opportunistic infections;
• Patients with contraindications to hepatic arterial perfusion therapy;
• Patients with prior organ transplants;

Other illness

• 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);
• 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;
• Patients with active tuberculosis or drug-induced interstitial lung disease；
• Patients with active infection requiring systemic anti-infective therapy;
• HBsAg positive, and blood HBV DNA≥100 IU/mL; anti-HCV positive; HIV positive; active syphilis;

Lab values

• NYHA≥grade 3; LVEF\<50%; male QTc\>450 mms, female QTc\>470 mms;

Other

• Patients with pleural effusion and ascites with clinical symptoms that require repeated drainage;
• Patients with central nervous system metastases or meningeal metastases with clinical symptoms;
• Pregnant or lactating women;
• Other reasons judged by the investigator.

• Age range from 18 to 70 years old (including the threshold), no gender restrictions;
• Patients with a definitive histopathological or cytological diagnosis of colorectal cancer with hepatic metastases who have received and failed at least second-line standard therapy in the past, or who have been assessed by the investigator to be unsuitable for standard therapy;
• At least one measurable lesion according to the Response Evaluation Criteria in Solid Tumors (RECIST) 1.1;
• WBC≥3.0×10\^9/L; ANC≥1.5×10\^9/L (without cytokine therapy within one week before the screening ); Hb≥90g/L(without blood transfusion within one week before the screening);PLT≥90×10\^9/L(without Platelet transfusion or thrombopoietin (TPO) within one week before the screening)；ALT and AST≤5×ULN；Cr≤1.5×ULN or CCr\>50mL/min; TBIL≤1.5×ULN; APTT≤1.5×ULN and INR/PT≤1.5×ULN；
• ECOG 0\~2；
• Expected survival ≥ 3 months;
• Consent to contraception；
• Understand and voluntarily sign a written ICF and be willing to comply with all trial requirements.