Safety and Efficacy of Intravenous IDOV-SAFETM in Patients With Advanced Solid Tumors

Inclusion Criteria:

• Understand and voluntarily sign a written informed consent;

• Male and female, ≥18 years old and ≤75 years old;

• Histologically or cytologically confirmed advanced malignant solid tumors that donot respond to standard treatment (disease progression or treatment intoleranceafter treatment) or currently lack effective standard treatment (including but notlimited to advanced MSS colorectal cancer);

• ECOG physical status score 0~1;

• Expected survival ≥3 months;

• At least one evaluable lesion according to the solid tumor response criteria (RECISTversion 1.1). Note: If the only evaluable disease site has previously receivedradiation therapy, it can be considered an evaluable lesion after determiningdisease progression;

• Major organ and bone marrow functions meet the following criteria within 7 daysprior to initial dosing:

1. Blood routine: neutrophils ≥1.5×109/L, platelets > 100×109/L, hemoglobin ≥90g/L(no blood transfusion, no supportive treatment with G-CSF and other drugswithin 2 weeks before screening);

2. Liver function: General patients: alanine aminotransferase (ALT) and/oraspartate aminotransferase (AST)≤3× upper limit of normal; Total bilirubin ≤1.5× upper limit of normal value; Patients with liver metastasis: ALT and/orAST ≤5× upper limit of normal;

3. Renal function: serum creatinine (Cr)≤1.5× upper limit of normal value orcreatinine clearance CCr≥60ml/min(using Cockcroft-Gault formula: The Ccr (ml/min) = [(140 - age) * weight kg * F] / [serum creatinine (mg/dl) x 72] (F = 1 male, the female F = 0.85).

4. Coagulation function: prothrombin time (PT)≤ 1.5×ULN or InternationalNormalized ratio (INR)≤ 1.5×ULN, and activated partial thromboplastin time (APTT)≤ 1.5×ULN;

• The blood pregnancy results of fertile female subjects within 7 days prior to thefirst dosing must be negative. Female subjects were willing to use highly effectivecontraception during the trial and for at least 90 days after the last dose of thetrial drug. Male subjects were willing to use highly effective contraception duringthe trial and for at least 90 days after the last dose of the trial drug.

Exclusion Criteria:

• Severe systemic reactions or side effects due to prior smallpox vaccination;

• Patients with known to be allergic to the test drug or its excipients;

• Patients with a history of other tumors within 5 years prior to screening, excludingeffectively resected cervical carcinoma in situ, low-risk gastrointestinal stromaltumor, breast cancer, cutaneous basal cell carcinoma, cutaneous squamous cellcarcinoma, and papillary thyroid carcinoma;

• Patients with untreated symptomatic central nervous system metastases (CNS) who meetone of the following criteria can be enrolled:

1. CNS metastasis is asymptomatic and does not require treatment;

2. The CNS metastases have been treated, neurological symptoms have returned tobaseline (except for treatment-related residual signs or symptoms),glucocorticoids have been discontinued for at least 2 weeks prior torandomization, and imaging studies within 28 days prior to randomizationsuggest that the CNS lesions are radiographically stable.

• Pial metastasis;

• Subjects with uncontrolled pleural effusion, pericardial effusion, or ascitesrequiring repeated drainage;

• Previous acceptance of oncolytic viruses, stem cells or gene therapy products;

• Patients with received systemic antitumor therapy, including but not limited tochemotherapy, endocrine therapy, and immunotherapy, within 4 weeks before the firstdose; Oral small-molecule targeted drugs are administered 2 weeks before the firstdose or within 5 half-lives of the drug (whichever is longer); Palliativeradiotherapy within 14 days before the first dose; Participated in clinical trialsof other antitumor drugs within 4 weeks; Received any Chinese herbal medicine orproprietary Chinese medicine for any anti-tumor indication within 2 weeks prior toinitial administration;

• The adverse reactions of previous anti-tumor therapy have not returned to CTCAE 5.0grade evaluation ≤ Class 1 (except toxicity judged by the investigator to have nosafety risk);

• Patients with received surgery or interventional treatment (excluding tumor biopsy,puncture, etc.) or unhealed wounds, ulcers or fractures within 4 weeks prior to the ≥90g/L(no blood transfusion, no supportive treatment with G-CSF and other drugs
within 2 weeks before screening);
 

2. Liver function: General patients: alanine aminotransferase (ALT) and/or
aspartate aminotransferase (AST)≤3× upper limit of normal; Total bilirubin
 ≤1.5× upper limit of normal value; Patients with liver metastasis: ALT and/or
AST ≤5× upper limit of normal;
 
3. Renal function: serum creatinine (Cr)≤1.5× upper limit of normal value or
creatinine clearance CCr≥60ml/min(using Cockcroft-Gault formula: The Ccr
 (ml/min) = [(140 - age) * weight kg * F] / [serum creatinine (mg/dl) x 72] (F =
 1 male, the female F = 0.85).
 
4. Coagulation function: prothrombin time (PT)≤ 1.5×ULN or International
Normalized ratio (INR)≤ 1.5×ULN, and activated partial thromboplastin time
 (APTT)≤ 1.5×ULN;
 

• The blood pregnancy results of fertile female subjects within 7 days prior to the
first dosing must be negative. Female subjects were willing to use highly effective
contraception during the trial and for at least 90 days after the last dose of the
trial drug. Male subjects were willing to use highly effective contraception during
the trial and for at least 90 days after the last dose of the trial drug.
 
 Exclusion Criteria:
 
• Severe systemic reactions or side effects due to prior smallpox vaccination;
 
• Patients with known to be allergic to the test drug or its excipients;
 
• Patients with a history of other tumors within 5 years prior to screening, excluding
effectively resected cervical carcinoma in situ, low-risk gastrointestinal stromal
tumor, breast cancer, cutaneous basal cell carcinoma, cutaneous squamous cell
carcinoma, and papillary thyroid carcinoma;
 
• Patients with untreated symptomatic central nervous system metastases (CNS) who meet
one of the following criteria can be enrolled:
 

1. CNS metastasis is asymptomatic and does not require treatment;
 
2. The CNS metastases have been treated, neurological symptoms have returned to
baseline (except for treatment-related residual signs or symptoms),
glucocorticoids have been discontinued for at least 2 weeks prior to
randomization, and imaging studies within 28 days prior to randomization
suggest that the CNS lesions are radiographically stable.
 

• Pial metastasis;
 

• Subjects with uncontrolled pleural effusion, pericardial effusion, or ascites
requiring repeated drainage;
 

• Previous acceptance of oncolytic viruses, stem cells or gene therapy products;
 

• Patients with received systemic antitumor therapy, including but not limited to
chemotherapy, endocrine therapy, and immunotherapy, within 4 weeks before the first
dose; Oral small-molecule targeted drugs are administered 2 weeks before the first
dose or within 5 half-lives of the drug (whichever is longer); Palliative
radiotherapy within 14 days before the first dose; Participated in clinical trials
of other antitumor drugs within 4 weeks; Received any Chinese herbal medicine or
proprietary Chinese medicine for any anti-tumor indication within 2 weeks prior to
initial administration;
 

• The adverse reactions of previous anti-tumor therapy have not returned to CTCAE 5.0
grade evaluation ≤ Class 1 (except toxicity judged by the investigator to have no
safety risk);
 

• Patients with received surgery or interventional treatment (excluding tumor biopsy,
puncture, etc.) or unhealed wounds, ulcers or fractures within 4 weeks prior to the
first dose;

• Patients with a history of severe cardiovascular and cerebrovascular disease,including but not limited to: congestive heart failure ≥ Class II of the New YorkHeart Association (NYHA); Left ventricular ejection fraction (LVEF)<50%; QT interval (QTcF)>470ms as corrected by the Fridericia method or prolonged QT intervalsyndrome; Acute coronary syndrome, aortic dissection, severe arrhythmia, stroke, orother grade 3 or higher cardiovascular and cerebrovascular events occurred within 6months before the first treatment; Hypertension poorly controlled by standardtreatment (systolic blood pressure ≥140mmHg or diastolic blood pressure ≥90mmHg);

• Patients with a history of exfoliated skin that requires systemic treatment (such aseczema or ectopic dermatitis);

• Active hepatitis B (HbsAg positive, HBV DNA test value greater than the upper limitof normal); Active hepatitis C (those with positive anti-HCV antibodies are furthertested positive for HCV RNA); A known history of immunodeficiency virus (HIV)disease or a positive HIV antibody test;

• Subject with an active infection or developed an unexplained fever > 38.5 ° C duringscreening or prior to initial administration;

• There is evidence of clinically significant immunodeficiency, such as a primaryimmunodeficiency state, such as severe combined immunodeficiency disease (SCID);Co-opportunistic infection;

• At the time of screening, patients with active autoimmune diseases such as systemiclupus erythematosus, rheumatoid arthritis, vasculitis, etc., or with a history ofautoimmune diseases that may recur, except for the following conditions: (1)Type 1diabetes; (2)Hypothyroidism (if controlled with hormone replacement therapy alone); (3)Controlled celiac disease; (4)Skin diseases that do not require systemictreatment;(5) Any other disease that will not recur in the absence of an externaltrigger;

• Subject with an active infection or developed an unexplained fever > 38.5 ° C duringscreening or prior to initial administration;are receiving long-term systemicsteroid (prednisone >10mg/ day or equivalent dose of the same drug) or any otherform of immunosuppressant therapy within 14 days prior to initial treatment;Treatment with topical, ocular, intra-articular, intranasal, and inhalationcorticosteroids is excluded; Short-term use of corticosteroids (≤10mg equivalentdose of prednisone) for preventive treatment (e.g. prevention of contrast agentallergy);

• Patients with received allogeneic tissue or solid organ transplantation;

• Other diseases or abnormalities assessed by the investigator as unsuitable forparticipation in the study.