Histologically or cytologically confirmed advanced malignant solid tumors that have progressed after, or are intolerant to, standard therapies, or for which no effective standard treatment currently exists (including, but not limited to, advanced MSS-type colorectal cancer).
Conditions
Interventions
Gemcitabine and PD-1 monoclonal antibody, dosing regimen determined by investigator
Dose Expansion Phase C Group (Monotherapy Expansion):IDOV-SAFETM 3x10^9 pfu or 1x10^10 pfu, intravenous infusion, every 3 weeks (Day 1, Day 5)
Dose Escalation Study 1, Dose Group 1 (1x10^9 pfu):IDOV-SAFETM 1x10^9 pfu, intravenous infusion, every 3 weeks (Day 1, Day 5), accelerated titration
Dose Escalation Study 1, Dose Group 2 (3x10^9 pfu):IDOV-SAFETM 3x10^9 pfu, intravenous infusion, every 3 weeks (Day 1, Day 5), 3+3 design
Dose Escalation Study 1, Dose Group 3 (1x10^10 pfu):IDOV-SAFETM 1x10^10 pfu, intravenous infusion, every 3 weeks (Day 1, Day 5), 3+3 design
Dose Escalation Study 1, Dose Group 4 (3x10^10 pfu):IDOV-SAFETM 3x10^10 pfu, intravenous infusion, every 3 weeks (Day 1, Day 5), 3+3 design
Dose Escalation Study 2, Dose Group 1 (3x10^9 pfu):IDOV-SAFETM 3x10^9 pfu, intravenous infusion, every 3 weeks (Day 1, Day 5), accelerated titration
Dose Escalation Study 2, Dose Group 2 (1x10^10 pfu):IDOV-SAFETM 1x10^10 pfu, intravenous infusion, every 3 weeks (Day 1, Day 5), 3+3 design
Dose Escalation Study 2, Dose Group 3 (3x10^10 pfu):IDOV-SAFETM 3x10^10 pfu, intravenous infusion, every 3 weeks (Day 1, Day 5), 3+3 design
Dose Expansion Phase A Group (Monotherapy + Yiwoxi Monoclonal Antibody):IDOV-SAFETM 3x10^9 pfu or 1x10^10 pfu, intravenous infusion, every 3 weeks (Day 1, Day 5)
Yiwoxi monoclonal antibody, dosing regimen determined by investigator
Dose Expansion Phase B Group (Monotherapy + Gemcitabine ± PD-1 Monoclonal Antibody):IDOV-SAFETM 3x10^9 pfu or 1x10^10 pfu, intravenous infusion, every 3 weeks (Day 1, Day 5)
Sponsors
Cancer Hospital Chinese Academy of Medical Sciences
Eligibility
Sex/Gender
All
Age
18 Years to 75 Years
Inclusion criteria
Inclusion criteria: 1. Understand and voluntarily sign the written informed consent form; 2. Male and female subjects aged >=18 years and =3 months; 6. At least one measurable lesion according to RECIST version 1.1 criteria. Note: If the only measurable lesion site was previously treated with radiotherapy, it may be considered measurable after confirmation of disease progression; 7. Major organ and bone marrow function must meet the following criteria within 7 days prior to first dose: (1) Hematology: Absolute neutrophil count >=1.5×10^9/L, platelets >100×10^9/L, hemoglobin >=90 g/L (no blood transfusion or G-CSF use within 2 weeks prior to screening); (2) Liver function: In general patients: ALT and/or AST =60 mL/min (calculated by Cockcroft-Gault formula: Ccr [mL/min] = [(140 - age) × body weight (kg) × F] / [serum creatinine (mg/dL) × 72], where F = 1 for males and F = 0.85 for females); (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; 8. Female subjects of childbearing potential must have a negative serum pregnancy test within 7 days prior to first dose. Female subjects must agree to use highly effective contraception during the trial and for at least 90 days after the last dose of study drug. Male subjects must agree to use highly effective contraception during the trial and for at least 90 days after the last dose of study drug.
Exclusion criteria
Exclusion criteria: 1.A history of severe systemic reactions or adverse effects following previous smallpox vaccination; 2.Subjects with known hypersensitivity to the investigational product or any of its excipients; 3.A history of other malignancies within 5 years prior to screening, with the exception of effectively resected carcinoma in situ of the cervix, low-risk gastrointestinal stromal tumors, breast cancer, basal cell carcinoma of the skin, cutaneous squamous cell carcinoma, and papillary thyroid carcinoma; 4.Untreated symptomatic central nervous system (CNS) metastases. Subjects may be enrolled if they meet one of the following criteria: (1)Asymptomatic CNS metastases that do not require treatment; (2) CNS metastases that have received treatment, with neurological symptoms restored to baseline levels (excluding residual signs or symptoms related to treatment), systemic glucocorticoids discontinued for at least 2 weeks prior to randomization, and imaging examinations within 28 days prior to randomization demonstrating radiological stability of CNS lesions; 5.Leptomeningeal metastasis; 6.Subjects with uncontrolled pleural effusion, pericardial effusion, or ascites requiring repeated drainage; 7.Subjects with a prior history of receiving oncolytic virus, stem cell, or gene therapy products; 8.Subjects who have received systemic anti-tumor therapy within 4 weeks prior to the first dose administration, including but not limited to chemotherapy, endocrine therapy, and immunotherapy; for oral small-molecule targeted drugs, the interval shall be at least 2 weeks prior to the first dose administration or 5 half-lives of the drug, whichever is longer. Subjects who have undergone palliative radiotherapy within 14 days prior to the first dose administration; subjects who have participated in clinical trials of other anti-tumor drugs within 4 weeks; subjects who have taken Chinese herbal medicines or proprietary Chinese medicines for any anti-tumor indication within 2 weeks prior to the first dose administration; 9.Subjects whose adverse reactions from prior anti-tumor therapy have not recovered to = Grade II; left ventricular ejection fraction (LVEF) 470 ms or a history of long QT syndrome; acute coronary syndrome, aortic dissection, severe arrhythmia, stroke, or other Grade 3 or higher cardiovascular and cerebrovascular events occurring within 6 months prior to the first treatment; poorly controlled hypertension under standard therapy (systolic blood pressure >= 140 mmHg or diastolic blood pressure >=90 mmHg); 12.Subjects with a history of exfoliative skin diseases requiring systemic therapy (e.g., eczema or atopic dermatitis); 13.Subjects with active hepatitis B (positive for HBsAg and HBV DNA level exceeding the upper limit of normal); active hepatitis C (positive for anti-HCV antibodies with confirmatory positive HCV
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The occurrence and frequency of dose-limiting toxicity (DLT) during the study period.;The occurrence and frequency of Adverse Events (AEs) and Serious Adverse Events (SAEs);Maximum tolerated dose (MTD) or maximum dosing dose (MFD; | — |
Secondary
| Measure | Time frame |
|---|---|
| Pharmacodynamic Indicators – Change in tumor markers from baseline (colorectal cancer: collect carcinoembryonic antigen (CEA), carbohydrate antigen 199 (CA199), and alpha-fetoprotein (AFP)).;Efficacy Endpoint - Objective Response Rate (ORR), Disease Control Rate (DCR), Duration of Response (DOR), and Progression-Free Survival (PFS).;Pharmacodynamic Indicators: Change from baseline in T-cell subsets (including CD4+ and CD8+);Efficacy Endpoints;Pharmacodynamic Indicators: Cytokines IL-4, IL-6, IL-10, IFN-?, TNF-a, etc.;Pharmacokinetic Indicators — Levels of viral DNA in blood, saliva, and urine.;Efficacy Endpoint - Overall Survival (OS);Pharmacokinetic Indicator — Level of viral DNA in tumor tissue (non-mandatory); | — |
Countries
China
Contacts
Public ContactLi Ning
Cancer Hospital Chinese Academy of Medical Sciences
Outcome results
None listed