NCT06713148Not yet recruitingPhase 1
A Phase I Clinical Study on the Safety and Efficacy of Intratumoral Administration of IDOV-SAFETM in the Treatment of Advanced Solid Tumors
Conditions
Interventions
Drugs
Trial Snapshot
- Phase
- Phase 1
- Status
- Not yet recruiting
- Sponsor
- Fudan University
- Enrollment
- 42
- Primary Endpoint
- Dose Limiting Toxicities (DLT)
Study Overview
Brief Summary
This is an open-label, dose escalation, phase I study to evaluate safety tolerability, MTD, pharmacokinetic profile, immunogenicity, and pharmacodynamic profile of intratumoral Administration of IDOV-SAFETM in patients with advanced solid tumors.
Detailed Description
The therapeutic dose for mice was 1x10^8 PFU, and the maximum starting dose for humans was 2.67x10^9 PFU based on the Guidelines for Estimating the Maximum Recommended Starting Dose for the First Clinical Trial of Healthy Adult Volunteers.
Dose escalation phase:
At this stage, the investigators plan to enroll about 13-25 patients with advanced malignant solid tumors confirmed by histology or cytology after failure of standard treatment or without standard treatment in China for intratumoral injection of IDOV-SAFETM.
This phase consisted of five dose groups: 1x10^8 PFU, 3x10^8 PFU, 7x10^8 PFU, 1x10^9 PFU and 3x10^9 PFU. The first dose group included 1 subject, and the other dose groups were increased by "3+3", with 3-6 subjects in each group. Each patient received intratumoral injection on the first day, 14 days as a course of treatment. The follow-up investigator decided whether to continue the second (D14) and third (D28) course of administration according to the comprehensive assessment of the subjects' conditions; All subjects in each dose group may be incremented to the next dose group after completing a safety assessment 21 days after the first dose.
The dose escalation or setting may be adjusted as determined by the Safety Committee (SMC).
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Sequential
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to 75 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •18 ~75 years old, gender is not limited;
- •During screening, patients with advanced malignant solid tumors confirmed by histology or cytology (mainly including breast cancer (triple-negative priority), melanoma, head and neck tumors, and gastrointestinal cancers such as colorectal cancer, cholangiocarcinoma, pancreatic cancer, and liver cancer with intratumoral injection conditions).
- •At the time of screening, the disease has progressed after or during standard treatment; Or subjects with advanced malignant solid tumors who currently have no standard treatment available or are intolerant to chemotherapy.
- •Tumor lesions and/or metastases with at least one evaluable lesion that is subcutaneously accessible or can be injected under imaging guidance, according to the solid tumor response criteria (RECIST version 1.1).
- •When screening, the ECOG score of physical strength score is 0 or
- •Life expectancy assessed by the investigator at the time of screening was ≥3 months.
- •Subjects had adequate organ function at baseline:
- •a) Bone marrow function (no growth factor support therapy or component transfusion within 14 days prior to screening) : i. Neutrophil absolute value (ANC) ≥1.5×10^9/L; ii. Hemoglobin (HB) ≥90g/L; iii. Platelet count (PLT) ≥75×10^9/L; b) Liver function: i. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 1.5 times the upper limit of normal (ULN) (ALT and AST≤ 3 times ULN for liver metastasis or hepatocellular carcinoma); ii. Blood total bilirubin ≤1.5 ULN (in subjects with liver metastasis or hepatocellular carcinoma or Gilbert syndrome or familial benign nonbinding hyperbilirubinemia, the acceptable range of this indicator is ≤2.5 ULN); c) Renal function: serum creatinine ≤ 1.5x ULN or creatinine clearance ≥50mL/min; d) left ventricular ejection fraction (LVEF) ≥ 45%. e) Coagulation function: activated partial thromboplastin time (APTT) ≤1.5×ULN, International Standardized ratio (INR) ≤1.5×ULN.
- •Fertile female subjects must have negative blood beta-HCG test results within 7 days prior to enrollment.
- •Subjects must agree to use highly effective contraception for at least 90 days from the start of the ICF to the end of the study.
- •Be fully informed of this study and voluntarily sign ICF.
Exclusion Criteria
- •At the time of screening, advanced malignant tumors have a chance of being cured by radical treatment.
- •Asymptomatic brain metastases such as untreated ones at the time of screening; Subjects with symptomatic central nervous system (CNS) metastatic or cancerous meningitis; Or there was other evidence of uncontrolled central nervous system or meningeal metastases in subjects who were judged by the investigator to be unsuitable for enrollment.
- •Prior to enrollment, there was severe chronic or active infection: active hepatitis B (HbsAg positive, HBV DNA test value greater than the upper limit of normal); Active hepatitis C (those with positive anti-HCV antibodies are further tested positive for HCV RNA); A known history of immunodeficiency virus (HIV) disease or a positive HIV antibody test; Other conditions requiring systemic anti-infective treatment in the 4 weeks prior to initial use of the investigational drug include, but are not limited to, hospitalization for infectious complications, bacteremia, severe pneumonia, or active tuberculosis.
- •At the time of screening, patients had a history of active autoimmune diseases such as systemic lupus erythematosus, rheumatoid arthritis, vasculitis, etc., or were receiving long-term systemic steroids (prednisone >10mg/ day or equivalent doses of the same drug) or any other form of immunosuppressant therapy within 4 weeks prior to the first use of the study drug.
- •Patients with received allogeneic tissue or solid organ transplantation.
- •There is evidence of clinically significant immunodeficiency, such as primary immunodeficiency status, such as severe combined immunodeficiency disease (SCID); Combined with opportunistic infections.
- •Anticoagulants or antiplatelet drugs should be used before injection and should not be interrupted, including: aspirin should not be stopped within 7 days before injection; Coumarin that cannot be stopped within 7 days prior to injection; Direct thrombin inhibitors (such as dabigatrun) or direct factor Xa inhibitors (such as rivaroxaban, apixaban, and neperoxaban) that cannot be discontinued within 4 days prior to injection; Low molecular weight heparin (LMWH) should not be stopped within 24 hours before injection, and ordinary heparin (UFH) should not be stopped more than 4 hours before injection.
- •Patients with a history of severe cardiovascular and cerebrovascular disease, including but not limited to: congestive heart failure ≥II heart function grade of the New York Heart Association (NYHA); Left ventricular ejection fraction (LVEF) <50%; QT interval (QTcF) >470ms as corrected by the Fridericia method or prolonged QT interval syndrome; Acute coronary syndrome, aortic dissection, severe arrhythmia, stroke, or other grade 3 or higher cardiovascular and cerebrovascular events occurred within 6 months before first administration; The presence of uncontrolled hypertension (systolic blood pressure >140mmHg or diastolic blood pressure >90mmHg). Subjects with a history of hypertension are admitted to the study if their blood pressure is controlled below this standard and maintained with antihypertensive therapy.
- •Patients with received treatment with other methods, including but not limited to chemotherapy, radiotherapy, biotherapy, endocrine therapy, immunotherapy, etc., within 4 weeks prior to the first use of the investigational drug.
- •Other diseases or abnormalities assessed by the investigator as unsuitable for participation in the study.
- •Vaccination against smallpox or monkeypox within 10 years.
Arms & Interventions
Oncolytic Virus injection(IDOV-SAFETM)
Experimental
Intratumoral administration of IDOV-SAFETM every 2 weeks for patients with advanced solid tumors.
Dose cohorts: 1x10^8 PFU、3x10^8 PFU、7x10^8 PFU 、1x10^9 PFU and 3x10^9 PFU
Intervention: IDOV-SAFETM (Biological)
Outcomes
Primary Outcomes
Dose Limiting Toxicities (DLT)
Time Frame: up to 3 weeks
Dose-limiting toxicity is defined as an adverse event that is considered to be drug-related and meets one of the Protocol definitions
Incidence of adverse events (AE)
Time Frame: through study completion, an average of 2 years
Incidence of adverse events (AE)
Secondary Outcomes
- T cell subsets(through study completion, an average of 1 year)
- Levels of viral DNA in blood(up to 3days)
- Tumor infiltrates lymphocytes(through study completion, an average of 1 year)
- The level of (non-essential) viral DNA in tumor tissue(through study completion, an average of 1 year)
- Objective response rate(through study completion, an average of 1 year)
- Disease control rate(through study completion, an average of 1 year)
- During of response(through study completion, an average of 1 year)
- Overall Survival(2 years)
- TCR spectrum analysis(through study completion, an average of 1 year)
- Progression Free Survival(through study completion, an average of 1 year)
Investigators
Hongxia Wang
Chief of Internal Medicine
Fudan University
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