Study on the Safety and Efficacy of Intratumoral Administration of IDOV-SAFETM in the Treatment of Advanced Solid Tumors

NCT06713148 | Not Yet Recruiting Early Phase 1

• 1 other identifier: LY001-F002
• Study Type: interventional
• Target: 42
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Advanced Malignant Solid Tumor

Outcome Measures

Primary Outcomes (2)

• Dose Limiting Toxicities (DLT)

  Dose-limiting toxicity is defined as an adverse event that is considered to be drug-related and meets one of the Protocol definitions

  up to 3 weeks

• Incidence of adverse events (AE)

  Incidence of adverse events (AE)

  through study completion, an average of 2 years

Secondary Outcomes (10)

• Levels of viral DNA in blood

  up to 3days

• T cell subsets

  through study completion, an average of 1 year

• Tumor infiltrates lymphocytes

  through study completion, an average of 1 year

• TCR spectrum analysis

  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

Study Arms (1)

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

Biological: IDOV-SAFETM

Interventions

IDOV-SAFETM BIOLOGICAL

Each patient received intratumoral injection on the first day, 14 days as a course of treatment, and the follow-up investigator decided whether to continue the second (D14) and third (D28) course of administration according to the comprehensive evaluation of the subjects' conditions

Oncolytic Virus injection(IDOV-SAFETM)

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \~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 1.
• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Fudan University: lead

Study Officials

• Hongxia Wang, PhD

  Fudan University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jianhua Chen, PhD

CONTACT

17321168230; jianhuachen15@163.com

Hongxia Wang, PhD

CONTACT

021-33988888; whx365@126.com

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Chief of Internal Medicine

Study Record Dates

• First Submitted: September 11, 2024
• First Posted: December 3, 2024
• Study Start: April 10, 2025
• Primary Completion: December 31, 2025
• Study Completion (Estimated): December 31, 2027
• Last Updated: February 6, 2025

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will not share