RT-01 Monotherapy and in Combination With Nivolumab in Patients With Advanced Solid Tumors

Study Overview
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Brief Summary
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This is a single-arm, open-lable study to determine the safety, tolerability and preliminary efficacy of oncolytic virus injection (RT-01) combined with or without immune checkpoint inhibitors (Nivolumab) in the treatment of patients with advanced solid tumors.

Detailed Description
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To evaluate the safety, tolerability, efficacy, immunoreactivity, immunogenicity, pharmacokinetics and virus shedding of RT-01 injection given via Intravenous with or without Intratumoral administration combined with immune checkpoint inhibitors Nivolumab in the treatment of patients with advanced solid tumors.

Official Title
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An Open-label Clinical Study to Evaluate the Safety and Efficacy of Intravenous With and Without Intratumoral Oncolytic Virus Injection (RT-01) Combined With or Without Immune Checkpoint Inhibitors (Nivolumab) in the Treatment of Patients With Advanced Solid Tumors

Conditions
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Advanced Solid Tumor

Intervention / Treatment
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* Biological: Oncolytic Virus Injection (RT-01）


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female aged ≥ 18 years; Have a histopathologically or cytologically confirmed dagnosis of advanced solid tumors and no existing options are felt to provide clinical benefit; At least one measurable lesion according to Response Evaluation Criteria in Solid Tumors (RECIST 1.1) (non-nodal lesions with longest diameter ≥ 10 mm, or nodal lesions with short diameter ≥ 15 mm); ECOG score of 0   2; Adequate bone marrow, hepatic and renal and cardiovascular function; Women of childbearing age who have a negative pregnancy test within 7 days before treatment. Female patients of childbearing age, and male patients with partners of childbearing age must agree to use at least one medically recognized contraceptive method during study treatment and within at least 6 months after the last dose of investigational drug; Ability to provide written informed consent. Exclusion Criteria: Subjects with known brain metastasis and/or clinically history tumor brain of metastasis； Subjects who have received anti-tumor therapy such as chemotherapy, radiotherapy, biological therapy, endocrine therapy, targeted therapy, immunotherapy, etc within 4 weeks； Subjects who have participate in another interventional study while receiving study IP within 4 weeks； Subjects who have had major surgery ≤ 4 weeks of dosing； Patients in any condition requiring systemic treatment with corticosteroids (prednisone > 10 mg/day or equivalent of the similar drug) or other immunosuppressive agents within 14 days prior to investigational drug administration, but currently or previously treated with any of the following steroid regimens, were included: Topical, ophthalmic, intra-articular, intranasal, or inhaled corticosteroids with minimal systemic absorption; Prophylactic short-term (≤ 7 days) use of corticosteroids (e.g., allergy to contrast media) or for the treatment of non-autoimmune diseases (e.g., delayed hypersensitivity caused by contact allergens)； Subjects received live vaccines within 7 days of initiation of study treatment； Subjects with adverse reactions caused by previous anti-tumor treatment not recovered to (CTCAE 5.0) grade 1 (except alopecia)； Subjects who have any active infection； Subjects with known positive history of human immunodeficiency virus (HIV) test or known acquired immunodeficiency syndrome (AIDS)； Subjects who have active hepatitis； Subjects who have serious cardiovascular system disorders history； Subjects with active autoimmune diseases or history of autoimmune diseases that may relapse； Subjects having any serious uncontrolled disease or in other conditions that would preclude them from receiving study treatment and are considered unsuitable for this study in the opinion of the investigator； Subjects in other conditions that are considered unsuitable for this study by the investigator.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intravenous Injection<br>Intravenous with or without Intratumoral RT-01 in the treatment of patients with advanced solid tumors combined with or without Nivolumab in the treatment of patients with advanced solid tumors | Biological: Oncolytic Virus Injection (RT-01）<br>* Intravenous injection of RT-01 with or without Nivolumab<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Dose Limiting Toxicities (DLT) | Graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. Defined as the highest safety-tolerated dose level where at most one patient out of six experiences dose limiting toxicities (DLT) with the next higher dose level having at least 2 of 6 patients who have experienced DLT. | Up to 28 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of adverse events | Graded according to the NCI CTCAE version 5.0. | Up to 6 months | 
| Overall response rate (ORR) | Proportion of patients in the analysis population who have complete response (CR) or partial response (PR) based on RECIST v1.1 imaging. | Up to 6 months | 
| Disease Control Rate (DCR) | Proportion of patients in the analysis population who have complete response (CR), partial response (PR) or stable disease (SD) based on RECIST v1.1 imaging. | Up to 6 months | 
| Overall Survival (OS) | Survival time is defined as the time from registration to death due to any cause. | Up to 6 months | 
| Progression Free Survival (PFS) | Progression-free survival is defined as the time from registration to the earliest date documentation of disease progression or death due to any cause. | Up to 6 months | 
| Viral replication and shedding in blood, urine and buccal swabs | Assessed via quantitative reverse transcriptase polymerase chain reaction. | Up to 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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RT-01, Oncolytic Virus Injection, Inmmune Checkpoint Inhibitors, Intravenous Injection, Intratumoral Injection