A Study of Oncolytic Virus Injection (RT-01) in Combination With PD-1 Inhibitor in Patients With Advanced Solid Tumors

Study Overview
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Brief Summary
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This is a single-arm, open-label, exploratory study to evaluate safety and efficacy of oncolytic virus injection(RT-01) in combination with PD-1 inhibitor (Nivolumab) in patients with advanced solid tumors. The purpose of this study is to evaluate the safety and tolerability, antitumor activity, The immunoreactivity, The immunogenicity, pharmacokinetics and virus shedding of RT-01 in combination with PD-1 inhibitor.

Detailed Description
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This is an investigator initiated , single-arm, open-label study of RT-01 as a single agent given via Intravenous injection（IV）with or without Intratumoral injection（IT） in combination with IV Nivolumab in patients with advanced solid tumors. This study is planned to enroll 40-50 patients with advanced solid tumors. RT-01 will be administered as a single dose on day 1, Nivolumab will be administered intravenously every 3 weeks starting on day 5. The purpose of this study is to assess the safety and tolerability, antitumor activity, The immunoreactivity, The immunogenicity, pharmacokinetics and virus shedding of RT-01 in combination with PD-1 Inhibitor (Nivolumab).

Official Title
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A Single-Arm, Open-Label, Exploratory Study to Evaluate Safety and Efficacy of Oncolytic Virus Injection (RT-01) in Combination With PD-1 Inhibitor (Nivolumab) in 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; Subjects must have histologically or cytologically confirmed diagnosis of advanced solid tumor(s) who have failed in standard therapy (disease progression or intolerance) and no effective treatment, or have no standard therapy, or have failed to obtain standard treatment due to objective conditions ; Subjects have 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 coagulation 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; Voluntarily participated in this study, signed the informed 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 2 weeks before RT-01 administration； Subjects who have participate in another interventional study within 4 weeks before RT-01 administration； Subjects who have had major surgery within 4 weeks before RT-01 administration； 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 before RT-01 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 use of corticosteroids； Subjects who have participate in another oncolytic virus study within 8 weeks before RT-01 administration； Subjects received live vaccines within 7 days before RT-01 administration； Subjects received Antiviral drugs within 2 weeks, long-acting interferon within 4 weeks before RT-01 administration； Subjects with adverse reactions caused by previous anti-tumor treatment not recovered to (CTCAE 5.0) grade 1 (except alopecia); Subjects who have uncontrolled 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: Oncolytic Virus Injection(RT-01)<br>RT-01 will be administered either intravenously or with a combination of intravenously and intratumorally on day 1. Nivolumab will be administered intravenously every 3 weeks starting on day 5. | Biological: Oncolytic Virus Injection(RT-01)<br>* Intravenous injection with or without intratumoral injection of a single dose of RT-01 and intravenous infusion of Nivolumab<br>|

What is the study measuring?
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Primary 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 | 
| Objective response rate | Assess the proportion of patients who achieved complete or partial response | Up to 2 years | 
| Disease control rate | Assess the proportion of patients who achieved complete or partial or stable response | Up to 2 years | 
| The changes from baseline of lymphocyte counts | The changes from baseline of Peripheral blood lymphocyte subtypes counts | Up to 28 days | 
| The concentration of antiviral antibody. | The concentration of antiviral antibody of RT-01 in blood | Up to 22 Weeks | 
| The rate of subjects with viral shedding of RT-01 | The rate of subjects with viral RNA in the secretion | Up to 22 Weeks | 
| The Tmax of Viral RNA in blood | Time to peak viral RNA concentration | Up to 22 Weeks | 
| The Cmax of Viral RNA in blood | The peak viral RNA concentration | Up to 22 Weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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RT-01, Oncolytic Virus, PD-1 Inhibitor, immunotherapy, immune Checkpoint Inhibitors, Intravenous Injection, Intratumoral injection