Overview
This is an open-label, dose escalation study of the safety and tolerability of oncolytic
virus injection(RT-01) when administered via Intravenous injection in patients with advanced
solid tumors.
The purpose of this study is to assess the safety and tolerability of RT-01 and to determine
the recommended phase 2 dose (RP2D) for further study. The study will also evaluate antitumor
activity, objective response rate, pharmacokinetics and virus shedding of RT-01.
Description
This is an investigator initiated , open-label, study of RT-01 given via intratumoral (IT)
injection as a single agent and in combination with IV PD-1/PD-L1 in participants with
advanced solid tumors.
The study consists of two parts：In the single agent dose escalation part (Part A), four doses
(1×10^7 TCID50, 1×10^8 TCID50, 3×10^8 TCID50, 1×10^9 TCID50) of RT-01 will be delivered
Intravenous as single agent to observe the DLTs and to identify the MTD. Part A is a single
agent dose escalation which will use a 3+3 design to evaluate escalating doses of RT-01.
Once the IV RT-01 MTD is established, the Part B part of the study will begin. Part B is IV
RT-01 in combination with IV PD-1/PD-L1 dose escalation which will use a 3+3 design to
evaluate escalating doses of IV RT in combination with IV pembrolizumab.
Total enrollment will depend on the toxicities and/or activity observed, with approximately
16-36 evaluable participants enrolled.
The primary study objective is to determine the safety, tolerability, and maximum tolerated
dose (MTD) of Intravenous administration of RT-01 as a single agent and in combination with
immune checkpoint inhibitors. Secondary objectives will assess efficacy overall response
rate, as well as disease control rate, progression free survival, duration of response, and
anti-tumor immune responses.
Eligibility
Inclusion Criteria:
- Male or female aged ≥ 18 years;
- Subjects must have histologically- or cytologically-confirmed diagnosis of advanced solid tumor(s) and have progressed on or is not eligible for available standard therapy;
- 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 consent form, had good compliance, and cooperated with the follow-up.
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.