A Clinical Study of Intratumoral Administration of RT-01 in Patients With Advanced Solid Tumors

An Open-Label, Dose Escalation Study of the Safety and Tolerability of Oncolytic Virus Injection(RT-01) When Administered Via Intratumoral Injection in Patients With Advanced Solid Tumors

This is an open-label, dose escalation study of the safety and tolerability of oncolytic virus injection(RT-01) when administered via intratumoral 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.

Study Overview

• Status: Recruiting
• Conditions: Solid Tumor; Advanced Cancer
• Intervention / Treatment: Biological: Oncolytic Virus Injection(RT-01)

Detailed Description

This is an investigator initiated , open-label, study of RT-01 given via intratumoral (IT) injection as a single agent in participants with advanced solid tumors. The study is a single agent dose escalation which will use a 3+3 design to evaluate escalating doses of RT-01. Total enrollment will depend on the toxicities and/or activity observed, with approximately 7-18 evaluable participants enrolled.

The primary study objective is to determine the safety, tolerability, and maximum tolerated dose (MTD) of intratumoral administration of RT-01 as a single agent. 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.

• Study Type: Interventional
• Enrollment (Anticipated): 18
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Jiangsu
    • Wuxi, Jiangsu, China, 214043
      • Recruiting
      • Wuxi People's Hospital
      • Contact: Peihua Lu, MD; Phone Number: 13621500031; Email: 13625653@qq.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SEQUENTIAL
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

EXPERIMENTAL: Oncolytic virus injection(RT-01) for patients with advanced solid tumors; Intratumoral administration of RT-01 as single agent for patients with advanced solid tumors.The injection dose of RT-01 was determined by the lesion size: mL for lesion length <1.5 cm;; mL for lesion length between 1.5 cm and 2.5 cm;; mL for lesion length between 2.5 cm and 5.0 cm;; mL for lesion length between >5 cm

Biological: Oncolytic Virus Injection(RT-01); Administered by intratumoral injection for 3 dose cohorts: 1×10^7 TCID50/mL, 1×10^8 TCID50/mL and 7×10^8 TCID50/mL

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Dose Limiting Toxicities (DLT)	To define the maximum tolerated dose (MTD) of intratumoral administration of RT-01 injection in humans with malignant tumors.	Up to 28 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with laboratory value abnormalities and/or adverse events	Number of participants with potentially clinically significant laboratory values	Up to 6 months
Safety and tolerability assessed by Adverse Events (AEs)	An AE is any untoward medical occurrence in a subject administered an investigational product (IP), and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of IP whether or not considered related to the IP	Up to 6 months
Number of participants with vital sign abnormalities and /or adverse event	Number of participants with potentially clinically significant vital sign values	Up to 6 months
Safety assessed by 12- lead electrocardiograms (ECGs) adverse events	12-lead ECGs will be read and assessed locally. Any clinically significant adverse changes on the ECG will be reported as Adverse Events	Up to 6 months
To evaluate the efficacy assessed per RECIST and iRECIST	Changes in tumor size and occurrence of metastases was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST). Complete Response is disappearance of all target lesions. Partial Response is at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum of diameters. Progressive Disease is at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). And Stable Disease is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum of diameters while on study.	Up to 2 years form first dose of RT-01
Number of Participants With Response	Detection of increased systemic immune Response markers in peripheral blood mononuclear cells	at baseline, 2, 4, 7, 14, 28 days after injection
Viral shedding of RT-01 in blood	Viral DNA will be analyzed by quantitative polymerase chain reaction (qPCR).	Up to 6 months
Presence of neutralizing antibodies of antidrug antibodies (ADAs) development	To evaluate the immunogenicity of RT-01 given as single agent post injection	Up to 6 months

Collaborators and Investigators

• Sponsor: Wuxi People's Hospital

Study record dates

Study Major Dates

• Study Start (ACTUAL): November 1, 2021
• Primary Completion (ANTICIPATED): June 1, 2022
• Study Completion (ANTICIPATED): June 1, 2023

Study Registration Dates

• First Submitted: November 1, 2021
• First Submitted That Met QC Criteria: November 15, 2021
• First Posted (ACTUAL): November 30, 2021

Study Record Updates

• Last Update Posted (ACTUAL): January 31, 2022
• Last Update Submitted That Met QC Criteria: January 19, 2022
• Last Verified: January 1, 2022

More Information

Terms related to this study

• Keywords: immunotherapy; oncolytic virus; RT-01; intratumoral injection
• Additional Relevant MeSH Terms: Neoplasms
• Other Study ID Numbers: LWY21076C1

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No