A Clinical Study on Oncolytic Virus Injection (R130) for the Treatment of Relapsed/Refractory Bone and Soft Tissue Tumors

A Clinical Safety and Efficacy Study on Oncolytic Virus Injection (R130) for the Treatment of Relapsed/Refractory Bone and Soft Tissue Tumors

20 participants are expected to be enrolled for this open，Single-armed clinical trial to evaluate the safety and efficacy of the recombinant herpes simplex virus Ⅰ, R130 in patients with relapsed/refractory bone and soft tissue tumors.

Study Overview

• Status: Recruiting
• Conditions: Sarcoma; Osteosarcoma; Sarcoma,Soft Tissue; Bone Tumor
• Intervention / Treatment: Drug: Recombinant oncolytic herpes simplex virus type Ⅰ (R130)

• Study Type: Interventional
• Enrollment (Anticipated): 20
• Phase: Early Phase 1

Contacts and Locations

• Study Contact: Name: Feng Pan, MD; Phone Number: +8613764868528; Email: pf@jxyymedtech.com

Study Locations

• China
  • Shaanxi
    • Xi'an, Shaanxi, China, 710000
      • Recruiting
      • Xi'an Honghui Hospital
      • Contact: Zhichao Tong, Ph.D; Phone Number: +86 13629209267; Email: zhichaotong@126.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Age 14 to 75 years, diagnosed with soft tissue sarcoma or bone neoplasms clearly by histology and/or cytology.
2. Failure of standard treatment or patient unwillingness to receive other antitumor therapy.
3. No absolute or relative centasis contraindiction.
4. Subjects with ECoG score of 0-2.
5. Expected survival of 3 months or more.
6. Have at least one measurable lesion (according to RECIST 1.1 criteria) that is amenable to intratumoral drug delivery.
7. Subjects must have appropriate organ function, and laboratory tests during the screening period must meet the following requirements: a) absolute neutrophil count (ANC) ≥ 1.5 × 109/L, platelets (PLT) ≥ 80 × 109/L, and hemoglobin (Hb) ≥ 85 g/L; b) serum creatinine (Cr) and blood urea nitrogen (BUN) within 1.5 times the upper limit of normal values; c) serum total bilirubin (TBIL) ≤ 2 times the upper limit of normal values; d) glutamic aminotransferase (ALT) and glutamic oxalacetic aminotransferase (AST) ≤ 2.5 times the upper limit of normal values; subjects with liver metastases do not exceed 5 times the upper limit of normal values; e) activated partial thromboplastin time (APTT), prothrombin time (PT) within 1.5 times the upper limit of normal values.
8. Any treatment for malignancy, including radiotherapy, chemotherapy and biological agents, must be discontinued 28 days prior to R130 treatment.
9. Eligible patients of childbearing potential must agree to use a reliable method of contraception (hormonal or barrier method or abstinence) with their partner for the duration of the trial and for at least 180 days after the last dose; female patients of childbearing potential must have a negative urine pregnancy test within 7 days prior to enrollment.
10. Subjects voluntarily sign an informed consent form and are in good compliance.

Exclusion Criteria:

1. Have had any serious adverse reactions associated with immunotherapy and have not recovered to CTCAE 5.0 grade rating 0 or 1 level of toxicity after previous antineoplastic therapy.
2. Subjects with any severe and/or uncontrolled disease, including: a) poorly controlled hypertension (systolic blood pressure ≥ 150 mmHg or diastolic blood pressure ≥ 100 mmHg); b) suffering from class I or higher myocardial ischemia or myocardial infarction, arrhythmia (QTc ≥ 470 ms and ≥ grade 2 congestive heart failure (New York Heart Association (NYHA) classification); c) active or uncontrolled severe infection (≥ CTCAE grade 2 infection); d) Patients with previous organ transplantation, bone marrow transplantation (hematopoietic stem cell transplantation) and severe immune deficiency; e) Urine routine suggesting urine protein ≥++ and confirmed 24-hour urine protein quantification > 1.0 g.
3. Patients with past history of type I diabetes mellitus or HIV.
4. Severe abnormalities in thyroid and cortisol testing; active, known or suspected autoimmune disease requiring systemic therapy.
5. Patients with active tuberculosis and a strong positive OT test.
6. Patients with active bleeding or severe coagulation dysfunction.
7. Have had antitumor therapy, including endocrine, chemotherapy, radiotherapy, targeted therapy, immunotherapy and antitumor herbal therapy, 4 weeks prior to the first dose.
8. Current active hepatitis B, active hepatitis C, immunodeficiency virus or other active infection of clinical significance.
9. Patients who have undergone surgery of grade 3 or higher or whose surgical wounds have not healed within 4 weeks prior to enrollment.
10. Pregnant, lactating and planning to have children within six months.
11. Subjects who, in the judgment of the investigator, are unsuitable for participation in this trial for any reason.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: R130 Treatment Group; Every 7-14 days,1-6 ml R130 （concentration of 1x10^8 plaque-forming Units/mL,PFU/mL）will be injected intratumoral in patients with relapsed/refractory bone and soft tissue tumors.	Drug: Recombinant oncolytic herpes simplex virus type Ⅰ (R130); R130, a modified herpes simplex virus-Ⅰ (HSV-1) containing the gene coding for anti-CD3 scFv/CD86/PD1/HSV2-US11; Other Names: Oncolytic virus Injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Subject incidence of adverse events.	To characterize the safety profile of R130 injection in patients with relapsed/refractory bone and soft tissue tumors as measured by the incidence of Grade ≥ 3 Common Terminology Criteria for Adverse Events, version 5.0 (CTCAE v5.0)	Up to 6 months
Subject incidence of laboratory abnormalities	Detection of liver and renal function, electrocardiogram, routine blood examination etc.	Up to 1 month
Systemic Immune Response	Detection of increased systemic immune Response markers in sera (IL2,IL4,IL6,IL8,IL10,TNFa，IFNγ, etc.) and peripheral blood mononuclear cells by multi-Color fluorescence-activated cell sorting (FACS)	Up to 6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Quality of Life Assessment	Evaluate with EORTC QLQ-C30	Every 6 weeks for 12 months
Disease Assessment for Disease Control Rate	Evaluate the efficacy endpoints of DCR by the investigator with RECIST v1.1 and iRECIST	Every 10 weeks for 12 months
Disease Assessment for Duration of Response	Evaluate the efficacy endpoints of DOR by the investigator with RECIST v1.1 and iRECIST	Every 10 weeks for 12 months

Collaborators and Investigators

• Sponsor: Shanghai Yunying Medical Technology
• Collaborators: Xi'an Honghui Hospital

Study record dates

Study Major Dates

• Study Start (Actual): April 10, 2023
• Primary Completion (Anticipated): April 1, 2025
• Study Completion (Anticipated): April 1, 2026

Study Registration Dates

• First Submitted: April 25, 2023
• First Submitted That Met QC Criteria: May 8, 2023
• First Posted (Actual): May 9, 2023

Study Record Updates

• Last Update Posted (Actual): May 9, 2023
• Last Update Submitted That Met QC Criteria: May 8, 2023
• Last Verified: April 1, 2023

More Information

Terms related to this study

• Keywords: Immunotherapy; Oncolytic virus; Herpes simplex virus type 1
• Additional Relevant MeSH Terms: Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Neoplasms, Bone Tissue; Neoplasms, Connective Tissue; Sarcoma; Osteosarcoma; Soft Tissue Neoplasms
• Other Study ID Numbers: XAHH-R130-BSTT

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

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