A Clinical Study on Oncolytic Virus Injection (R130) for the Treatment of Advanced Solid Tumors

A Clinical Safety and Efficacy Study on Oncolytic Virus Injection (R130) for the Treatment of Advanced Solid 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 advanced solid tumors.

Study Overview

• Status: Recruiting
• Conditions: Sarcoma; Carcinoma; Breast Cancer; Gynecologic Cancer; Gastric Cancer; Colorectal Cancer; Pancreatic Cancer; Lung Cancer; Liver Cancer
• Intervention / Treatment: Drug: Recombinant oncolytic herpes simplex virus type 1 (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
  • Jiangsu
    • Shanghai, Jiangsu, China, 221000
      • Recruiting
      • Xuzhou Second People's Hospital
      • Contact: Zhengxiang Han, MD,PhD; Phone Number: +86 18052268612; Email: cnhzxyq@163.com
      • Principal Investigator: Zhengxiang Han, MD

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Patients with solid tumors clearly diagnosed by histology and/or cytology.
2. Failure of standard treatment or patient unwillingness to receive other antitumor therapy.
3. Age 18 to 75 years.
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 or intraperitoneal 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 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. No absolute or relative centasis contraindiction.
9. Eligible patients of childbearing potential must agree to use a reliable method of contraception 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.
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 severe prior interstitial lung changes (as determined by the investigator).
6. Patients with active tuberculosis and a strong positive OT test.
7. Patients with active bleeding or severe coagulation dysfunction.
8. Have had antitumor therapy, including endocrine, chemotherapy, radiotherapy, targeted therapy, immunotherapy and antitumor herbal therapy, 4 weeks prior to the first dose.
9. Have not recovered to CTCAE 4.0 grade rating 0 or 1 level of toxicity after previous antineoplastic therapy.
10. Current active hepatitis B, active hepatitis C, immunodeficiency virus or other active infection of clinical significance.
11. Patients who have undergone surgery of grade 3 or higher or whose surgical wounds have not healed within 4 weeks prior to enrollment.
12. Pregnant, lactating and planning to have children within six months.
13. 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,1-4 ml R130 （concentration of 1x10^8 plaque-forming Units/mL,PFU/mL）will be injected intratumoral or intraperitoneal in patients with advanced solid tumors	Drug: Recombinant oncolytic herpes simplex virus type 1 (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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
Subject incidence of adverse events	To characterize the safety profile of R130 injection in patients with advanced solid 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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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

Other 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 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: The Affiliated Hospital of Xuzhou Medical University

Study record dates

Study Major Dates

• Study Start (Actual): March 2, 2023
• Primary Completion (Anticipated): March 2, 2025
• Study Completion (Anticipated): March 2, 2026

Study Registration Dates

• First Submitted: May 8, 2023
• First Submitted That Met QC Criteria: May 8, 2023
• First Posted (Actual): May 16, 2023

Study Record Updates

• Last Update Posted (Actual): May 16, 2023
• Last Update Submitted That Met QC Criteria: May 8, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Keywords: Immunotherapy; Oncolytic virus; Herpes simplex virus type 1
• Other Study ID Numbers: XYFY-R130-AST

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