Trial Title:
The Application of Novel Oncolytic Virus in Late Stage Solid Tumors
NCT ID:
NCT06080984
Condition:
Malignant Tumor
Conditions: Official terms:
Neoplasms
Conditions: Keywords:
Solid Tumors
Oncolytic Virus
Study type:
Interventional
Study phase:
Phase 1
Overall status:
Recruiting
Study design:
Allocation:
Non-Randomized
Intervention model:
Parallel Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Oncolytic Virus SDJ001
Description:
Patients in the study receive intratumoral treatment with SDJ001 at two dose levels:
5x10^11 and 1x10^12 pfu per person. At the current dose levels, intratumoral injection is
administered on the first day of each treatment cycle. Each treatment cycle consists of
three weeks, continuing until tumor growth is observed following injection or until the
patient experiences intolerable toxic effects.
Ultrasound-guided injection may be used when necessary (2.0 mL for tumors with a diameter
>2.5 cm, 1.0 mL for diameters of 1.5-2.5 cm, 0.5 mL for diameters of 0.5-1.5 cm, and 0.1
mL for diameters <0.5 cm, with a maximum of 4 mL).
Arm group label:
Treatment Cohort 1
Intervention type:
Drug
Intervention name:
Oncolytic Virus YD06-1
Description:
Patients in the study receive intratumoral treatment with a novel oncolytic virus YD06-1
at a concentration of 10^6 pfu/mL to 10^8 pfu/ml following a dose escalation plan. Each
subject receives only one injection at the corresponding concentration, with the dose
determined based on the size of the tumor mass. (Diameter ≤1.5 cm, maximum of 1 mL;
diameter 1.5-2.5 cm, maximum of 2 mL; diameter greater than 2.5 cm, maximum of 4 mL). The
second dose is administered three weeks after the first dose, followed by subsequent
doses at two-week intervals.
Arm group label:
Treatment Cohort 2
Arm group label:
Treatment Cohort 3
Summary:
The purpose of this study is to evaluate the efficacy and safety of novel oncolytic virus
in late stage solid tumors.
Detailed description:
Oncolytic viruses (OVs) are naturally occurring or recombinant viruses that can
selectively destroy tumor cells without harming normal cells. After infecting the host,
oncolytic viruses can replicate within host cells, and the progeny viruses released can
further infect neighboring host cells and kill the tumor while triggering local or
systemic anti-tumor immune responses. Compared to traditional treatments, oncolytic virus
therapy offers advantages such as good targeting, minimal adverse reactions, multiple
tumor-killing pathways, and reduced likelihood of developing resistance.
Several clinical studies have found that oncolytic viruses can provide clinical benefits
to patients with different types, stages, and even advanced metastatic tumors.
Importantly, when used in combination with radiation therapy or chemotherapy, they
exhibit good synergistic effects. Especially when used in combination with immunotherapy,
oncolytic viruses can sensitize tumor types that were initially unresponsive to immune
checkpoint inhibitors.
Currently, oncolytic viruses are believed to exert anti-tumor activity through three main
mechanisms:
1. Direct Oncolytic Effect:
Oncolytic viruses can undergo specific replication within tumor cells, primarily due
to the tumor's specific genetic alterations that prevent the cell's signaling
pathways from sensing and blocking virus replication. Tumor interferon defects
prevent the regulation of the virus defense system, increasing sensitivity to virus
infection. By genetic modification, the virulence factors of oncolytic viruses can
be weakened or deleted, preventing virus replication in normal tissues while
retaining the ability to replicate within tumor cells and kill them.
2. Elicitation of Anti-Tumor Immune Responses:
Oncolytic virus infection of tumor cells can transform "cold" tumors into "hot"
tumors, thereby triggering local and systemic anti-tumor immune responses. Immune
suppressive factors in the tumor microenvironment, such as regulatory lymphocytes,
interleukin-10 (IL-10), and programmed death-ligand 1 (PD-L1), can protect tumors
from immune surveillance. Oncolytic viruses disrupt the existing tissue structure in
the tumor microenvironment and can reverse the immunosuppressive microenvironment,
transitioning it from immune suppression to immune activation. After oncolytic virus
infection of tumor cells, cell lysis occurs, releasing tumor-associated antigens,
activating dendritic cells, increasing the infiltration of cytotoxic T lymphocytes,
and recruiting other immune-related cells and molecules. This results in an increase
in tumor-specific immune responses, leading to the clearance of distant and
uninfected tumor cells.
3. Expression of Anti-Tumor Target Genes and Anti-Angiogenesis:
Through genetic engineering, oncolytic viruses can express target genes that have
anti-tumor effects, such as P53, GM-CSF, IL-12, IL-15, anti-PD-L1, etc., further
enhancing their anti-tumor effects. In addition, some oncolytic viruses can infect and
destroy the tumor's vascular system, inducing neutrophil infiltration, leading to
vascular collapse and tumor cell death.
Oncolytic viruses (OVs) can be categorized into DNA virus carriers and RNA virus carriers
based on the type of nucleic acid in their genomes. DNA viruses mainly include herpes
simplex virus (HSV), adenovirus (AdV), vaccinia virus (VV), and parvovirus H1; while RNA
viruses mainly include reovirus (RV), Coxsackievirus (CV), poliovirus (PV), measles virus
(MV), Newcastle disease virus (NDV), and vesicular stomatitis virus (VSV). Among them,
the five most commonly used oncolytic viruses in clinical research are adenovirus, HSV-1,
reovirus, vaccinia virus, and Newcastle disease virus.
To date, five oncolytic virus products have been approved for marketing globally. There
are hundreds of projects in clinical trial stages, especially in recent years, new
generations of oncolytic viruses developed and marketed or in clinical stages have shown
better safety and stronger anti-tumor capabilities.
Our project team has isolated and modified multiple strains of genetically engineered
oncolytic herpes viruses, selecting the best strains for in vivo and in vitro
pharmacological and safety evaluations. We have achieved anti-tumor effects superior to
currently approved oncolytic virus control drugs. This virus has been engineered to
delete virulence factors that are toxic to normal cells, and genetic engineering
modifications have been made at multiple genomic loci. It can selectively replicate in
tumor cells and can express recombinant bispecific antibodies at high levels. Compared to
existing oncolytic virus formulations, this virus demonstrates improved safety and
anti-tumor activity and holds great promise for clinical translation. In preliminary
studies, the project team has also demonstrated significant anti-tumor effects of
oncolytic adenovirus expressing this bispecific antibody. Therefore, in this clinical
trial, our project team plans to conduct clinical translational research using the
original strain based on proprietary intellectual property that has undergone genetic
engineering improvements.
The implementation of this project will provide a highly potential and hopeful clinical
treatment strategy for advanced cancer patients with no other treatment options. It will
also provide new ideas, strategies, and experimental evidence for the development of
oncolytic virus new drugs.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. Male or female patients: ≥18 years.
2. a)Patients with confirmed advanced squamous cell carcinoma of the head and neck
(including nasopharynx) who meet the following criteria: Patients who have failed
standard second-line treatment. Tumors that cannot be cured through local treatment
(surgery or definitive radiation therapy).
b)Patients with stage III malignant melanoma who are not eligible for surgical
resection, or patients with stage IV malignant melanoma, who have failed at least
two lines of standard treatment (including chemotherapy, immunotherapy or targeted
therapy).
c)Patients with locally unresectable or metastatic advanced soft tissue sarcomas,
who have failed prior systemic treatments.
3. ECOG performance status score: 0-1.
4. Expected survival ≥3 months.
5. Time since the last chemotherapy/radiotherapy/surgery is more than 28 days.
6. Adequate organ function, as defined by the following criteria within 14 days before
enrollment:
Hematology: Hemoglobin ≥90g/L (without blood transfusion in the last 14 days);
Neutrophil count >1.5×10^9/L; Platelet count ≥80×10^9/L.
Biochemistry: Total bilirubin ≤1.5×ULN (upper limit of normal); Alanine
aminotransferase (ALT) or aspartate aminotransferase (AST) ≤2.5×ULN; if there is
liver metastasis, ALT or AST ≤5×ULN; Estimated glomerular filtration rate ≥60ml/min
(Cockcroft-Gault formula).
Cardiac Doppler ultrasound assessment: Left ventricular ejection fraction (LVEF)
≥50%.
7. Patients with injectable lesions (those suitable for direct injection or injection
with the assistance of medical imaging), defined as follows: at least one injectable
lesion in the skin, mucous membrane, subcutaneous tissue, or lymph node with a
longest diameter ≥10 mm, or multiple injectable lesions with a total longest
diameter ≥10 mm
8. No continuing acute toxic effects of any prior radiotherapy, chemotherapy, or
surgical intervention, i.e., all such effects must have resolved to Common
Terminology Criteria for Adverse Events (CTCAE, Version 5.0) Grade 1.
9. Signed written informed consent Subjects must sign a written informed consent form
approved by the competent authority and the research institution and date it. The
informed consent form must be signed before any protocol-related procedures (not
part of the subject's routine medical care) are conducted.
Subjects must be willing and able to comply with the scheduled visits, treatment regimen,
laboratory tests, and other requirements of the study.
Exclusion Criteria:
1. Participated in another drug clinical trial within the past 4 weeks.
2. Tumor located near major blood vessels or the trachea.
3. Has poorly controlled clinical heart symptoms or diseases, such as NYHA class 2 or
higher heart failure, unstable angina, myocardial infarction within the past year,
clinically significant ventricular or supraventricular arrhythmias requiring
treatment or intervention.
4. For female subjects: pregnant or lactating women.
5. Persistent or active infections, including but not limited to: active pulmonary
tuberculosis, positive HIV (Human Immunodeficiency Virus) antibodies, positive HBsAg
(Hepatitis B Surface Antigen), positive HBcAb (Hepatitis B Core Antibody), and
positive HCV (Hepatitis C Virus) antibody test results.
1. Participants who are positive for HBsAg and/or HBcAb must also provide baseline
HBV DNA results and undergo HBV DNA monitoring during the treatment according
to the protocol.
2. Participants with HBV DNA results of 10^4 copies/ml or ≥ 2000 IU/mL and any of
the following conditions should be excluded: 1) positive results for HBsAg
and/or HBeAg; 2) positive results for HBcAb and negative results for all
others.
3. Patients with a positive HCV antibody test result are only ineligible for study
participation if their HCV RNA test result is positive..
6. Has a history of substance abuse that cannot be discontinued or has psychiatric
disorders.
7. Has any active autoimmune disease or a history of autoimmune disease, including but
not limited to uveitis, enteritis, pituitary inflammation, nephritis,
hyperthyroidism, hypothyroidism; subjects with vitiligo or childhood asthma that has
completely resolved in adulthood without the need for intervention may be included;
subjects with asthma requiring bronchodilators for medical intervention cannot be
included.
8. Patients who have used systemic corticosteroids (>10g/day of prednisone or an
equivalent dose) or other immunosuppressive drugs in the 4 weeks prior to the
initial administration of the study drug will be excluded.
9. Has a history of substance abuse or known medical, psychological, or social
conditions, such as a history of alcoholism or drug abuse.
10. Known allergy, hypersensitivity reaction, or intolerance to oncolytic virus research
(including any excipients). A history of severe allergies to any drugs, foods, or
vaccines, such as anaphylactic shock, angioedema, respiratory distress, purpura,
thrombocytopenic purpura, or localized allergic necrotizing reaction (Arthus
reaction), etc.
11. Female subjects with pregnancy plans during the screening period or male subjects
with partners who have pregnancy plans.
12. Has accompanying diseases judged by the investigator to be seriously harmful to
patient safety or affecting the patient's completion of the study.
13. Patients who have undergone major surgery other than diagnosis or have unhealed
wounds, ulcers, or fractures within the 28 days prior to the initial administration
of the investigational drug will be excluded. For patients with lesion rupture,
screening may be considered, and the eligibility will be jointly assessed by the
investigator and the sponsor, depending on the specific circumstances of the
rupture. The injection site should be as far away from the rupture site as possible,
and during the treatment period, rupture-related adverse events should not be
recorded as investigational drug-related adverse events.
14. During the course of the study, the use of drugs against HSV, including but not
limited to acyclovir, valacyclovir, penciclovir, famciclovir, ganciclovir,
foscarnet, and cidofovir, may be required.
15. Patients with episodes of oral herpes (cold sores) may present with small,
bead-like, tense vesicles on or around the lips during the initial outbreak,
typically measuring approximately 0.5 to 1.5 centimeters in size. These vesicles may
also appear in the nose, ear, or finger areas and are often associated with
significant pain. Recurrent oral herpes typically presents as ulcers above the
vermilion border of the lip (lip herpes) and occasionally as ulcers above the hard
palate mucosa.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
West China Hospital, Sichuan University
Address:
City:
Chengdu
Zip:
610041
Country:
China
Status:
Recruiting
Contact:
Last name:
Xingchen Peng
Phone:
+86 18980606753
Email:
pxx2014@scu.edu.cn
Start date:
October 15, 2023
Completion date:
October 15, 2025
Lead sponsor:
Agency:
West China Hospital
Agency class:
Other
Source:
West China Hospital
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06080984
