Recurrent or metastatic malignant solid tumors
Conditions
Interventions
VT1093 Single dose- group 1:Intratumoral injection-1X10^6 pfu
VT1093 Single dose- group 2:Intratumoral injection-1X10^7 pfu
VT1093 Single dose- group 3:Intratumoral injection-1X10^8 pfu
VT1093 Single dose- group 4:Intratumoral injection-5X10^8 pfu
VT1093 multi dose- group 1:3 times Intratumoral injection-1X10^7 pfu
VT1093 multi dose- group 2:3 times Intratumoral injection-1X10^8 pfu
VT1093 multi dose- group 3:3 times Intratumoral injection-5X10^8 pfu
Sponsors
Beijing Shijitan Hospital, Capital Medical University; Shanghai Pudong Hospital
Eligibility
Sex/Gender
All
Age
18 Years to 75 Years
Inclusion criteria
Inclusion criteria: 1. Subjects with a definite histological and/or cytological diagnosis of recurrent or metastatic malignant solid tumors; Head and neck squamous cell carcinoma, malignant melanoma, esophageal cancer, breast cancer, colon cancer, cervical cancer, etc. were preferentially selected; 2. failed by standard treatment or not suitable for standard treatment at this stage; 3. Age 18-75 years old, male or female; 4. General physical condition ECOG score 0 ~ 2 ; 5. More than 3 months' expected survival; 6. At least one measurable lesion (according to RECIST 1.1 criteria) that is suitable for intratumoral injection; 7. Serum antibodies against herpes simplex virus type I (HSV-1) were positive; 8. Subjects must have appropriate organ function, and laboratory tests during the screening period must meet the following requirements: (1) Absolute neutrophil count (ANC) >=1.5×10^9 /L, platelet (PLT)>= 80×10^9 /L, hemoglobin (Hb)>= 85g/L; (2) Serum creatinine (Cr), Urea (Urea)/urea nitrogen (BUN) within 1.5 times the upper limit of normal value; (3) Serum total bilirubin (TBIL) <= 2 times the upper limit of normal value; (4) Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) <= 2.5 times of the upper limit of normal value; Subjects with liver metastases do not exceed 5 times the upper limit of normal; (5) Activated partial thromboplastin time (APTT) and prothrombin time (PT) within 1.5 times the upper limit of normal value; 9. Eligible patients (male and female) who are fertile must agree to use a reliable contraceptive method (hormonal or barrier method or abstinence) with their partner during the trial period and for at least 180 days after the last dose; Female patients of childbearing age must have a negative urine pregnancy test within 7 days prior to enrollment; 10. The subjects signed the informed consent voluntarily, and the compliance was expected to be good.
Exclusion criteria
Exclusion criteria: 1. Patients who have previously been treated with anti-PD-1, anti-PD-L1, and anti-CTLA-4 antibodies have experienced any serious adverse reactions related to immunotherapy; 2. COVID-19 nucleic acid or antibody test is positive (except for COVID-19 vaccine injection); 3. Subjects with any severe and/or uncontrolled medical condition, including: (1) Poor control of hypertension (systolic blood pressure >=150 mmHg or diastolic blood pressure >=100mmHg); (2) have grade I or higher myocardial ischemia or myocardial infarction, arrhythmias (including QTc= 450ms for men, QTc>=470ms for women), and grade 2 congestive heart failure (NYHA); (3) Active or uncontrolled severe infection (>=CTCAE grade 2 infection); (4) Patients who have previously received organ transplantation, bone marrow transplantation (hematopoietic stem cell transplantation) and severe immune dysfunction; (5) Urine routine indicated urine protein >=++, and confirmed 24-hour urine protein quantity > 1.0 g; 4. Patients with a history of type I diabetes; 5. Serious abnormalities in thyroid and cortisol tests; Have an active, known, or suspected autoimmune disease that requires systemic treatment; 6. Patients with symptomatic primary brain or brain metastases; 7. Patients with prior severe pulmonary interstitial changes (as determined by the investigator); 8. Patients with active pulmonary tuberculosis and strong positive OT test; 9. Patients with active bleeding or severe coagulation dysfunction; 10. Subjects who have developed a second primary cancer within 3 years (excluding cured cervical carcinoma in situ, non-melanoma skin cancer, and superficial bladder tumors); 11. Anti-tumor therapy, including endocrine, chemotherapy, radiotherapy, targeted therapy, immunotherapy and anti-tumor Chinese medicine therapy, was performed 4 weeks before the first administration; For subjects receiving nitrosourea and mitomycin chemotherapy, discontinuation within 6 weeks; 12. Have received prophylactic or attenuated vaccines and therapeutic vaccines within 4 weeks before the first dose; 13. Toxicity has not returned to CTCAE level 0 or 1 after previous anti-tumor therapy; 14. Currently has active hepatitis B, active hepatitis C, immunodeficiency virus or other clinically significant active infection; 15. Patients who had received more than tertiary surgery or had unhealed surgical wounds in the 4 weeks prior to enrollment; 16. Receive anti-herpes simplex virus therapy within 4 weeks, such as acyclovir, ganciclovir, valaciclovir, adenosine arabine, etc.; 17. Participated in other clinical trials within four weeks before enrollment; 18. Pregnant and lactating women and those who have a family plan within six months (male or female); 19. The investigator determines that the subjects are not suitable to participate in this study for any reason.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Safety indicators: Vital signs;Safety indicators: Physical examination (Basic evaluation of weight, skin, lymph nodes, neck (including thyroid), lung, heart, abdomen, limbs, and nervous system);Safety indicators: Blood routine examination;Safety indicators: Blood coagulation function;Safety indicators: Routine urine test;Safety indicators: Stool routine (occult blood);Safety indicators: Biochemical laboratory of blood;Safety indicators: Analysis of T/B lymph cell sub-group;Safety indicators: Analysis of Cytokine;Safety indicators: Analysis of Lipase;Safety indicators: Thyroid function;Safety indicators: Cortisol test;Safety indicators: Urine pregnancy test for women of childbearing potential;Safety indicators: Electrocardiogram;Safety indicators: Echocardiography;Safety indicators: Pulmonary function test;Safety indicators: ECOG score;Safety indicators: adverse event monitoring; | — |
Secondary
| Measure | Time frame |
|---|---|
| Biological distribution and biological effect evaluation indicators: Number of blood VT1093 copies;Biological distribution and biological effect evaluation indicators: Number of urine VT1093 copies;Biological distribution and biological effect evaluation indicators: Blood PD-1 monoclonal antibody;Biological distribution and biological effect evaluation indicators: blood anti-PD-1 monoclonal antibody and blood anti-HSV-1 neutralizing antibody;Biological distribution and biological effect evaluation indicators: blood lymphocyte classification;Biological distribution and biological effect evaluation indicators: rheumatic antibody profiling (ANA, AMA);Biological distribution and biological effect evaluation indicators: immunoglobulin testing (IgG, IgM);Biological distribution and biological effect evaluation indicators: VT1093 activity of swab sampling on the injection area;Preliminary efficacy evaluation indicators: objecive response rate, ORR;Preliminary efficacy evaluation indicators: desease control rate, DCR; | — |
Countries
China
Contacts
Public ContactJun Ren
Beijing Shijitan Hospital, Capital Medical University; Shanghai Pudong Hospital
Outcome results
None listed