Advanced refractory solid tumors
Conditions
Interventions
Interventional group:Local injection of GO306 recombinant oncolytic vaccinia virus injection (including intratumoral, intraperitoneal, or intrathecal injection, etc., the specific administration mode
Sponsors
Anhui Provincial Cancer Hospital
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Inclusion criteria
Inclusion criteria: 1. Age = 18 years, either gender. 2. Histologically or cytologically confirmed disease progression after or on standard therapy, such as: a. Subjects with head and neck squamous cell carcinoma who have received at least 2 or more lines of systemic therapy including platinum-based chemotherapy; b. Subjects with ovarian cancer who have received at least 2 or more lines of systemic therapy, and at least 1 of these, including platinum-containing therapy, is assessed as platinum-resistant or platinum-intolerant; c. Subjects with colorectal cancer who received at least 3 or more lines of systemic therapy; d. Subjects with primary hepatocellular carcinoma who have received at least 2 lines of therapy or other standard 2 lines of systemic therapy; e. Subjects with soft tissue sarcoma who have received at least 1 line of standard therapy; f. Subjects with pancreatic cancer who have received at least 1 line of standard therapy; Subjects with melanoma who have received at least 2 lines of standard therapy; g. or subjects with advanced malignant solid tumors for which no standard therapy is currently available or who are intolerant to chemotherapy. 3. Subjects with intratumoral injectable lesions (with or without CT/ultrasound guidance), defined as cutaneous, subcutaneous or deep masses that are palpable or visible by CT/ultrasound and can be injected under CT/ultrasound guidance, with long diameter = 1. 5cm (for lymph nodes, short axis = 1. 5cm), and are suitable for repeated intratumoral injection as judged by the investigator. The injection site should not be complicated with infection, ulceration, necrosis, cavity or other conditions that are not suitable for intratumoral injection in the opinion of the investigator, and should not be close to important structures or encapsulated, and the injection site has not undergone radiotherapy. 4. At least one evaluable lesion confirmed by local imaging according to RECIST v1.1 and eligible for intratumoral injection. 5, ECOG score of 0 or 1; Life expectancy = 3 months. 6. Subject has adequate organ function at baseline, and laboratory parameters meet the following criteria: a. Hematopoietic system (no transfusion or hematopoietic stimulating factor therapy within 14 days is required): Absolute neutrophil count (ANC) = 1.5 × 10 ^ 9/L; Hemoglobin (Hgb) = 90 g/L; Platelet count (Plt) = 100 × 10 ^ 9/L. b. Liver function: AST and ALT = 2.5 × ULN if the subject has no liver metastases; If subject has liver metastases, ALT and AST = 5 × ULN Total Bilirubin (TBIL) = 1.5 × ULN; For subjects with TBIL > 1.5 × ULN, direct bilirubin (DBIL) = 1.0 × ULN. c.Renal function: serum creatinine = 1.5 x ULN or creatinine clearance (by Cockroft-Gault formula) > 50 mL/min. d. Coagulation: International normalized ratio (INR) = 1. 5, activated partial thromboplastin time (APTT) = 1. 5 × ULN. 7. The subject has recovered from the adverse events of previous treatment to CTCAE v5.0 grade 1 or below, or grade 2, but the symptoms are stable and cannot be recovered to lower grade as judged by the investigator, and the safety of the subject's participation in this study is not affected, such as alopecia, skin hyperpigmentation, etc.
Exclusion criteria
Exclusion criteria: I. Exclusion criteria: 1. Patients with advanced malignant tumor who have the chance of being cured by radical treatment. 2. Presence of severe chronic or active infection: active hepatitis B (HbsAg positive, and the detection value of HBV DNA is greater than the upper limit of normal); Active hepatitis C (those with positive anti-HCV antibody are further tested positive for HCV RNA); Known history of immunodeficiency virus (HIV) disease or positive HIV antibody test; Other conditions requiring systemic anti-infective treatment within 4 weeks of first dose of study drug, including but not limited to hospitalization for infectious complications, bacteremia, severe pneumonia, or active tuberculosis. 3. Has a history of active autoimmune disease such as systemic lupus erythematosus, rheumatoid arthritis, vasculitis, etc., or is receiving long-term systemic steroids (> 10 mg/day of prednisone or equivalent) or any other form of immunosuppressive therapy within 14 days before the first dose of study drug. Exclusion of the following: clinically stable autoimmune thyroid disease; Treatment with topical and inhaled glucocorticoids such as ocular, intra-articular, intranasal, etc.; Short-term use of glucocorticoids (no more than 3 days) for prophylaxis (e.g., prevention of contrast allergy); Hormone replacement therapy in physiologic doses. 4. Received allogeneic tissue or solid organ transplantation. 5. Known other malignancy within the past 2 years that is progressing or requires active treatment (note: except subjects with basal cell carcinoma of the skin and squamous cell carcinoma of the skin who have received potentially curative treatment). 6. Evidence of clinically significant immunodeficiency, e.g., primary immunodeficiency states such as severe combined immunodeficiency (SCID); Combined opportunistic infections. 7. Anticoagulants or antiplatelet drugs are required and cannot be interrupted before intratumoral injection, including: aspirin that cannot be stopped within 7 days before injection; Coumadin that cannot be discontinued within 7 days prior to injection; Direct thrombin inhibitors (dabigatran) or direct factor Xa inhibitors (rivaroxaban, apixaban, and neixaban) that cannot be stopped within 4 days prior to injection; Low molecular weight heparin (LMWH) that cannot be discontinued within 24 hours prior to injection, unfractionated heparin (UFH) that cannot be discontinued more than 4 hours prior to injection. 8. History of serious skin disease requiring systemic treatment within 2 years before the first dose of study drug, such as eczema, atopic dermatitis, burns, seborrheic dermatitis, psoriasis, severe acne, etc. 9. Patients with active gastrointestinal bleeding or other gastrointestinal disease that is not suitable for enrollment as judged by the investigator. 10. History of severe cardiovascular and cerebrovascular disease, including but not limited to: congestive heart failure with New York Heart Association (NYHA) functional classification = II; Left ventricular ejection fraction (LVEF) 470 ms or prolonged QT syndrome; Acute coronary syndrome, aortic dissection, serious arrhythmia, stroke or other grade 3 or higher cardio-cerebrovascular events within 6 months prior to the first dose; Presence of uncontrolled hypertension (systolic blood pressure > 140 mmHg or diastolic blood pressure > 90 mmHg). Subjects with a history of hypertension were allowed to enroll in t
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Objective response rate;Progression free survival;Adverse event; | — |
Secondary
| Measure | Time frame |
|---|---|
| Serious adverse event;Overall survival(1 year,1-2years);Immunogenicity;Laboratory tests for biomarkers; | — |
Countries
China
Contacts
Public ContactLiu Hu
Anhui Provincial Cancer Hospital
Outcome results
None listed