Solid tumors
Conditions
Interventions
stage 1:Phase 1: A total of 9-12 subjects are planned to be enrolled, and the dose setting of oncolytic virus injection and the results of this product's IIT study are divided into 3 dose gradients, s
Sponsors
The first affiliated hospital of anhui medical university
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Inclusion criteria
Inclusion criteria: 1. Age 18 years and above, gender is not limited. 2. Patients with advanced malignant solid tumors diagnosed histologically or cytologically, refractory or failed to standard treatment (including disease progression and/or intolerable toxic side effects), or for which no standard treatment was available, including but not limited to breast cancer, bladder urothelial carcinoma, colorectal cancer, renal cancer, ovarian epithelial carcinoma, and neuroendocrine tumors. Examples include: a. Histologically or cytologically confirmed unresectable or metastatic urothelial carcinoma of the bladder: Failure or intolerance to prior platinum-based chemotherapy and PD-1/PD-L1 inhibitor therapy for unresectable or metastatic disease, or for which no standard treatment options are available. b. Patients with histologically or cytologically confirmed recurrent ovarian cancer with malignant ascites: prior treatment with at least 1 prior line of platinum-based chemotherapy-based therapy for which no standard treatment regimen is available, and subjects with germline or somatic BRCA mutations who have failed or intolerant to PARP inhibitors; c. Histologically or cytologically confirmed unresectable or metastatic colorectal cancer with liver metastases: prior treatment based on oxaliplatin, fluorouracil, and irinotecan (if patient is MSI-H/ dMMR requires treatment with PD-1/PD-L1 inhibitors) failure or intolerance, or no standard treatment regimen available; d. Patients with histologically or cytologically confirmed unresectable or metastatic renal cancer: for unresectable or metastatic renal clear cell carcinoma, who have failed or are intolerant to prior TKI and PD-1/PD-L1 inhibitor therapy, or for which no standard treatment options are available. Histologically or cytologically confirmed locally advanced or metastatic triple-negative breast cancer: Failure or intolerance to at least first-line standard chemotherapy and the chemotherapy regimen must include a taxane (eg, paclitaxel, docetaxel), or no standard therapy regimen available. f. Patients with neuroendocrine tumors must meet one of the following criteria: (1) Histopathologically confirmed advanced (surgically unresectable locally advanced or distant metastases) Ki-67>=55% Patients with G3 NET and NEC (including mixed neuroendocrine-non-neuroendocrine tumors [at least 30% neuroendocrine cancer component], excluding small cell lung cancer and [SCLC] and Mecker cell carcinoma): Received at least first-line standard chemotherapy (EP or EC) Failure or intolerance, or no standard treatment options available. (2) Patients with histopathologically confirmed advanced (locally advanced or distant metastases that cannot be surgically resected) NET G3 and patients with lung and mediastinal atypical carcinoid tumors: have previously received at least second-line standard therapy failure or intolerance, and the treatment regimen must include CAPTEM regimen or no standard treatment regimen available. Histologically or cytologically confirmed diagnosis of advanced solid tumors (except above, e.g., soft tissue sarcoma, etc.): Documented disease progression or intolerance during or after prior standard therapy, or for which no standard treatment options are available. 3. Patients with ovarian cancer and gastrointestinal solid malignant tumors with malignant ascites who plan to inject intravascularly need to meet the following requirements: a. Malignant ascites is pathologically diagnosed as caused by the spread
Exclusion criteria
Exclusion criteria: 1.Female subjects who were pregnant or lactating. 2.Patients who had received a diagnosis of another malignancy within the previous 2 years, except for cancers with a low risk of metastasis and death (5-year survival rate, >90%), such as adequately treated basal-cell or squamous-cell skin cancer or carcinoma in situ of the cervix and other cancers in situ. 3.The adverse effects of previous antitumor treatment have not returned to CTCAE v5.0 grade 1, baseline or lower, or the level specified in the inclusion/exclusion criteria (except for alopecia, hyperpigmentation and other adverse events judged by the investigator as no safety risk). Subjects with chronic grade 2 toxicity were eligible after discussion with the sponsor if they were asymptomatic or adequately controlled with stable medications. 4.Antineoplastic therapy, including chemotherapy, radiotherapy, biotherapy, endocrine therapy, or immunotherapy, was received within 4 weeks or five half-lived periods (whichever was less) before the first use of the investigational drug, except for the following drugs: nitrosourea or mitomycin C within 6 weeks before the first use of the investigational drug; For oral fluorouracil and small molecule targeted drugs, 2 weeks before the first use of the investigational drug or within the 5 half-lives of the drug, whichever is longer; The Chinese herbal medicine or Chinese patent medicine with anti-tumor indication was within 2 weeks before the first use of the investigational drug. 5.Presence of any of the following infections or diseases: a. Active hepatitis B (HbsAg positive and/or HbcAb positive with an HBV DNA test value greater than the upper limit of normal); Active hepatitis C (anti-HCV antibody positive for further HCV RNA positive); b. a known history of immunodeficiency virus (HIV) disease or HIV antibody positive or active syphilis; c. evidence of clinically significant immunodeficiency such as a primary immunodeficiency state such as severe combined immunodeficiency (SCID); Opportunistic bacterial infection. 6.Have a history of active autoimmune disease requiring systemic therapy such as systemic lupus erythematosus, rheumatoid arthritis, vasculitis, etc., or have been receiving long-term systemic steroids (prednisone >10mg/ day or equivalent dose of the same drug) or any other form of immunosuppressive therapy within 14 days before the first use of the investigational drug. Patients with clinically stable autoimmune thyroid disease were excluded. The patients were treated with topical and inhaled corticosteroids, such as ocular, intra-articular, nasal, etc. Short-term use of glucocorticoids (not more than 3 days) for prophylaxis (e.g., to prevent contrast allergy); Physiological doses of hormone replacement therapy. 7.Received allogeneic tissue or solid organ transplantation. 8.A history of severe cardiovascular and cerebrovascular disease, including but not limited to: a. New York Heart Association (NYHA) class =II congestive heart failure; b. left ventricular ejection fraction (LVEF) 470 ms or syndrome of prolonged QT interval; d. Acute coronary syndrome, aortic dissection, major arrhythmia, stroke, or other grade 3 or higher cardiovascular and cerebrovascular events occurred within 6 months before the first dose of dose; e. Presence of uncontrolled hypertension (systolic BP, >150 mmHg or diastolic BP, >100 mmHg) Subjects with a history of hypertension were allow
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Dose Limiting Toxicity;Safety endpoint; | — |
Secondary
| Measure | Time frame |
|---|---|
| Pharmacodynamics/immunological indicators;Pharmacokinetics/viral shedding indicators;Efficacy endpoints;Immunogenicity indicators; | — |
Countries
China
Contacts
Public ContactWang Hua
The first affiliated hospital of anhui medical university
Outcome results
None listed