A Clinical Study of GO321 in Patients With Advanced Solid Tumors

The goal of this clinical trial is to learn about the safety and tolerability of GO321 recombinant oncolytic virus injection, and if GO321 recombinant oncolytic virus injection works to treat advanced solid tumors in adults whose cancers have progressed after standard-of-care therapy. It will also learn about the pharmacokinetic features, viral shedding, immunogenicity of GO321, immune markers, and genomic and proteomic changes in patients. The main questions it aims to answer are: What safety issues and tolerability limitations do participants experience when receiving GO321 via intratumoral or intracavitary injection? Does GO321 have preliminary anti-tumor efficacy against advanced solid tumors resistant to standard treatment? What changes take place in viral distribution, viral shedding, immunity, blood immune markers, tumor or blood genomics and proteomics after GO321 administration? Researchers will assess different doses and dosing schedules of GO321 given by intratumoral or intracavitary injection across two study phases to find a suitable administration dose and regimen and verify the study endpoints. Participants will: Receive either a single injection of GO321 at different dose levels (in Part 1) or repeated GO321 injections at the recommended Phase 2 dose (in Part 2) by intratumoral or intracavitary routes; Complete scheduled hospital visits to undergo laboratory tests, imaging examinations and biological sample collection; Have their safety indicators, anti-tumor response, viral parameters, immune indicators and molecular profiles tracked throughout the study.

Inclusion Criteria: * Age 18 years old and above, regardless of gender. * Histologically or cytologically confirmed advanced malignant solid tumors that are refractory to or have failed standard therapy (including disease progression and/or intolerance to toxicity), or for which no standard therapy is available. * For patients with malignant ascites secondary to malignant tumors (e.g., ovarian cancer, gastrointestinal solid malignancies) who are planned to receive intracavitary injection, the following criteria must be met: * a. Malignant ascites is determined by the investigator to be caused by cancer cell dissemination, and not complicated by ascites due to other etiologies; * b. Recurrence of ≥ Grade 2 ascites within 4 weeks after at least one prior local therapy (including paracentesis, intraperitoneal chemotherapy, peritoneovenous shunt, hyperthermic intraperitoneal chemotherapy, etc.); * c. Large-volume peritoneal effusion confirmed by computed tomography (CT) or ultrasound, with a clinical indication for local therapeutic intervention targeting the ascites. * Patients scheduled for intratumoral injection must meet the following requirements: At least one evaluable lesion confirmed by local imaging per RECIST v1.1 that is amenable to intratumoral injection. A lesion suitable for intratumoral injection (with or without CT/ultrasound guidance) is defined as a palpable mass or a mass visible by CT/ultrasound that can be injected under CT/ultrasound guidance, located in the skin, subcutaneous tissue, or deep-seated regions, with a longest diameter ≥ 1.0 cm (or short axis ≥ 1.5 cm if a lymph node), and deemed appropriate for intratumoral injection by the investigator. If the injection site has been previously irradiated, eligibility may be considered after discussion with the sponsor. * Eastern Cooperative Oncology Group (ECOG) score ≤2. * Expected survival time ≥3 months. * Study participants had adequate organ function at screening/baseline, and the laboratory indicators met the following criteria: * a. Hematopoietic system (no previous blood transfusion or hematopoietic stimulating factor therapy within 14 days) : absolute neutrophil count (ANC) ≥1.5E+09/L; Hemoglobin (Hgb) ≥90g/L; Platelet count (Plt) ≥75E+09/L. * b. Liver function: serum total bilirubin (TBIL) ≤1.5×ULN, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤3×ULN, with liver metastasis TBIL≤3×ULN, ALT and AST≤5×ULN; Serum albumin ≥2.8 g/dL (Subjects may receive albumin supplementation to meet these laboratory criteria). * c. Renal function: serum creatinine (Cr) ≤1.5×ULN or creatinine clearance (according to Cockroft-Gault formula) \>50mL/min. * d. Coagulation: international normalized ratio (INR) ≤1.5, activated partial thromboplastin time (APTT) ≤1.5×ULN. * Study participants were willing and able to comply with protocol requirements for the duration of the trial, including but not limited to receiving treatment, use effective contraception throughout trial participation and for 6 months after the last study drug administration, and undergoing regular follow-up and examinations. Exclusion Criteria: * Female participants who were pregnant or lactating. * Presence 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. * Adverse events from prior anti-tumor therapy have not recovered to Grade ≤ 1 per CTCAE v6.0, or to the levels specified in the inclusion/exclusion criteria (with the exception of alopecia, skin hyperpigmentation, or other toxicities deemed by the investigator to have no safety risk). Participants with chronic Grade 2 toxicity may be eligible after discussion with the sponsor, provided the toxicity is asymptomatic or adequately controlled with stable medications. * Received nitrosoureas or mitomycin C within 6 weeks prior to the first dose of the investigational product; received oral fluoropyrimidines or small-molecule targeted agents within 2 weeks or 5 half-lives (whichever is longer) prior to the first dose; received traditional Chinese herbal medicines or proprietary Chinese medicines with anti-tumor indications within 2 weeks prior to the first dose; received other systemic anti-tumor therapies, including chemotherapy, radiotherapy, biotherapy, endocrine therapy, immunotherapy, etc., within 3 weeks or 5 half-lives (whichever is shorter) prior to the first dose. * 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. * 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 \>10 mg/ 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. The following patients are NOT excluded: * a. Subjects with clinically stable autoimmune thyroid disease * b. Patients receiving topical/inhaled corticosteroids (ocular, intra-articular, intranasal formulations) * c. Short-course glucocorticoids (≤3 days) used prophylactically (e.g., contrast allergy prevention) * d. Patients receiving physiological hormone replacement doses. * Received allogeneic tissue or solid organ transplantation. * 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) \