A Clinical Study of GO306 in Patients With Advanced Solid Tumors

Exclusion Criteria

• •Female subjects who were pregnant or lactating.
• •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.
• •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.
• •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 \>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.
• •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) \<50%.
• •* c. QT interval corrected with Fridericia's method (QTcF) \>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 allowed to participate if blood-pressure control below this criterion was achieved and maintained with antihypertensive treatment.
• •Patients with grade 3 or above bleeding events in the previous 6 months; Or patients with \> grade 2 bleeding, hemangioma/vascular malformation, tumor stroke, tumor invasion of blood vessels, active gastrointestinal ulcer, and esophageal varices, who were judged by the investigators to have a significant risk of bleeding.
• •A history of severe skin disease requiring systemic treatment within the previous 2 years, such as eczema, atopic dermatitis, burns, seborrheic dermatitis, psoriasis, severe acne, etc.
• •Patients with severe allergy or hypersensitivity reaction after using any drug or biological product in the past.
• •Anticoagulants or antiplatelet drugs should be used before intratumoral injection and should not be interrupted, including aspirin within 7 days before injection; Coumarin that cannot be stopped within 7 days before injection; Direct thrombin inhibitors (e.g., dabigatran) or direct factor Xa inhibitors (e.g., rivaroxaban, apixaban and endoixaban) that cannot be stopped within 4 days before injection; "Low-molecular-weight heparin (e.g., low-molecular-weight heparin \[LMWH\]), which cannot be discontinued within 24 hours before injection, and unfractionated heparin (e.g., unfractionated heparin \[UFH\]), which cannot be discontinued more than 4 hours before injection."
• •Use of systemic immunomodulatory drugs within 14 days before the first use of the investigational drug, including but not limited to thymosin, IL-2, IFN, etc.
• •Other circumstances requiring systemic anti-infective treatment within 4 weeks prior to the first administration of the investigational product, including but not limited to hospitalization for infectious complications, bacteremia, severe pneumonia, or active tuberculosis.
• •Within 4 weeks before the first use of the investigational drug: receiving other unmarketed investigational drugs or treatments, and receiving live vaccines or live attenuated vaccines.
• •Subjects who had undergone major surgery requiring hospitalization within 4 weeks before the first use of the investigational drug, or who were expected to undergo major surgery during the trial.
• •Concomitant use of sensitive substrate drugs metabolized by CYP450 enzymes with a narrow therapeutic window that cannot be stopped within the first 5 half-lives of the investigational drug is recommended after discussion with the sponsor.
• •Any known mental illness or substance abuse that may interfere with the subject's ability to cooperate with the trial.
• •According to the evaluation of the investigators, the treatment risks are high, including but not limited to the high risk of bleeding, possible damage to the surrounding important tissue structures, the risk of shock caused by dizzy with blood and needles, and the risk of aggravating local infection.
• •If the participant plans to participate in another clinical trial during the trial period, plans to leave the trial site, or otherwise is not suitable for participation in the trial as assessed by the investigator.