A Study to Investigate the Safety, Tolerability, Pharmacokinetics, and Preliminary Efficacy of SIM0237 Alone or in Combination with BCG in NMIBC

Exclusion Criteria20

• • Subjects received TURBT or other surgical treatment for bladder lesions or pelvic radiotherapy or interventional therapy within 2 weeks prior to the first dose.
• Previous treatment with: a) IL-15 or IL-2; b) immune checkpoint inhibitors (such as anti-PD-1 or PD-L1 antibodies), ADCs, chemotherapies, oncolytic viruses, BCG or other anti-tumor treatments, unless there is clear evidence of disease persistence/recurrence/progression after the above treatments and beyond 4 weeks prior to the first dose; c) Chinese herbal medicine treatment beyond 2 weeks prior to the first dose is allowed; d) A single immediate instillation of chemotherapy within 4 weeks prior to the first dose is allowed; e) intravesical instillation of mucosal protective agents (e.g., sodium hyaluronate) are allowed.
• Subject is participating in an investigational drug or investigational device study.
• Subjects have not recovered from AEs caused by previous anti-tumor treatment.
• History/evidence of prior muscle-invasive, locally advanced, metastatic bladder cancer or upper urinary tract (kidney, renal pelvis, ureter) and prostatic urethral tumors; or evidence of Ta/T1/CIS urothelial transitional cell carcinoma outside the bladder (urethra, ureter, renal pelvis) during the screening period.
• Patients with other malignancies within 5 years before the first dose.
• Any active infection or urinary tract infection requiring systemic treatment by intravenous infusion within 2 weeks before the first dose.
• Subjects with clinically significant cardiovascular disease within 6 months before the first dose of study treatment.
• Known human immunodeficiency virus (HIV) infection or known acquired immunodeficiency syndrome (AIDS).
• Active or chronic hepatitis B or hepatitis C infection.
• Known or suspected active autoimmune diseases.
• Concurrent use of any other anticancer therapy or chronic use of systemic corticosteroids at immunosuppressive doses (more than 10 mg/day prednisone or equivalent).
• History of pneumonitis or interstitial lung disease or severe obstructive pulmonary disease that requires oral or intravenous steroids to help recover.
• Known to be allergic or intolerant to study drugs, monoclonal antibodies, excipients; or allergic or intolerant to BCG (only for subjects receiving combined BCG therapy)
• Subjects discontinued prior BCG treatment due to AEs such as toxemia, systemic infection, or urinary incontinence (only for subjects receiving combined BCG therapy).
• History of allogeneic organ transplantation or graft-versus-host disease.
• Any live vaccines within 4 weeks before the first dose.
• Known mental illness or substance abuse that would interfere with trial complies.
• Subject is pregnant or lactating, or is expected to become pregnant or parent a child during the planned study period.
• Other conditions that investigators consider inappropriate for inclusion.