Study of APL-1202 in Non-Muscle Invasive Bladder Cancer Patients Who Are Resistant to One Induction Course of BCG Treatment

Exclusion Criteria

• •1. Stage T2 or above urothelial carcinoma or urothelial carcinoma outside the bladder
• •2. Stage T1 NMIBC recurred at 3 months or shorter from the first dose of prior induction BCG course
• •3. Recurrent high-grade Ta/T1 disease within 6 months from the last dose of adequate BCG therapy
• •4. Previous systemic immunotherapy for bladder cancer
• •5. Prior major surgery (not Transurethral Resection of Bladder Tumor \[TURBT/Cystoscopy\]), radiation therapy, or systemic therapy within 8 weeks of starting the study treatment
• •6. National Cancer Institute (NCI) Common Toxicity Criteria for Adverse Events (CTCAE) Grade 3 hemorrhage within four weeks from the starting study treatment
• •7. Any of the following medical conditions within the six months prior to investigational drug administration: myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident or transient ischemic attack, or pulmonary embolism
• •8. Hypertension that cannot be controlled by medications
• •9. Optic nerve disorders or with a history of optic nerve disorders
• •10. Other severe acute or chronic medical or psychiatric condition, or laboratory abnormality that may increase the risk associated with study participation or investigational drug administration, or may interfere with the interpretation of study results in the judgment of the Investigator
• •11. Clinically meaningful allergic reactions or any known hypersensitivity or prior reaction to any of the formulation components in the investigational drug
• •12. Systemic treatment on any investigational clinical trial within 28 days (or 5 half-lives of that agent, whichever is greater) prior to enrollment
• •13. Concurrent treatment with immunosuppressive or immunomodulatory agents, including any systemic steroid (exception: inhaled or topically applied steroids, and acute and chronic standard dose nonsteroidal anti-inflammatory drugs (NSAIDs), are permitted). Use of a short course (i.e., ≤ 2 day) of a glucocorticoid is acceptable to prevent a reaction to the IV contrast used for: computed tomography (CT) scans
• •14. Immunosuppressive therapy, including: cyclosporine, anti-thymocyte globulin, or tacrolimus within three months of study entry
• •15. Concurrent treatment with strong inducers or inhibitors of CYP450 enzymes
• •16. Concurrent treatment with low therapeutic index drugs (such as methotrexate) that are renally cleared by OAT1- and OAT3-mediated transport
• •17. History of prior malignancy, except for adequately treated in situ cancer or basal cell or squamous cell skin cancer or other cancers (e.g. breast, prostate) for which the patient has been disease free and/or received curative therapy. Exclusion of patients described above will be at the discretion of the Sponsor.
• •18. Progressive or persistent viral or bacterial infection
• •19. All infections must be resolved, and the subject must remain afebrile for seven days without antibiotics prior to enrollment
• •20. Urinary tract infection, including particularly bladder infection, must be resolved prior to being placed on study
• •21. Unmanageable active gastric ulcer or inflammation of gastrointestinal (GI) tract
• •22. Gastric bleeding within last 6 months prior to enrollment
• •23. Anuria
• •24. Unable to take oral medication
• •25. Unwilling or unable to comply with the protocol or cooperate fully with the Investigator and site personnel
• •26. Unwilling to sign the informed consent