Avelumab Plus Bacille Calmette-Guerin (BCG) in Patients With Non-muscle Invasive Bladder Cancer

Exclusion Criteria

• •1. Evidence of locally advanced or metastatic bladder cancer (including current disease involving renal pelvis, ureter, or prostatic urethra).
• •2. Evidence of muscle-invasive bladder cancer
• •3. Evidence of extravesical bladder cancer
• •4. Active central nervous system (CNS) metastases.
• •5. Prior treatment with PD-L1 or PD-1 inhibitor.
• •6. Prior radiation to bladder
• •7. Known additional malignancy that required active treatment within the last 2 years. Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin.
• •8. Patient is considered a poor medical risk that would interfere with cooperation with the requirements of the study.
• •9. Patient has a condition or laboratory abnormality that might confound the study results, or interfere with the patient's participation for the full duration of the study treatment.
• •10. Patient has not recovered (i.e, to ≤Grade 1 or to baseline) from previous intravesical BCG or other anti-cancer therapy induced AEs.
• •11. Treatment with any approved anti-cancer therapy, including chemotherapy (systemic or intravesical), radiation therapy, or hormonal therapy within 3 weeks prior to the first dose of study treatment
• •12. Treatment with any other investigational agent or participation in another clinical study with therapeutic intent within 4 weeks prior to the first dose of study treatment
• •13. Pregnant or lactating, or intending to become pregnant during the study
• •a. Women who are not postmenopausal (≥ 12 months of non-therapy-induced amenorrhea) or surgically sterile must have a negative serum pregnancy test result within 14 days prior to the first dose of study treatment.
• •14. History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins
• •15. Known hypersensitivity to biopharmaceuticals produced in Chinese hamster ovary cells
• •16. Allergy or hypersensitivity to components of the avelumab formulation
• •17. History of autoimmune disease defined per protocol
• •18. Prior allogeneic stem cell or solid organ transplantation
• •19. Current use of immunosuppressive medication defined per protocol
• •20. History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening chest CT scan
• •a. History of radiation pneumonitis in the radiation field (fibrosis) is permitted.
• •21. Positive test for HIV
• •22. Active hepatitis B (positive hepatitis B surface antigen \[HBsAg\] test at screening);
• •a. Patients with past or resolved hepatitis B (HBV) infection (positive anti-hepatitis B core antigen \[anti-HBc\] antibody test) are eligible. HBV DNA must be obtained in these patients prior to the first dose of study treatment.
• •23. Active hepatitis C
• •a. Patients positive for hepatitis C virus (HCV) antibody are eligible only if polymerase chain reaction assay is negative for HCV RNA.
• •24. Active infection requiring systemic therapy
• •25. Severe infections within 4 weeks prior to the first dose of study treatment, including but not limited to hospitalization for complications of infection, bacteremia, or severe pneumonia
• •26. Significant cardiovascular disease, such as cerebral vascular accident/stroke (\< 6 months prior to enrollment), New York Heart Association cardiac disease (Class II or greater), myocardial infarction within the previous 6 months, unstable arrhythmias, or unstable angina
• •27. Administration of a live/attenuated vaccine within 4 weeks prior to the first dose of study treatment, within 5 months following the administration of the last dose of study drug, or anticipation that such a live/attenuated vaccine will be required during the study
• •28. Other severe acute or chronic medical conditions defined per protocol