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

Inclusion Criteria

• Histologically or cytologically documented Non-muscle Invasive Bladder Cancer (NMIBC)
• Patient with BCG-treated but unresponsive NMIBC (persistent or recurrent defined as tumor lesion present after prior response).
• Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0 to 2.
• Patients who are able to understand and sign the informed consent form.
• Age ≥ 18 years old
• Ability to comply with protocol
• Life expectancy >/=12 weeks
• Adequate hematologic and end-organ function per protocol
• For women of childbearing potential: Negative serum or urine pregnancy test at screening.
• For both male and female subjects: agreement to remain abstinent (refrain from heterosexual intercourse) or use highly effective contraceptive methods that result in a failure rate of <1% per year during the treatment period and for at least 30 days after the last dose of study drug.

Exclusion Criteria

• Evidence of locally advanced or metastatic bladder cancer (including current disease involving renal pelvis, ureter, or prostatic urethra).
• Evidence of muscle-invasive bladder cancer
• Evidence of extravesical bladder cancer
• Active central nervous system (CNS) metastases.
• Prior treatment with PD-L1 or PD-1 inhibitor.
• Prior radiation to bladder
• 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.
• Patient is considered a poor medical risk that would interfere with cooperation with the requirements of the study.
• 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.
• Patient has not recovered (i.e, to ≤Grade 1 or to baseline) from previous intravesical BCG or other anti-cancer therapy induced AEs.
• 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
• 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
• 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.

• History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins
• Known hypersensitivity to biopharmaceuticals produced in Chinese hamster ovary cells
• Allergy or hypersensitivity to components of the avelumab formulation
• History of autoimmune disease defined per protocol
• Prior allogeneic stem cell or solid organ transplantation
• Current use of immunosuppressive medication defined per protocol
• 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.

• Positive test for HIV
• 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.

• 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.

• Active infection requiring systemic therapy
• Severe infections within 4 weeks prior to the first dose of st