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 study treatment, including but not limited to hospitalization for complications of infection, bacteremia, or severe pneumonia
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
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
Other severe acute or chronic medical conditions defined per protocol