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

PRIMARY OUTCOMES

Primary Outcome 1 - Measure:

Primary Outcome 1 - Timeframe: N/A

CONDITION

• Bladder Cancer

ELIGIBILITY

Inclusion Criteria:
1. Histologically or cytologically documented Non-muscle Invasive Bladder Cancer (NMIBC)

- 2. Patient with BCG-treated but unresponsive NMIBC (persistent or recurrent defined as tumor lesion present after prior response).

- 3. Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0 to 2.

- 4. Patients who are able to understand and sign the informed consent form.

- 5. Age ≥ 18 years old

- 6. Ability to comply with protocol

- 7. Life expectancy >/=12 weeks

- 8. Adequate hematologic and end-organ function per protocol

- 9. For women of childbearing potential: Negative serum or urine pregnancy test at screening.

- 10. 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:
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

Gender: All

Minimum Age: 18 Years

Maximum Age: N/A

Healthy Volunteers: No

OFFICIAL INFORMATION

Name: Kelly Stratton, MD

Role: Principal Investigator

Affiliation: Stephenson Cancer Center

Overall Contact

Name: N/A

Phone: N/A

Email: N/A

LOCATION