QUILT-3.032: A Multicenter Clinical Trial of Intravesical Bacillus Calmette-Guerin (BCG) in Combination With ALT-803 (N-803) in Patients With BCG Unresponsive High Grade Non-Muscle Invasive Bladder Cancer

Inclusion Criteria:

• Male or female patients 18 years of age or older

• Histologic confirmation of non-muscle invasive bladder cancer of the transitionalcell carcinoma high-grade subtype (mixed histology tumors allowed if transitionalcell histology is predominant histology).

• Histologically confirmed presence of BCG-unresponsive CIS (with or without Ta or T1disease) or histologically confirmed presence of BCG-unresponsive high-grade Ta orT1 disease.

• Absence of resectable disease after transurethral resection (TURBT) procedures (residual carcinoma in situ (CIS) acceptable; patients with T1 tumors must undergorepeat resection and biopsy [inclusive of muscularis propria] if initial biopsy didnot include muscularis propria). Patients with high-grade Ta and/or T1 diseaseshould have complete resection before study treatment.

• BCG-unresponsive disease as defined as: (a) Persistent or recurrent CIS (+/-recurrent Ta/T1 disease) within 12 months of receiving adequate BCG (at least fiveof six doses doses of an initial induction course plus either at least two of threedoses of maintenance therapy or at least two of six doses of a second inductioncourse); or (b) Recurrent high-grade Ta/T1 disease within 6 months of completion ofadequate BCG (at least five of six doses of an initial induction course plus eitherat least two of three doses of maintenance therapy or at least two of six doses of asecond induction course); or (c) T1 high-grade disease at the first evaluationfollowing an induction BCG course alone (at least five of six doses of an initialinduction course).

• Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2

• Voluntary written informed consent and HIPAA authorization and agree to comply withall protocol-specified procedures and follow-up evaluations

Exclusion Criteria:

• Recurrence of BCG unresponsive Ta/T1 disease (without presence of CIS) > 6 monthsafter last BCG instillation or BCG unresponsive CIS > 12 months after last BCGinstillation.

• Life expectancy <2 years

• Any of the following clinical laboratory values at the time of enrollment: (1)Absolute neutrophil count (ANC) <800/µL or (2) Platelets < 50,000/µL

• Liver function abnormalities as indicated by ongoing hepatic enzyme elevation (ASTor ALT) >2 times upper limit of normal (ULN)

• Renal insufficiency as indicated by a creatinine level >3 times ULN

• History of or evidence of muscle-invasive, locally advanced, metastatic and/orextravesical bladder cancer (inclusive of the prostatic urethra); or any othercancer within the past 5 years that is progressing or requires active treatment.Exceptions are adequately treated basal cell or squamous cell skin cancer that hasundergone potentially curative therapy or in situ cervical cancer; and adequatelytreated stage I or II cancer or stable prostate cancer from which the patient iscurrently in complete remission, and is under active surveillance or hormonecontrol.

• Symptomatic congestive heart failure (CHF), New York Heart Association (NYHA) ClassIII or IV heart failure or other clinical signs of severe cardiac dysfunction

• Severe/unstable angina pectoris, or myocardial infarction within 6 months prior tostudy entry

• History or evidence of uncontrollable central nervous system (CNS) disease

• Active systemic infection requiring parenteral antibiotic therapy. All priorinfections must have resolved following optimal therapy

• Concurrent febrile illness, active urinary tract infection, active tuberculosis, ahistory of hypotension or anaphylactic reactions

• Ongoing chronic systemic steroid therapy required (>10 mg oral prednisone daily orequivalent)

• Women who are pregnant or nursing. Female patients of childbearing potential musthave a negative pregnancy test and must adhere to using a medically acceptablemethod of birth control prior to screening and agree to continue its use during thestudy and for 30 days after the last dose of study drug, or be surgically sterilized (e.g., hysterectomy or tubal ligation). Women of childbearing potential are definedas any female who has experienced menarche and who is NOT permanently sterile orpostmenopausal. Postmenopausal is defined as 12 consecutive months with no menseswithout an alternative medical cause. Males must agree to use barrier methods ofbirth control while on study and for 90 days post last dose of study drug.

• Patients currently receiving investigational or commercial anti-cancer agents oranti-cancer therapies other than BCG, ALT-803 and supportive care therapies foractive disease.

• Concurrent use of other investigational agents (not including FDA authorized drugsfor the prevention and treatment of COVID-19).

• Other illness or condition, including laboratory abnormalities, which in the opinionof the Investigator would exclude the patient from participating in this study. Thisincludes, but is not limited to, serious medical conditions or psychiatric illnesslikely to interfere with participation in the study.