A Phase 1 Study of Intravesical VAX014 for Instillation in Subjects With Non-Muscle Invasive Bladder Cancer

Inclusion Criteria:

1. Signed, informed consent
2. Age 18 or more years
3. Pathologically confirmed low-grade Ta urothelial carcinoma (UC) of the urinary bladder
4. NMIBC with one solitary measurable tumor at the start of study, measuring ≥ 5 mm and ≤ 15 mm in greatest diameter (up to 4 additional low-grade Ta lesions, each measuring no more than 15 mm may be removed at screening provided a single lesion remains)
5. Treatment-naïve or failed one previous regimen of intravesical therapy (BCG or chemotherapy)
6. If recurrent disease, then more than 6 months from prior resection, more than 3 months from completion of last intravesical therapy with BCG, and more than 6 weeks from completion of last therapeutic intravesical therapy with chemotherapy
7. If previously treated, recovered from prior treatment-related toxicity to ≤ Grade 1
8. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 116
9. Absolute neutrophil count (ANC) ≥ 1,500/mm3
10. Platelet count ≥ 100,000/mm3
11. Total bilirubin ≤ 1.5 x upper limit of normal (ULN), or ≤ 3 x ULN in subjects with Gilberts disease
12. Serum creatinine ≤ 1.5 x ULN or creatinine clearance ≥ 30 mL/min
13. Serum aspartate transaminase (AST) and serum alanine transaminase (ALT) ≤ 2.5 x ULN
14. Willingness to participate in collection of pharmacokinetic samples
15. Women of childbearing potential must have a negative serum pregnancy test.
16. All subjects of childbearing potential must be willing to use effective contraception while on treatment and for 3 months after the last dose of VAX014

Exclusion Criteria:

1. Additional papillary disease at screening (in addition to the solitary low-grade Ta lesion detailed in the inclusion criteria) that

   1. Consist of 6 or more lesions
   2. Consists of any lesion with a maximal diameter of greater than 15 mm
2. Confirmed or suspected perforated bladder
3. History of difficult catheterization that in the opinion of the investigator will prevent administration of VAX014
4. Presence or history of any high-grade urothelial cancer (including CIS) or high-grade urine cytology
5. Intravesical chemo-or biological therapy within 6 months of first administration of VAX014
6. UC of the ureters or urethra
7. History of interstitial cystitis
8. History of radiation to the pelvis
9. History of vesicoureteral reflux or an indwelling urinary stent
10. Other known active cancer(s) likely to require treatment or interfere with study objectives over the next two (2) years
11. Active, uncontrolled bacterial, viral, or fungal infection(s) requiring systemic therapy
12. Known HIV, Hepatitis B, or Hepatitis C infection
13. Significant cardiovascular risk (e.g., coronary stenting within 8 weeks, myocardial infarction within 6 months)
14. Major surgery other than diagnostic surgery within 4 weeks of first administration of VAX014
15. Pregnant or currently breast-feeding
16. Psychiatric illness/social situations that would interfere with compliance with study requirements
17. Presence of any sessile appearing tumor suspected of being invasive or high-grade