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
• •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