A Vaccine (CG0070) for the Treatment of Intermediate Risk Non-muscle Invasive Bladder Cancer after Transurethral Resection

Inclusion Criteria

• Be ≥ 18 years of age (or legal age of majority in the jurisdiction) on day of signing informed consent
• Have Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2
• Have pathologically confirmed * Recurrent low-grade Ta * Solitary low-grade Ta > 3cm * Low-grade Ta multifocal * High-grade Ta ≤ 3cm
• Have all visible disease except a single “marker lesion” of approximately 0.3 – 1 cm diameter removed at baseline prior to initial CG0070 treatment (photographic documentation of lesion location and size must be conducted). “Marker lesion” must be clearly identifiable and assessable in the judgment of the investigator. “Marker lesion” location and size must be documented by the investigator (e.g., via photography and notes)
• Aspartate transaminase (AST), alanine aminotransferase (ALT) ≤ 2.5 x upper limit of normal (ULN)
• Total serum bilirubin ≤ 1.5 x ULN (OR direct bilirubin ≤ ULN for participants with total bilirubin levels > 1.5 x ULN)
• Absolute neutrophil count (ANC) ≥ 1,000 cells/mm^3
• Hemoglobin ≥ 8 g/dL or ≥ 4.96 mmol/L
• Platelet count ≥ 100,000 platelets/mm^3
• Serum creatinine ≤ 1.5 x ULN or creatinine clearance ≥ 30 mL/min for patient with creatinine levels > 1.5 institutional ULN according to Cockcroft-Gault formula
• Serum chemistries: Sodium, potassium, and calcium within normal limits (WNL) or grade 1
• International normalized ratio (INR) or prothrombin time (PT) ≤ 1.5 x ULN unless receiving anticoagulation therapy and INR or PT is within the therapeutic range of intended use of anticoagulants. (NOTE: patients must be able to suspend, based on local practice, anticoagulant and anti-platelet therapy for study specific biopsies and procedures)
• Willing to use barrier contraception during sexual activity, starting with day 1 for up to 6 weeks after each dose of CG0070
• Patients must be willing to comply with study mandated cystoscopies, urine cytology, CT urograms, biopsies, and other procedures (including transurethral resection of bladder tumor [TURBT] or other resection for all visible disease). Patients who withdraw consent for these procedures will be withdrawn from the trial

Exclusion Criteria

• Current or prior evidence of high-risk NMIBC defined as: * High grade (HG) T1 * Any recurrent HG (grade [G]3) Ta * HG Ta > 3 cm (or multifocal) * Any carcinoma in situ (CIS) * Any bacillus Calmette-Guerin (BCG) exposure in HG patient * Any variant histology * Any lymphatic invasion (LVI) * Any HG prostatic urethral involvement
• Disease that is unable to be completely resected
• Lack of marker lesion
• Low-risk NMIBC defined as: * Low grade solitary Ta less than or equal to 3cm * Papillary urothelial neoplasm of low malignant potential
• Has current or past history of muscle invasive (T2 or higher stage) or locally advanced (T3/T4, any N) or metastatic bladder cancer
• Has history of high grade or low grade urothelial carcinoma in the upper genitourinary tract (kidneys, renal collecting systems, ureters) or prostatic urethra (including CIS of the urethra) within 12 months of enrollment
• Has received systemic anti-cancer therapy, including investigational agents, within 4 weeks of day 1 NOTE: For participants who have entered the follow-up phase of an investigational study may participate if it has been 4 weeks after the last dose of the previous investigational agent
• Has any of the following within 6 months prior to starting study treatment: untreated myocardial infarction, untreated severe/unstable angina, coronary/peripheral artery bypass graft, cerebrovascular accident, pulmonary embolus, uncontrolled hypertension, or uncontrolled congestive heart failure that is deemed to be preventative from the patient completing study intervention and/or assessment
• Has used excluded anti-viral medication (e.g., interferon/peg-interferon, ribavirin, etc.) within 14 days of day 1 and that cannot be suspended throughout for at least 14 days prior to and after each treatment with CG0070. Please consult with sponsor to discuss any anti-viral that cannot be discontinued
• Has had prior treatment with any human adenovirus serotype 5 based therapy (e.g., ad-interferon or adstiladrin/instiladrin/nadofaragene firadenovec)
• Requires use of anti-platelet or anti-coagulant therapy that cannot be safely suspended for per protocol biopsies and other procedures as per standard of care
• Has significant immunodeficiency due to underlying illness (e.g., known HIV/AIDS). Note that HIV testing is not mandatory unless required by local health authorities
• Has received systemic immunosuppressive medication including high-dose corticosteroids (e.g., systemic corticosteroids > 10 mg prednisone or equivalent) within 28 days prior to day 1. NOTE: Patients must not be receiving doses of > 10 mg/day of prednisone or equivalent at the time of study entry or during the study and corticosteroids may not be used for premedication
• Has had an allogeneic tissue/solid organ transplant
• Has a known history of hepatitis B (defined as hepatitis B surface antigen [HBsAg] reactive) or known active hepatitis C virus (defined as hepatitis C virus [HCV] ribonucleic acid [RNA] [qualitative] is detected) infection Note that testing for hepatitis B and hepatitis C is not mandatory unless required by local health authorities
• Has received prior radiotherapy within 2 weeks of start of study treatment. Participants must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted for palliative radiation ( ≤ 2 weeks of radiotherapy) to non-central nervous system (CNS) disease
• Has a known additional malignancy that, in the opinion of the treating physician, may interfere with the study conduct or require on study treatment for the malignancy
• Has an active infection requiring systemic therapy (e.g., urinary tract infection or other active infection)
• Has received a live replication competent vaccine within 30 days prior to the first dose of study drug. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, BCG, and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (e.g., FluMist®) are live attenuated vaccines and are not allowed. NOTE: COVID-19 vaccination is allowed but please contact the sponsor if the patient has received, or plans to receive, live replication competent COVID-19 vaccination and document the date and type of COVID-19 vaccine received
• Has not recovered (i.e., to ≤ grade 1 or to baseline status) from adverse events (AEs) due to a previously administered agent or therapy NOTE: * Patients with ≤ grade 2 neuropathy or having any alopecia are an exception to this criterion and may qualify for the study * If patient received major surgery, they must be at least 4 weeks from surgery AND have recovered adequately from the toxicity and/or complications from the surgery prior to starting therapy * Patients receiving prior radiation must have recovered ( < grade 1) from any acute toxicity * Patients having irreversible but not clinically significant toxicity are eligible
• Has an illness, metabolic dysfunction, physical examination finding, or clinical laboratory finding that gives reasonable suspicion of a disease or condition that would contraindicate study treatment or that would limit compliance with study requirements
• Is pregnant, currently breastfeeding or intending to breastfeed, within the projected duration of the trial beginning at screening through 6 weeks after the last study treatment
• Cannot tolerate study-related biopsies, intravesical (IVE) administration, or 1-hour bladder hold of CG0070
• IVE therapy within 8 weeks prior to beginning study treatment with the exception of cytotoxic agents (e.g., mitomycin C, gemcitabine, doxorubicin, and epirubicin) when administered as a single instillation immediately following a TURBT procedure which is permitted up to 14 to 60 days prior to beginning study treatment