Clinical Trials

Key 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 (WHO grading system employed for tumor grading) (Compérat 2019) BCG unresponsive CIS. Patients with BCG unresponsive CIS are those unlikely to benefit from, and who will not be receiving, further intravesical BCG. There is no maximum limit to the amount of prior BCG treatment, but maintenance BCG should be administered on a schedule consistent with standard induction-maintenance protocols (e.g., BCG weekly x 6 then weekly x 3 weeks administered at Months 3, 6, 12, 18, 24, and 36). Specifically, the definition of BCG unresponsive CIS will also require the following:
  • Pathologically confirmed relapsed or persistent CIS (with or without TaHG or T1 disease) within 12 months of completion (last dose) of adequate BCG treatment for HGUC (e.g., CIS, TaHG, T1, or a combination of these HGUC pathologies);
  • Completion of qualifying BCG treatment (e.g., “5+2” minimum exposure) within 12 months of the initial qualifying dose of BCG (e.g., induction and initial maintenance or re-induction cycle must be completed over no more than a 12-month period of time);
  • Pathological confirmation of BCG unresponsive CIS within 8 weeks of study enrollment;
  • CIS specimen must be predominantly urothelial (transitional cell) and have less than 50% variant (e.g., sarcomatoid, squamous etc. component) histology;
  • No maximum limit to the amount of BCG administered but maintenance BCG should be administered on a schedule consistent with the SWOG 8507 regimen (Lamm 2000).
• Have all Ta and/or T1 disease resected and all CIS resected or fulgurated, as feasible, prior to study treatment (e.g., prior to Day 1 treatment).
  • NOTE: T1 disease resection site must have biopsy evaluation of the prior resection site 2–8 weeks prior to initial study treatment.
• Received prior adequate BCG therapy defined as at least one of the following (“5+2” minimum exposure; all 7 qualifying doses must be greater than or equal to one third [1/3] of full dose BCG):
  • At least 5 of 6 doses of an initial induction course (adequate induction) plus at least 2 of 3 doses of maintenance therapy; OR
  • At least 5 of 6 doses of an initial induction course (adequate induction) plus at least 2 of 6 doses of a second induction course;
  • The “5+2” minimum BCG treatment must be completed within 12 months of the initial qualifying BCG induction dose.
  • NOTE: Past qualifying “adequate BCG” must be clearly documented including dates of BCG treatment and pathological recurrence or persistence within 12 months of last dose of BCG. Please contact CG Oncology if there are questions.
• Ineligible to receive radical cystectomy (medically unfit) or refusal of radical cystectomy according to Investigator assessment.
• Demonstrate adequate organ function, defined as:
  • Aspartate transaminase (AST), alanine aminotransferase (ALT) ≤ 2.5 × upper limit of normal (ULN);
  • Total serum bilirubin ≤ 1.5 × ULN (OR direct bilirubin ≤ ULN for participants with total bilirubin levels > 1.5 × 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 × ULN or glomerular filtration rate (GFR) ≥ 30 mL/min/1.73 m^2 for patients with creatinine levels > 1.5 institutional ULN according to the 2021 Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) creatinine equation;
  • Serum chemistries: sodium, potassium, and calcium within normal limits (WNL) or Grade 1.
  • International normalized ratio (INR) or prothrombin time (PT) ≤ 1.5 × 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, as outlined in Section 8.C, during sexual activity, starting at least 30 days prior to Day 1 through 6 weeks after the last dose of CG0070.
• Patients must be willing to comply with study mandated cystoscopies, urine cytology, urograms, biopsies, and other procedures (including TURBT or other resection for all Ta/T1 disease) for the duration of the study. Patients who withdraw consent for these procedures will be withdrawn from the trial.

Exclusion Criteria:

• Has current or past history of muscle invasive (T2 or higher stage) or locally advanced (T3/T4, any N) or metastatic bladder cancer.
• Any HGUC as T1, TaHG, or CIS in the upper. genitourinary tract or prostatic urethra (including CIS of the urethra) within 24 months prior to enrollment OR any history of T2 or higher stage urothelial carcinoma in the upper genitourinary tract (kidneys, renal collecting systems, ureters).
• Has received systemic anti-cancer therapy, including investigational agents, within 4 weeks of Day 1.
  • NOTE: Participants who have entered the follow-up phase of an investigational study may participate as long as it has been 4 weeks after the last dose of the previous investigational agent.
• Has had prior systemic treatment (with the exception of checkpoint inhibitor therapy), radiation therapy, or surgery for bladder cancer other than TURBT or bladder biopsies.
• Has had prior treatment with any human adenovirus serotype 5 based therapy (e.g., Adinterferon or Adstiladrin).
• Has any of the following within the 6 months prior to starting study treatment: myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft, cerebrovascular accident, pulmonary embolus, uncontrolled hypertension, or uncontrolled congestive heart failure.
• 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.
• Requires use of anti-platelet or anti-coagulant therapy that cannot be safely suspended for per protocol biopsies as per standard of care.
• Has significant immunodeficiency due to underlying illness (e.g., known HIV/AIDS)
• Has received systemic immunosuppressive medication including high-dose corticosteroids (e.g., systemic corticosteroids >10 mg prednisone or equivalent), within 4 weeks 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.
  • NOTE: Patients with contrast dye allergies may be given 1–3 dose(s) of a systemic steroid in order to complete a contrast-enhanced CT urogram for trial purposes. A 14-day minimum separation of the steroid dose and CG0070 dose must occur.
• Has had prior organ or allogenic stem cell transplant.
• Has known active Hepatitis B (defined as HBsAg reactive) or known active Hepatitis C virus (defined as HCV RNA [qualitative] is detected) infection. Patients with active acute or active chronic Hepatitis B or C, who take medications with anti-Hepatitis B or C activity are ineligible. Patients who have evidence of hepatic decompensation or cirrhosis on physical exam, laboratory, pathologic or radiographic testing also are ineligible. Patients with inactive chronic Hepatitis B infection (asymptomatic healthy carriers) who meet the trial-defined laboratory parameters are eligible for trial entry.
  • NOTE: No testing for Hepatitis B and Hepatitis C is required unless mandated by a local health authority.
• Has current or prior pelvic (including the bladder) external beam radiotherapy within 2 weeks of entry Has a history of another malignancy within 3 years except the following:
  • Localized, low-risk, prostate cancer (e.g., stage ≤ T2b, Gleason score ≤ 7) treated with curative intent and without prostate-specific antigen recurrence;
  • Low risk prostate cancer (e.g., stage T1/T2a, Gleason score ≤ 7, and prostate-specific antigen ≤ 10 ng/mL) who are treatment naïve and undergoing active surveillance;
  • Cancers with negligible risk of metastasis or death (e.g., risk of death or metastasis <5% at 5 years) that have been treated with curative intent and no evidence of recurrence or metastasis (e.g., adequately treated CIS of the cervix, basal or squamous cell skin cancer, or ductal CIS of the breast).
• Has an active infection requiring systemic therapy (e.g., urinary tract infection or other active infection).
• Has had active autoimmune or inflammatory disease requiring systemic treatment within 4 weeks of Day 1 (i.e., with use of disease modifying agents, corticosteroids, or immunemodulating drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered an excluded form of systemic treatment and is allowed.
• 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, 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 14 or more days prior to beginning study treatment.
• Has received a live 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 CG Oncology if the patient has received or plans to receive live COVID-19 vaccination and document the date and type of COVID-19 vaccine received.

Note: Other protocol defined Inclusion/Exclusion Criteria may apply.

Eligibility last updated 8/29/23. Questions regarding updates should be directed to the study team contact.