Brief Title: CG0070 Combined With Nivolumab in Cisplatin Ineligible Patients With MIBC

PRIMARY OUTCOMES

Primary Outcome 1 - Measure:

Primary Outcome 1 - Timeframe: N/A

CONDITION

• Muscle-Invasive Bladder Carcinoma
• Bladder Cancer

ELIGIBILITY

Inclusion Criteria:
* Participants must have histologically confirmed MIBC (T2-T4a, N0-N1, M0 per American Joint Commission on Cancer [AJCC]) pure or mixed histology urothelial carcinoma. Clinical node- positive (N1) patients are eligible provided the lymph nodes (LNs) are within the planned surgical LN dissection template.

- * The initial TURBT that showed muscularis propria invasion should be within 90 days prior to beginning study therapy. Participants must have sufficient baseline tumor tissue from either initial or repeat TURBTs. The local site pathologist will be asked to estimate and record the rough approximate percentage of viable tumor in the TURBT sample (initial or repeat TURBT with highest tumor content) to document at least 20% viable tumor content prior to registration. This is to ensure adequate tissue is available to perform tumor infiltrating CD8+ T-cell assessment. (The actual CD8+ T cell analysis will be done by a Central Laboratory and will not be done prior to registration.)

- * Participants must be ineligible for cisplatin-based chemotherapy due to any of the following:
* Creatinine clearance (CrCl) < 60 mL/min (with ECOG Performance Status (PS) 0-1) - * Hearing impaired ≥ Grade 2 by CTCAE criteria - * Neuropathy ≥ Grade 2 by CTCAE criteria - * Heart failure NYHA ≥ III - * ECOG ≥ 2 - * Refusing to undergo cisplatin chemotherapy - * Participants must be medically fit for TURBT and radical cystectomy (RC) - * Age ≥ 18 years - * Ability to understand and willingness to sign IRB-approved informed consent - * Willing to provide tumor tissue, blood, and urine samples for research - * Adequate organ function as measured by the following criteria, obtained ≤ 4 weeks prior to registration:
* Absolute Neutrophil Count (ANC) ≥ 1000/mm3 (stable off growth factor within 4 weeks of first study drug administration)

- * Platelets ≥ 100,000/mm3

- * Hemoglobin ≥ 8 g/dL

- * Serum Creatinine Clearance ≥ 20 mL/min using the Cockcroft-Gault formula

- * ALT and AST ≤ 2.5x ULN

- * Total Bilirubin ≤ 1.5x ULN (in the absence of previously diagnosed Gilbert's disease)
Exclusion Criteria:
* Women who are pregnant or breastfeeding, since the effects of nivolumab and CG0070 on the fetus or breastfeeding child are unknown. All sexually active females of childbearing potential (not surgically sterilized and between menarche and 1 year post menopause) must have a blood test to rule out pregnancy within 4 weeks prior to registration.

- * Participant with local symptoms from bladder cancer, (e.g. gross hematuria, dysuria, etc.) who are deemed to be unable to complete the treatment protocol.

- * Participant with active or prior documented autoimmune disease within the past 2 years prior to Screening or other immunosuppressive agent within 14 days of study treatment. NOTE: Participant with well controlled type 1 diabetes mellitus, vitiligo, Graves disease, Hashimoto's disease, eczema, lichen simplex chronicus, or psoriasis not requiring systemic treatment (within the past 2 years prior to Screening) are not excluded

- * Participants who have concurrent upper urinary tract (i.e. ureter, renal pelvis) invasive urothelial carcinoma. Participants with history of non-invasive (Ta, T1, Tis) upper tract urothelial carcinoma that has been definitively treated with at least one post-treatment disease assessment (i.e. cytology, biopsy, imaging) that demonstrates no evidence of residual disease are eligible.

- * Participants who have another malignancy that could interfere with the evaluation of safety or efficacy of the study drugs. Participants with a prior malignancy will be allowed without Principle Investigator approval in the following circumstances:
* Not currently active and diagnosed at least 3 years prior to the date of registration.

- * Non-invasive diseases such as low risk cervical cancer or any cancer in situ.

- * Localized (early stage) cancer treated with curative intent (without evidence of recurrence and intent for further therapy), and in which no chemotherapy was indicated (e.g. low/intermediate risk prostate cancer, etc.). Participants with other malignancies not meeting these criteria must be discussed prior to registration.

- * Participants who have received any prior immune checkpoint inhibitor (i.e. anti-KIR, anti-PD-1, anti- PD-L1, anti-CTLA4 or other).

- * Participants who have undergone major surgery (e.g. intra-thoracic, intra-abdominal or intra-pelvic), open biopsy or significant traumatic injury or specific anti-cancer treatment ≤ 4 weeks prior to starting study drug, or patients who have had placement of vascular access device ≤ 1 week prior to starting study drug, or who have not recovered from side effects of such procedure or injury.

- * Participants who have clinically significant cardiac diseases deemed not fit for radical cystectomy, including any of the following:
* History or presence of serious uncontrolled ventricular arrhythmias.

- * Clinically significant resting bradycardia.

- * Any of the following within 3 months prior to starting study drug: severe/unstable angina, Congestive Heart Failure (CHF), Cerebrovascular Accident (CVA), Transient Ischemic Attack (TIA).

- * Uncontrolled hypertension defined by a SBP ≥ 180 mm Hg and/or DBP ≥ 100 mm Hg, with or without anti-hypertensive medication(s).

- * Participants who have history of chronic active liver disease or evidence of acute or chronic Hepatitis B Virus (HBV) or Hepatitis C (HCV).

- * Participants who have known diagnosis of human immunodeficiency virus (HIV) infection. Testing is not required in absence of clinical suspicion.

- * Participants who have known diagnosis of any condition (e.g. post-hematopoietic or solid organ transplant, pneumonitis, inflammatory bowel disease, etc.) that requires chronic immunosuppressive therapy which cannot be stopped for the duration of the clinical trial. Usage of non-steroidal anti-inflammatory medications (NSAIDS) for the treatment of osteoarthritis and uric acid synthesis inhibitors for the treatment of gout are permitted.

- * Participants with any serious and/or uncontrolled concurrent medical conditions (e.g. active or uncontrolled infection, uncontrolled diabetes) or psychiatric illness that could, in the investigator's opinion, cause unacceptable safety risks or potentially interfere with the completion of the treatment according to the protocol.

- * Participants who have used any live viral vaccine for prevention of infectious diseases within 4 weeks prior to study drug(s). 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.

- * Participants unwilling or unable to comply with the protocol.

- * Participants with a known allergy to any of the study medications, their analogues, or excipients in the various formulations of any agent.

- * Participants who participate in any other therapeutic clinical trials, including those with other investigational agents not included in this trial throughout the duration of this study.

- * Use of excluded antiviral medication that cannot be suspended at least 14 days prior and for 14 days after the administration of any CG0070 treatment throughout the duration of the trial.

Gender: All

Minimum Age: 18 Years

Maximum Age: N/A

Healthy Volunteers: No

OFFICIAL INFORMATION

Name: Roger Li, MD

Role: Principal Investigator

Affiliation: Moffitt Cancer Center

Overall Contact

Name: N/A

Phone: N/A

Email: N/A

LOCATION