Study of CG0070 Combined With Nivolumab in Cisplatin Ineligible Patients With MIBC

NCT04610671 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: MCC-20575
• Study Type: interventional
• Target: 21
• Locations: 1 country
• Sites: 1

Brief Summary

Investigators will evaluate the safety and efficacy of combination neoadjuvant therapy using intravesical CG0070 and IV Nivolumab in cisplatin ineligible patients with Muscle Invasive Bladder Cancer (MIBC).

Conditions

Muscle-Invasive Bladder Carcinoma; Bladder Cancer

Keywords

Bladder

Outcome Measures

Primary Outcomes (1)

• Incidence of Treatment-Emergent Adverse Events

  Adverse events Grade 3 or higher will be graded according to the NC Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0

  Up to 24 months after start of treatment

Secondary Outcomes (1)

• Change in PD-L1 expression on tumor and immune cells

  Up to 24 months after start of treatment

Other Outcomes (1)

• Changes in intraepithelial CD8+ T cell density

  Up to 24 months after start of treatment

Study Arms (1)

Participants Receiving CG0070 & Nivolumab

EXPERIMENTAL

Both CG0070 (x 6 instillations) and nivolumab (x 2 doses) will be administered at their single-agent dose and schedule.

Drug: CG0070; Drug: Nivolumab

Interventions

CG0070 DRUG

CG0070 will be administered at a dose of 1x10\^12 vp intravesically following a sequence of bladder washes with 5% DDM and normal saline.

Participants Receiving CG0070 & Nivolumab

Nivolumab DRUG

Two neoadjuvant doses of nivolumab 480 mg Q4W (every 4 weeks) for 2 doses (week 2 and 6)

Participants Receiving CG0070 & Nivolumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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).

Sponsors & Collaborators

• H. Lee Moffitt Cancer Center and Research Institute: lead
• CG Oncology, Inc.: collaborator
• Richard M. Shulze Family Foundation: collaborator

Study Sites (1)

Moffitt Cancer Center

Tampa, Florida, 33612, United States

Location

Related Publications (1)

• Li R, Villa NY, Yu X, Johnson JO, Borjas G, Dhillon J, Moran-Segura CM, Kim Y, Francis N, Dorman D, Powers JJ, Sexton WJ, Spiess PE, Poch MA, Zemp L, Gilbert SM, Zhang J, Pow-Sang JM, Anderson ARA, Li T, Wang X, Grass GD, Burke JM, Dinney CPN, Rodriguez PC, Jain RK, Mule JJ, Conejo-Garcia JR. Oncolytic immunotherapy with nivolumab in muscle-invasive bladder cancer: a phase 1b trial. Nat Med. 2025 Jan;31(1):176-188. doi: 10.1038/s41591-024-03324-9. Epub 2024 Nov 9.

  PMID: 39521884 RESULT

MeSH Terms

Conditions

Urinary Bladder Neoplasms

Interventions

Nivolumab

Condition Hierarchy (Ancestors)

Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Urinary Bladder Diseases; Urologic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Roger Li, MD

  Moffitt Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 26, 2020
• First Posted: October 30, 2020
• Study Start: October 26, 2020
• Primary Completion: July 25, 2024
• Study Completion: July 25, 2024
• Last Updated: February 27, 2026

Record last verified: 2026-02

Locations

US (1)