Cretostimogene Grenadenorepvec for Bladder Cancer

Recruiting at 58 trial locations

Overseen By Andy Darilek

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: CG Oncology, Inc.

Disqualifiers: Muscle-invasive cancer, Immunodeficiency, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

325 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called Cretostimogene Grenadenorepvec for individuals with a specific type of bladder cancer that hasn't spread to the muscle. The trial aims to assess the safety and effectiveness of this treatment when administered directly into the bladder in various ways, with some groups also receiving an additional drug, gemcitabine. Suitable candidates have high-risk bladder cancer that has not responded well to previous treatments, such as BCG therapy, and have recently had all visible tumors removed. As a Phase 2 trial, this research focuses on evaluating the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that cretostimogene grenadenorepvec is generally well-tolerated by patients. Studies indicate it is safe for individuals with non-muscle invasive bladder cancer and works effectively, with many patients experiencing complete and lasting results. When combined with gemcitabine, a chemotherapy drug, both treatments appear safe and manageable.

As this is a Phase 2 trial, earlier studies have already tested cretostimogene grenadenorepvec, providing some confidence in its safety. However, all treatments can have side effects, which may vary among individuals. Participants should discuss any concerns with the trial team. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about Cretostimogene Grenadenorepvec for bladder cancer because it uses a virus-based approach to deliver treatment directly to the cancer cells. Unlike conventional treatments like chemotherapy or surgery, this method involves injecting a genetically-modified virus into the bladder, which can potentially target and destroy cancer cells without harming healthy tissue. Additionally, some treatment arms combine this with gemcitabine, a chemotherapy drug, aiming to enhance effectiveness. This unique delivery method and combination therapy approach could offer new hope for patients with bladder cancer by providing a more targeted and potentially less toxic treatment option.

What evidence suggests that this trial's treatments could be effective for bladder cancer?

Research has shown that cretostimogene grenadenorepvec holds promise for treating high-risk non-muscle-invasive bladder cancer. In earlier studies, about 75.5% of patients achieved a complete response, meaning their cancer was undetectable after treatment. Among those who responded, 58% remained cancer-free for up to 24 months, indicating long-term effectiveness. The treatment also helped 84.5% of patients avoid major surgeries like bladder removal. In this trial, some participants will receive cretostimogene grenadenorepvec alone, while others will receive it with gemcitabine. When combined with gemcitabine, another cancer drug, the treatment showed a 2-year recurrence-free survival rate of 46%. This evidence suggests that cretostimogene grenadenorepvec, alone or with gemcitabine, could effectively manage this type of bladder cancer. ^{6 7 8 9 10}

Who Is on the Research Team?

Pat Keegan

Principal Investigator

CG Oncology

Are You a Good Fit for This Trial?

This trial is for adults with high-risk bladder cancer that hasn't invaded muscle. They should not have had BCG treatment or only up to 2 doses in the last 24 months, and their tumors must be mostly urothelial with less than half being a different subtype. All visible cancer should be removed recently.

Inclusion Criteria

My organs are functioning well.

My bladder cancer was confirmed by a doctor and I have never had BCG treatment.

I have bladder cancer and haven't had BCG treatment or only had 1-2 doses in the last 2 years.

Exclusion Criteria

Pregnant or breastfeeding

I have a weak immune system.

I have had a serious urinary tract condition in the last 2 years or any history of advanced urinary tract disease.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Induction Treatment

Cretostimogene and DDM are administered weekly for 6 weeks as an induction course

6 weeks

Reinduction Treatment

Reinduction course for patients with CIS and/or high-grade Ta disease at the 3-month evaluation

3 months

Maintenance Treatment

Maintenance treatment with three weekly treatments every three months during the first year, and every six months during the second year

2 years

Follow-up

Participants are monitored for disease status using urine cytology, cystoscopy, and other assessments every 3 months for the first 2 years, then every 6 months for a further 2 years

4 years

Optional Extension

Optional extension to the third year following the same six-month schedule as the second year

1 year

What Are the Treatments Tested in This Trial?

Interventions

• Cretostimogene Grenadenorepvec

Trial Overview

The study tests Cretostimogene Grenadenorepvec's safety and effectiveness against high-risk non-muscle-invasive bladder cancer (NMIBC). It's an open-label Phase 2 trial, meaning both researchers and participants know what treatment is given.

How Is the Trial Designed?

Group I: Experimental: Cohort CX, Arm 2 Experimental Treatment 1 Intervention

Cretostimogene (1 x 1012 vp) will be administered intravesically via an alternative instillation method for two consecutive weeks, followed by gemcitabine administered intravesically in the third week on a cyclic 2:1 visit schedule basis

Group II: Experimental: Cohort CX, Arm 1 Experimental Treatment 1 Intervention

At all treatment visits cretostimogene (1 x 1012 vp) will be administered intravesically via an alternative instillation method followed by gemcitabine instilled intravesically

Group III: Experimental: Cohort B, Arm 2 Experimental Treatment 1 Intervention

Cretostimogene (1 x 1012 vp) will be administered intravesically via an alternative instillation method.

Group IV: Experimental: Cohort B, Arm 1 Experimental Treatment 1 Intervention

Cretostimogene (1 x 1012 vp) will be administered intravesically via an alternative instillation method.

Group V: Experimental: Cohort A, Arm 3 Experimental Treatment 1 Intervention

Cretostimogene (1 x 1012 vp) will be administered intravesically via an alternative instillation method.

Group VI: Experimental: Cohort A, Arm 2 Experimental Treatment 1 Intervention

Cretostimogene (1 x 1012 vp) will be administered intravesically via an alternative instillation method.

Group VII: Experimental: Cohort A, Arm 1 Experimental Treatment 1 Intervention

Cretostimogene (1 x 1012 vp) will be administered intravesically via the current instillation method

Who Is Running the Clinical Trial?

CG Oncology, Inc.

Lead Sponsor

Trials

9

Recruited

900+

Published Research Related to This Trial

In a phase 1b clinical trial involving 9 patients with non-muscle invasive bladder cancer (NMIBC), the combination of intravesical N-803 and BCG showed promising results, with all participants remaining disease-free for 6 years after treatment.

The treatment was well-tolerated, with no dose-limiting toxicities and manageable adverse events, indicating a favorable safety profile for this combination therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety, Tolerability, and Long-Term Clinical Outcomes of an IL-15 analogue (N-803) Admixed with Bacillus Calmette-Guérin (BCG) for the Treatment of Bladder Cancer. Rosser, CJ., Tikhonenkov, S., Nix, JW., et al.[2022]

Antibody-drug conjugates (ADCs) like enfortumab vedotin and sacituzumab govitecan have shown significant efficacy in treating advanced urothelial carcinoma, with enfortumab vedotin being effective alone or in combination with pembrolizumab, and both having received FDA approval.

Common side effects of these treatments include rash and neuropathy for enfortumab vedotin, and myelosuppression and diarrhea for sacituzumab govitecan, highlighting the importance of monitoring patient safety during therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antibody-drug conjugates for urothelial carcinoma. Thomas, J., Sun, M., Getz, T., et al.[2023]

Novel intravesical therapies, including chemotherapeutic agents, immune checkpoint inhibitors, and gene therapies, show promise for treating non-muscle-invasive bladder cancer (NMIBC), although most evidence comes from single-arm trials with recurrent cases.

Innovative drug delivery methods, such as hyperthermic Mitomycin C and MMC hydrogel formulations, have shown encouraging results, highlighting the need for further randomized studies to compare these new treatments against current standards, especially due to ongoing BCG shortages.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Novel intravesical therapeutics in the treatment of non-muscle invasive bladder cancer: Horizon scanning. Ward, K., Kitchen, MO., Mathias, SJ., et al.[2022]

Enfortumab vedotin, an antibody-drug conjugate targeting Nectin-4, has shown promising results in treating advanced urothelial carcinoma that has progressed after chemotherapy or immunotherapy, leading to its expedited approval by the FDA.

The review highlights the growing number of therapies for advanced urothelial carcinoma, emphasizing the importance of understanding the mechanisms of action and safety profiles of these treatments, particularly enfortumab vedotin.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Current and Emerging Treatments for Urothelial Carcinoma: A Focus on Enfortumab Vedotin. Shafique, MA., Haseeb, A., Siddiq, MA., et al.[2023]

Enfortumab vedotin (EV) is an FDA-approved treatment for patients with treatment-refractory urothelial cancer, showing overall response rates of 40% to 52%, even in patients with poor prognosis due to visceral metastasis.

EV is generally well tolerated, especially in patients who cannot receive cisplatin, though it can cause manageable side effects like skin toxicity and peripheral neuropathy, which may limit dosage in some cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Targeted Treatment of Locally Advanced and Metastatic Urothelial Cancer: Enfortumab Vedotin in Context. Hoffman-Censits, J., Maldonado, L.[2022]

Citations

1.

ir.cgoncology.com

ir.cgoncology.com/news-releases/news-release-details/cretostimogene-grenadenorepvec-data-continues-demonstrate-best

Cretostimogene Grenadenorepvec Data Continues to ...

83 out of 110 patients (75.5%) achieved a complete response (CR) at any time in a Phase 3 study of cretostimogene monotherapy for high-risk BCG-unresponsive ...

2.

urotoday.com

urotoday.com/trials-in-progress/pivot-006-trial/videos/5131-phase-3-trial-results-for-intravesical-cretostimogene-grenadenorepvec-in-bladder-cancer-mark-tyson.html

Phase 3 Trial Results for Intravesical Cretostimogene ...

Among complete responders, 58% maintain durable responses at 24 months, suggesting potential long-term disease control with finite treatment ...

3.

cgoncology.com

cgoncology.com/cg-oncology-announces-bond-003-topline-results-aua-2025/

CG Oncology Announces Best-in-Disease Durability Data ...

Robust 24-month complete response rate of 42.3% by KM for cretostimogene monotherapy in BOND-003 Cohort C. 58.3% of patients showed durable complete responses ...

4.

onclive.com

onclive.com/view/cretostimogene-grenadenorepvec-produces-durable-crs-in-high-risk-bcg-unresponsive-nmibc

Cretostimogene Grenadenorepvec Produces Durable CRs ...

Additional Efficacy Data ... At 24 months, 97.3% of patients (n = 110) were free from progression to MIBC, and 84.5% avoided radical cystectomy.

5.

auajournals.org

auajournals.org/doi/10.1097/01.JU.0001111604.90306.91.02

BOND-003 COHORT C- PHASE 3, SINGLE-ARM STUDY ...

BOND-003 (NCT044552591) is a phase-3 study evaluating the efficacy and safety of cretostimogene in patients with HR BCG-UR NMIBC.

6.

cgoncology.com

cgoncology.com/cretostimogene-grenadenorepvec-data-continues-to-demonstrate-best-in-class-durability-of-response-as-well-as-consistent-and-compelling-safety-and-efficacy/

Cretostimogene Grenadenorepvec Data Continues to ...

Latest BOND-003 data show 75.5% of patients achieved a complete response at any time – – Median duration of response exceeds 28 months and ...

7.

cgoncology.com

cgoncology.com/science/

NMIBC | MIBC | Mechanism of Action of CG0070

Cretostimogene grenadenorepvec is an oncolytic immunotherapy with a dual mechanism of action that selectively replicates in and lyses cancer cells.

8.

urotoday.com

urotoday.com/conference-highlights/eau-2025/eau-2025-press-releases/159230-cretostimogene-grenadenorepvec-data-continues-to-demonstrate-best-in-class-durability-of-response-as-well-as-consistent-and-compelling-safety-and-efficacy.html

Cretostimogene Grenadenorepvec Data Continues to ...

“Cretostimogene's strong safety and efficacy profile, combined with its best-in-class durability, address an unmet need for my non-muscle invasive bladder ...

9.

ascopubs.org

ascopubs.org/doi/10.1200/JCO.2025.43.5_suppl.TPS902

Expanded access program of cretostimogene ...

Cretostimogene grenadenorepvec is an oncolytic immunotherapy with a dual mechanism of action. It selectively replicates and lyses bladder cancer ...

10.

clinicaltrials.gov

clinicaltrials.gov/study/NCT06111235

NCT06111235 | A Study of Adjuvant Cretostimogene ...

This is a Phase 3, open-label, randomized trial designed to evaluate the RFS of TURBT followed by cretostimogene grenadenorepvec versus TURBT followed by ...