Cretostimogene Grenadenorepvec for Bladder Cancer

Recruiting at 45 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

Trial Summary

What is the purpose of this trial?

This is a Phase 2, Multi-Arm, Multi-Cohort, Open-Label Study to Evaluate the Safety and Efficacy of Cretostimogene Grenadenorepvec in Participants with High-Risk Non-Muscle-Invasive Bladder Cancer.

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.

What makes the drug Cretostimogene Grenadenorepvec (CG0070) unique for bladder cancer treatment?

Cretostimogene Grenadenorepvec (CG0070) is unique because it is a genetically modified virus designed to selectively target and kill bladder cancer cells, which is different from traditional chemotherapy or immunotherapy approaches. This targeted mechanism aims to reduce harm to healthy cells and potentially improve treatment outcomes. ^{1 2 3 4 5}

Research Team

Pat Keegan

Principal Investigator

CG Oncology

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

References

1. United States 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. [2022]

2. New Zealand pubmed.ncbi.nlm.nih.gov

Targeted Treatment of Locally Advanced and Metastatic Urothelial Cancer: Enfortumab Vedotin in Context. [2022]

3. Switzerland pubmed.ncbi.nlm.nih.gov

Novel intravesical therapeutics in the treatment of non-muscle invasive bladder cancer: Horizon scanning. [2022]

4. New Zealand pubmed.ncbi.nlm.nih.gov

Current and Emerging Treatments for Urothelial Carcinoma: A Focus on Enfortumab Vedotin. [2023]

5. United States pubmed.ncbi.nlm.nih.gov

Antibody-drug conjugates for urothelial carcinoma. [2023]