CG0070 for Bladder Cancer

Overseen By Jake Silverman

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: H. Lee Moffitt Cancer Center and Research Institute

Must not be taking: Antivirals, Immunosuppressants

Disqualifiers: High-risk NMIBC, Muscle invasive cancer, Uncontrolled hypertension, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 12 weeks

20 Participants Needed

Trial Summary

What is the purpose of this trial?

Investigators will evaluate the safety of CG0070 for the treatment of patients with Intermediate-Risk Non-Muscle Invasive Bladder Cancer (IR NMIBC).

Will I have to stop taking my current medications?

The trial does not specify if you must stop all current medications, but you cannot use certain anti-viral medications and must be able to pause anti-platelet or anti-coagulant therapy for procedures. If you're on high-dose corticosteroids or certain other treatments, you may need to stop them before joining the trial.

What data supports the effectiveness of the drug CG0070 for bladder cancer?

The research highlights the potential of targeted therapies for bladder cancer, with antibody-drug conjugates like enfortumab vedotin and sacituzumab govitecan showing effectiveness in similar conditions. These drugs target specific proteins on cancer cells, which may suggest a promising approach for treatments like CG0070 that also aim to target cancer cells more precisely. ^{1 2 3 4 5}

How is the treatment CG0070 different from other bladder cancer treatments?

CG0070 is a unique treatment for bladder cancer because it is an oncolytic virus that specifically targets and kills cancer cells with a defective retinoblastoma pathway, unlike traditional therapies. It is administered directly into the bladder (intravesical infusion) and is particularly used for patients who do not respond to the standard BCG treatment. ^{6 7 8 9 10}

Research Team

Roger Li, MD

Principal Investigator

Moffitt Cancer Center

Eligibility Criteria

Inclusion Criteria

Willing to use barrier contraception during sexual activity for up to 6 weeks after each dose of CG0070

I can take care of myself and am up and about more than half of my waking hours.

My bladder cancer is confirmed to be a specific type and stage.

Exclusion Criteria

My bladder cancer is at a low risk of getting worse.

I have not had any cancer treatment in the last 4 weeks.

I have not had a heart attack or stroke in the last 6 months.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive CG0070 treatment after transurethral resection

12 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

24 months

Treatment Details

Interventions

• CG0070

Trial Overview This trial is focused on assessing the safety of a treatment called CG0070 for patients with Intermediate-Risk Non-Muscle Invasive Bladder Cancer (IR NMIBC).

Participant Groups

Group I: CG0070 Experimental Treatment 1 Intervention

CG0070 is a conditionally replicating oncolytic adenovirus (serotype 5) designed to preferentially replicate in and kill cancer cells.

Who Is Running the Clinical Trial?

H. Lee Moffitt Cancer Center and Research Institute

Lead Sponsor

Trials

576

Recruited

145,000+

Findings from Research

Immune checkpoint inhibitors have emerged as a promising alternative to traditional platinum-based chemotherapy for advanced urothelial cancer, showing better toxicity profiles and efficacy, although most patients still do not respond to these treatments.

There is a critical need for new therapeutic options and biomarkers to predict treatment responses, as ongoing clinical trials are exploring various combinations of therapies, including novel agents like enfortumab vedotin and erdafitinib, which have received breakthrough designation from the FDA.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Conceptual Framework for Therapeutic Development Beyond Anti-PD-1/PD-L1 in Urothelial Cancer. Grivas, P., Drakaki, A., Friedlander, TW., et al.[2019]

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]

Screening 17 bladder cancer cell lines in 3D culture using 652 investigational small molecules revealed that this method is more representative of in vivo drug responses compared to traditional 2D culture.

The study identified MEK inhibitors as a promising targeted therapy specifically for the basal subtype of bladder cancer, highlighting the potential of 3D drug screening to uncover effective treatment options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

MEK is a promising target in the basal subtype of bladder cancer. Merrill, NM., Vandecan, NM., Day, KC., et al.[2020]

A study analyzed the protein expression of various cancer targets in different subtypes of bladder cancer, revealing that a significant percentage of patients could be eligible for targeted therapies: 58.9% of small cell neuroendocrine carcinoma (SCC) patients, 33.5% of adenocarcinomas (AC) and urachal carcinomas (UrC) patients, and 79.3% of squamous-differentiated bladder cancers (Sq-BLCA) patients.

The research suggests that personalized treatment options based on biomarker status could improve therapeutic outcomes for patients with nonurothelial bladder cancer, as many could benefit from specific targeted therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of Therapeutic Targets in Histological Subtypes of Bladder Cancer. Wucherpfennig, S., Rose, M., Maurer, A., et al.[2021]

Urothelial carcinoma remains a significant health challenge, with advanced cases having a median overall survival of nearly 1 year despite being sensitive to chemotherapy, highlighting the urgent need for new treatment options.

Emerging therapies, including new cytostatic agents and targeted therapies such as anti-EGFR and PI3K/mTOR inhibitors, are currently being evaluated in clinical trials, indicating a shift towards more innovative treatment strategies for this cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Emerging therapies for urothelial cancer. Serrano, C., Morales, R., Suárez, C., et al.[2012]

CG0070 is an oncolytic adenovirus that specifically targets and kills cancer cells lacking the retinoblastoma (Rb) protein, making it a promising treatment for certain types of bladder cancer.

The study outlines standardized protocols for administering CG0070 intravesically, providing guidance for its use in patients with bladder cancer that does not respond to traditional BCG therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intravesical Infusion of Oncolytic Virus CG0070 in the Treatment of Bladder Cancer. Grandi, P., Darilek, A., Moscu, A., et al.[2023]

In a phase II trial involving 45 patients with high-grade non-muscle invasive bladder cancer (NMIBC) who were unresponsive to BCG treatment, intravesical CG0070 achieved a 47% complete response rate at 6 months, with a notable 58% response rate in patients with pure carcinoma in situ (CIS).

The treatment was generally well-tolerated, with common side effects including urinary bladder spasms and hematuria, but no severe (Grade IV/V) adverse events were reported, indicating a favorable safety profile for this therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An open label, single-arm, phase II multicenter study of the safety and efficacy of CG0070 oncolytic vector regimen in patients with BCG-unresponsive non-muscle-invasive bladder cancer: Interim results. Packiam, VT., Lamm, DL., Barocas, DA., et al.[2018]

In a study of 480 patients with intermediate- and high-risk non-muscle-invasive bladder cancer (NMIBC), those who switched to chemotherapy after discontinuing bacillus Calmette-Guérin (BCG) treatment had a significantly better three-year recurrence-free survival (RFS) rate compared to those who did not receive any further treatment.

The chemotherapy replacement group had a higher total number of instillations (14.9) compared to the pure BCG group (10.5), and multivariate analysis showed that the pure BCG group had more than double the risk of recurrence, highlighting the potential efficacy of chemotherapy as a replacement therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Replacement Instead of Discontinuation of Bacillus Calmette-Guérin Instillation in Non-Muscle-Invasive Bladder Cancer. Lin, PT., Hung, WK., Chang, YH., et al.[2023]

In a phase I/IIa trial involving eight patients with invasive bladder cancer, the intrabladder administration of AdCD40L gene therapy was found to be safe, with only minor side effects like transient local pain and some urinary tract infections, but no adverse events linked to the therapy itself.

The treatment successfully induced immune activation, as evidenced by increased T cell infiltration and elevated levels of the effector marker IFN-gamma in bladder biopsies, while also reducing the presence of malignant cells, suggesting potential efficacy in treating bladder cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

AdCD40L immunogene therapy for bladder carcinoma--the first phase I/IIa trial. Malmström, PU., Loskog, AS., Lindqvist, CA., et al.[2021]

In a study of 64 patients with high-risk superficial bladder cancer, bacillus Calmette-Guérin (BCG) treatment resulted in a significantly lower recurrence rate (28.1%) compared to gemcitabine (53.1%), indicating that BCG is more effective for this condition.

Gemcitabine was better tolerated than BCG, with fewer patients needing delayed treatment or withdrawal, suggesting it could be a suitable alternative for those who cannot tolerate BCG.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bacillus Calmette-Guérin versus gemcitabine for intravesical therapy in high-risk superficial bladder cancer: a randomised prospective study. Porena, M., Del Zingaro, M., Lazzeri, M., et al.[2022]

References

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

Conceptual Framework for Therapeutic Development Beyond Anti-PD-1/PD-L1 in Urothelial Cancer. [2019]

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

Antibody-drug conjugates for urothelial carcinoma. [2023]

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

MEK is a promising target in the basal subtype of bladder cancer. [2020]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Evaluation of Therapeutic Targets in Histological Subtypes of Bladder Cancer. [2021]

5. Netherlands pubmed.ncbi.nlm.nih.gov

Emerging therapies for urothelial cancer. [2012]

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

Intravesical Infusion of Oncolytic Virus CG0070 in the Treatment of Bladder Cancer. [2023]

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

An open label, single-arm, phase II multicenter study of the safety and efficacy of CG0070 oncolytic vector regimen in patients with BCG-unresponsive non-muscle-invasive bladder cancer: Interim results. [2018]

8. Switzerland pubmed.ncbi.nlm.nih.gov

Replacement Instead of Discontinuation of Bacillus Calmette-Guérin Instillation in Non-Muscle-Invasive Bladder Cancer. [2023]

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

AdCD40L immunogene therapy for bladder carcinoma--the first phase I/IIa trial. [2021]

10. Switzerland pubmed.ncbi.nlm.nih.gov

Bacillus Calmette-Guérin versus gemcitabine for intravesical therapy in high-risk superficial bladder cancer: a randomised prospective study. [2022]