CG0070 for Bladder Cancer

(BOND-003 Trial)

Recruiting at 88 trial locations

Overseen By JoAnn Horn

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: CG Oncology, Inc.

Must not be taking: Systemic anti-cancer therapy

Disqualifiers: Muscle invasive cancer, Metastatic cancer, Uncontrolled hypertension, others

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

Compensation: Varies

Number of Visits: 6

Duration: 36 months

190 Participants Needed

Trial Summary

What is the purpose of this trial?

This is a Phase 3, open-label, single arm trial designed to evaluate Cretostimogene patients with NMIBC who have failed prior BCG therapy. Up to approximately 115 CIS bladder cancer patients with or without HG Ta or HG T1 papillary disease will be enrolled under the original protocol through Amendment 4, which will comprise Cohort C. Cohort C is closed to enrollment. Under Amendment 5-1, Cohort P was added to enroll up to 70 patients with HG Ta/T1 papillary bladder cancer. Under Amendment 6, the target number of patients enrolled in Cohort P was increased to 75. Cohort P is open to enrollment Cohort C and Cohort P will be analyzed and reported separately. Patients will have had to fail prior BCG therapy which is defined as having persistent or recurrent disease within 12 months (Cohort C) or 6 months (Cohort P) following the completion of adequate BCG therapy for HGUC

Will I have to stop taking my current medications?

The trial protocol does not specify whether you need to stop taking your current medications. However, it mentions that you should not have received systemic anti-cancer therapy within 4 weeks of starting the trial, and certain intravesical therapies are restricted close to the trial start date.

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

The research highlights the potential of targeted therapies for bladder cancer, with various drugs showing promise based on specific biomarkers. While CG0070 is not directly mentioned, the study of antibody-drug conjugates and other targeted therapies suggests that personalized approaches, like CG0070, could be effective for certain patients with bladder cancer. ^{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 Bacillus Calmette-Guerin (BCG) treatment. ^{6 7 8 9 10}

Research Team

CG Oncology

Principal Investigator

CG Oncology

Eligibility Criteria

This trial is for adults with high-risk non-muscle invasive bladder cancer that hasn't responded to BCG therapy. Participants should be in fair to good physical condition (ECOG 0-2), not eligible or unwilling to undergo radical cystectomy, and have proper organ function. Those with muscle-invasive, advanced, or metastatic bladder cancer, other malignancies in the urinary tract, recent systemic anti-cancer treatments, immune deficiencies including HIV or past organ transplants are excluded.

Inclusion Criteria

I have completed the recommended BCG therapy.

My organs are working well.

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

Exclusion Criteria

You currently have an autoimmune disease that is not under control.

I haven't had any cancer treatment or been in a trial for new treatments in the last 4 weeks.

I have a weakened immune system due to long-term steroid use, HIV, or an organ transplant.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Cretostimogene is administered weekly for 6 weeks. If recurrence occurs at Week 13, a second induction of 6 weekly treatments is given. If no recurrence, 3 weekly treatments every 12 weeks through Week 51, then every 6 months through Month 36.

36 months

Weekly visits for initial 6 weeks, then every 12 weeks, and every 6 months

Follow-up

Participants are monitored for safety and effectiveness after treatment completion

12 months

Extension

Participants receive additional treatments every 6 months starting at Weeks 73, 74, and 75 through Week 159 if no tumor recurrence

36 months

Treatment Details

Interventions

• CG0070

Trial Overview The study tests CG0070 given directly into the bladder of patients who haven't responded to BCG treatment for their bladder cancer. It aims to see how effective this approach is. The intervention involves a compound called n-dodecyl-B-D-maltoside alongside CG0070 as part of the treatment process.

Participant Groups

Group I: Cohort P(Japan and United States Only) :Open to Enrollment Experimental Treatment 2 Interventions

HG Ta/T1 papillary disease bladder cancer patients. In Cohort P, cretostimogene will be administered at a dose of 1 × 1012vp IVE following instillation of 5% DDM. Cretostimogene will be administered every week for 6 treatments on Weeks 1, 2, 3, 4, 5, and 6. If the patient has recurrence at Week 13 or any timepoint, the patient will receive a second induction of 6 weekly treatments (Weeks 13, 14, 15, 16, 17, and 18.). If the tumor has not returned they will receive 3 weekly treatments every 12 weeks (approximately 3 months) starting Weeks 13, 14, and 15 through Week 51 (approximately 12 months), and then every 6 months starting at Weeks 73, 74, and 75 (approximately 18 months) through Month 36.

Group II: Cohort C(All Countries):Enrollment Closed Experimental Treatment 2 Interventions

Patients with CIS with or without HG Ta/T1 papillary disease. Cretostimogene will be administered intravesically following a series of bladder washes with 5% DDM and normal saline. Cretostimogene will be administered weekly x 6 on Weeks 1, 2, 3, 4, 5, and 6. If the patient has disease recurrence at Week 13, they will receive another cycle of 6 weekly treatments. If there is no disease present at Week 13 then the patient will receive 3 weekly treatments. Cohort C(All Countries):Beginning at Week 25, patients will receive weekly x 3 treatments every 12 weeks through week 51 then every 6 months and then a last treatment at Weeks 73, 74, and 75 until the tumor returns or study treatment is completed at Week 97. Cohort C Extension( Japan and the US) At Week 25, patients will receive weekly x 3 treatments every 12 weeks through week 51 then every 6 months starting at Weeks 73, 74, and 75 through Weeks 157, 158, and 159 until the tumor returns or study treatment is completed at Week 159.

Who Is Running the Clinical Trial?

CG Oncology, Inc.

Lead Sponsor

Trials

9

Recruited

900+

Findings from Research

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]

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]

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]

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]

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]

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]

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]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

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

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

Antibody-drug conjugates for urothelial carcinoma. [2023]

3. Netherlands pubmed.ncbi.nlm.nih.gov

Emerging therapies for urothelial cancer. [2012]

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

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

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

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

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

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

7. 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]

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

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

9. 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]

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

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