CG0070 for Bladder Cancer
(BOND-003 Trial)
Recruiting in Palo Alto (17 mi)
+88 other locations
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 3
Recruiting
Sponsor: CG Oncology, Inc.
Must not be taking: Systemic anti-cancer therapy
Disqualifiers: Muscle invasive cancer, Metastatic cancer, Uncontrolled hypertension, others
No Placebo Group
Pivotal Trial (Near Approval)
Prior Safety Data
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.12345
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.678910
Research Team
CO
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.
See 2 more
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.
See 4 more
Trial 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 (Virus Therapy)
Trial OverviewThe 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
2Treatment groups
Experimental Treatment
Group I: Cohort P(Japan and United States Only) :Open to EnrollmentExperimental Treatment2 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 ClosedExperimental Treatment2 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.
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Wake Forest UniversityWinston-Salem, NC
Skyline Urology - Sherman OaksSherman Oaks, CA
Prisma HealthGreenville, SC
Colorado Clinical ResearchLakewood, CO
More Trial Locations
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Who Is Running the Clinical Trial?
CG Oncology, Inc.
Lead Sponsor
Trials
9
Patients Recruited
900+
References
Evaluation of Therapeutic Targets in Histological Subtypes of Bladder Cancer. [2021]Histologically, bladder cancer is a heterogeneous group comprising urothelial carcinoma (UC), squamous cell carcinoma, adenocarcinomas (ACs), urachal carcinomas (UrCs), and small cell neuroendocrine carcinomas (SCCs). However, all bladder cancers have been treated so far uniformly, and targeted therapy options are still limited. Thus, we aimed to determine the protein expression/molecular status of commonly used cancer targets (programmed cell death 1 ligand 1 (PD-L1), mismatch repair (MMR), androgen and estrogen receptors (AR/ER), Nectin-4, tumor-associated calcium signal transducer 2 (Tacstd2, Trop-2), epidermal growth factor receptor (EGFR), human epidermal growth factor receptor 2 (HER2), and fibroblast growth factor receptor 3 (FGFR3)) to give first insights into whether patients with SCC, AC/UrCs, and squamous-differentiated carcinomas (Sq-BLCA) of the bladder could be eligible for targeted therapies. In addition, for MMR-deficient tumors, microsatellite instability was analyzed. We completed our own data with molecular data from The Cancer Genome Atlas (TCGA). We present ratios for each drug and cumulative ratios for multiple therapeutic options for each nonurothelial subtype. For example, 58.9% of SCC patients, 33.5% of AC/UrCs patients, and 79.3% of Sq-BLCA patients would be eligible for at least one of the analyzed targets. In conclusion, our findings hold promise for targeted therapeutic approaches in selected patients in the future, as various drugs could be applied according to the biomarker status.
Antibody-drug conjugates for urothelial carcinoma. [2023]The standard of care for advanced urothelial carcinoma includes platinum chemotherapy and immunotherapy. Antibody-drug conjugates (ADCs), originally developed for hematologic malignancies, involve potent cytotoxic agents linked to antibodies that recognize tumor-specific antigens; this rational drug design allows for more on-target efficacy, while mitigating systemic toxicity. Herein, we review the emerging landscape of ADCs in urothelial carcinoma. The anti-Nectin-4 ADC enfortumab vedotin has demonstrated efficacy in prospective studies in patients with advanced urothelial carcinoma in several settings either alone or in combination with pembrolizumab. The anti-Trop-2 ADC sacituzumab govitecan has also shown efficacy in single-armed studies. Both conjugates have full or accelerated approval from the Food and Drug Administration. Common adverse events include rash and neuropathy for enfortumab vedotin and myelosuppression and diarrhea for sacituzumab govitecan. Several anti-human epidermal growth factor receptor 2 ADCs are in clinical trials, and in localized bladder cancer, the anti-epithelial cell adhesion molecule ADC oportuzumab monatox is being studied in patients refractory to intravesical bacillus calmette-guerin therapy. Antibody-drug conjugates for urothelial carcinoma are approved and emerging as therapies for patients with advanced urothelial carcinoma, filling a prior void for treatment of progressive disease. Ongoing studies are also evaluating these agents in the neoadjuvant and adjuvant settings.
Emerging therapies for urothelial cancer. [2012]Urothelial carcinoma is one of the leading causes of death in Europe and the United States. Despite its chemosensitivity, median overall survival for advanced disease is still nearly 1 year. Most second-line chemotherapeutic agents tested have been disappointing. Thus, new treatment strategies are clearly needed. This review focuses on emerging therapies in urothelial carcinoma. Results from recent clinical trials, investigating the activity of new generation cytostatic agents, as well as results from studies assessing the toxicity and efficacy of novel targeted therapies, are discussed. In this setting, anti-epidermal growth factor receptor, angiogenesis, and phosphatidylinositol 3-kinase/mammalian target of rapamycin inhibitors account for the majority of phase I and II trials.
Conceptual Framework for Therapeutic Development Beyond Anti-PD-1/PD-L1 in Urothelial Cancer. [2019]Platinum-based chemotherapy has been the standard of care in advanced urothelial cancer, but long-term outcomes have remained poor. Immune checkpoint inhibitors, with their favorable toxicity profiles and noteworthy efficacy, have steered a new era in advanced urothelial cancer, with five agents targeting the PD-1/PD-L1 pathway approved by the U.S. Food and Drug Administration (FDA). However, most patients do not achieve response, whereas immunotherapy-related adverse events may cause morbidity, increased health care use, and-rarely-mortality. Therefore, there is an urgent need for additional therapeutic modalities across the disease spectrum. A plethora of clinical trials are ongoing in various disease settings, including chemotherapy regimens, radiotherapy, antibody-drug conjugates, agents targeting additional immune checkpoint pathways, vaccine, cytokines, adoptive cell therapies, as well as targeted and anti-angiogenic agents. Two agents, enfortumab vedotin and erdafitinib, have breakthrough designation by the FDA but are not approved yet (at the time of this paper's preparation). Novel combinations with various treatment modalities and optimal sequencing of active therapies are being investigated in prospective clinical trials. Evaluation of new treatments has met with substantial challenges for many reasons, for example, molecular heterogeneity, clonal evolution, and genomic instability. In the era of precision molecular medicine, and because patients do not respond uniformly to current therapies, there is a growing need for identification and validation of biomarkers that can accurately predict treatment response and assist in patient selection. Here, we review current updates and future directions of experimental therapeutics in urothelial cancer, including examples (but not an exhaustive list) of ongoing clinical trials.
MEK is a promising target in the basal subtype of bladder cancer. [2020]While many resources exist for the drug screening of bladder cancer cell lines in 2D culture, it is widely recognized that screening in 3D culture is more representative of in vivo response. Importantly, signaling changes between 2D and 3D culture can result in changes to drug response. To address the need for 3D drug screening of bladder cancer cell lines, we screened 17 bladder cancer cell lines using a library of 652 investigational small-molecules and 3 clinically relevant drug combinations in 3D cell culture. Our goal was to identify compounds and classes of compounds with efficacy in bladder cancer. Utilizing established genomic and transcriptomic data for these bladder cancer cell lines, we correlated the genomic molecular parameters with drug response, to identify potentially novel groups of tumors that are vulnerable to specific drugs or classes of drugs. Importantly, we demonstrate that MEK inhibitors are a promising targeted therapy for the basal subtype of bladder cancer, and our data indicate that drug screening of 3D cultures provides an important resource for hypothesis generation.
AdCD40L immunogene therapy for bladder carcinoma--the first phase I/IIa trial. [2021]Immunotherapy with Bacillus Calmette-Guerin (BCG) instillation is recommended for high-risk, non-muscle invasive bladder cancer. Bacillus Calmette-Guerin is not effective in advanced tumors, and better alternatives are warranted. Immunostimulating gene therapy with adenoviral vectors expressing CD40 ligand (AdCD40L) has shown efficacy in tumor models. CD40 ligand stimulates systemic immunity and may be effective in local and invasive human disease.
Bacillus Calmette-Guérin versus gemcitabine for intravesical therapy in high-risk superficial bladder cancer: a randomised prospective study. [2022]To evaluate the safety, tolerability and efficacy of adjuvant intravesical gemcitabine versus bacillus Calmette-Guérin (BCG) in the treatment of high-risk superficial bladder cancer.
Intravesical Infusion of Oncolytic Virus CG0070 in the Treatment of Bladder Cancer. [2023]CG0070 is a conditionally replicating oncolytic adenovirus that preferentially replicates within and kills Rb-defective cancer cells. It has been used successfully in an intravesical formulation to treat Bacillus Calmette-Guerin (BCG) unresponsive carcinoma in situ (CIS) containing non-muscle-invasive bladder cancer. As a self-replicating biologic, it shares many characteristics with intravesical BCG but has other unique features. Herein, we detail recommended standardized protocols for bladder infusion of CG0070 for the treatment of bladder cancer and provide many useful tips for trouble shooting.
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]CG0070 is a replication-competent oncolytic adenovirus that targets bladder tumor cells through their defective retinoblastoma pathway. Prior reports of intravesical CG0070 have shown promising activity in patients with high-grade non-muscle invasive bladder cancer (NMIBC) who previously did not respond to bacillus Calmette-Guérin (BCG). However, limited accrual has hindered analysis of efficacy, particularly for pathologic subsets. We evaluated interim results of a phase II trial for intravesical CG0070 in patients with BCG-unresponsive NMIBC who refused cystectomy.
Replacement Instead of Discontinuation of Bacillus Calmette-Guérin Instillation in Non-Muscle-Invasive Bladder Cancer. [2023]To evaluate the efficacy of intravesical chemotherapy replacement in patients with intermediate- and high-risk non-muscle-invasive bladder cancer (NMIBC), who underwent bacillus Calmette-Guérin (BCG) instillation but discontinued due to global shortages or toxicity of BCG.