Cretostimogene Grenadenorepvec for Bladder Cancer
Palo Alto (17 mi)Overseen byRobert Svatek, MD
Age: 18+
Sex: Any
Travel: May be covered
Time Reimbursement: Varies
Trial Phase: Phase 3
Recruiting
Sponsor: CG Oncology, Inc.
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, randomized trial designed to evaluate the RFS of TURBT followed by cretostimogene grenadenorepvec versus TURBT followed by observation for the treatment of participants with IR-NMIBC.
Is Cretostimogene Grenadenorepvec a promising treatment for bladder cancer?The information provided does not mention Cretostimogene Grenadenorepvec, so we cannot determine if it is a promising treatment for bladder cancer based on the given articles.56789
What data supports the idea that Cretostimogene Grenadenorepvec for Bladder Cancer (also known as: Cretostimogene Grenadenorepvec, CG0070) is an effective treatment?The available research does not provide specific data on the effectiveness of Cretostimogene Grenadenorepvec for Bladder Cancer. Instead, it discusses other treatments like enfortumab vedotin and sacituzumab govitecan, which have shown effectiveness in treating advanced urothelial carcinoma, a type of bladder cancer. These treatments have demonstrated response rates of 40% to 52% in patients who did not respond to other therapies. However, there is no direct comparison or data available for Cretostimogene Grenadenorepvec in the provided information.12378
What safety data exists for Cretostimogene Grenadenorepvec (CG0070) for bladder cancer?The provided research does not contain specific safety data for Cretostimogene Grenadenorepvec (CG0070) for bladder cancer. The articles focus on other treatments, particularly Enfortumab Vedotin, and do not mention CG0070 or its safety profile.24789
Do I have to stop taking my current medications for this trial?The trial protocol does not specify whether you need to stop taking your current medications.
Eligibility Criteria
This trial is for people with a type of bladder cancer called Intermediate Risk Non-Muscle Invasive Bladder Cancer (IR-NMIBC). Participants should have had certain low-grade tumors treated within the last 12 months or high-grade tumors smaller than 3 cm, and all visible disease must be removed recently. They need to have good organ function.Inclusion Criteria
My bladder cancer has come back within a year or is larger/multiple low-grade tumors.
Treatment Details
The study compares two approaches after tumor removal surgery (TURBT): one group receives an experimental therapy called Cretostimogene Grenadenorepvec, while the other group is just observed without additional treatment. The goal is to see which method is better at preventing cancer recurrence.
2Treatment groups
Experimental Treatment
Active Control
Group I: Cretostimogene after TURBTExperimental Treatment2 Interventions
Following screening confirmation of IR-NMIBC and complete resection of the tumor, participants will be treated with adjuvant cretostimogene.
Group II: Observation after TURBTActive Control1 Intervention
Following screening confirmation of IR-NMIBC and complete resection of tumor, participants will enter observation.
Participants who recur with IR-NMIBC after TURBT and observation will be offered treatment with cretostimogene as per the treatment schedule in Arm A. This arm will be called the Extension Arm.
Find a clinic near you
Research locations nearbySelect from list below to view details:
Arkansas Urology PALittle Rock, AR
Sun Kim UrologyOrange, CA
Urology Associates, PCLone Tree, CO
Wichita Urology GroupWichita, KS
More Trial Locations
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Who is running the clinical trial?
CG Oncology, Inc.Lead Sponsor
References
Novel approaches with targeted therapies in bladder cancer. Therapy of bladder cancer by blockade of the epidermal growth factor receptor family. [2019]The improved understanding of the molecular biology of urothelial malignancies is helping to define the role of new targets and prognostic indices that can direct the most appropriate choice of treatment for advanced disease. Many human tumors express high levels of growth factors and their receptors that can be used as potential therapeutical targets. Tyrosine-kinase receptors, including many growth factor receptors such the receptors for epidermal growth factor (EGF), vascular endothelial growth factor (VEGF), and Her2/neu, have been found overexpressed in urothelial tumors. For many of these growth factor receptors, the degree of expression has been associated with the progression of cancer and a poor prognosis. Among the best studied growth factor receptors are the two members of EGF receptor familiy EGFr (ErbB-1), and Her2/neu (ErbB-2). Several preclinical studies in bladder cancer models, have confirmed that systemic administration of growth factor inhibitors inhibits the growth and metastasis of human transitional cell carcinoma established in the bladder wall of athymic nude mice. Additional studies indicate that therapy with EGFR inhibitors enhances the activity of conventional cytoreductive chemotherapeutic agents, in part by inhibiting tumor cell proliferation, angiogenesis, and inducing apoptosis. Novel targeted therapy hold promise to improve the current results of bladder cancer treatment. Based on the success seen with anti-HER2 monoclonal antibodies (Herceptin) and the promising results with EGFR targeted agents (IMC-C225 Cetuximab, ZD1389 Iressa, OSI-774 Tarceva, GW 57016) in other tumor types, and based on the results obtained in preclinical models, there is a great interest in assessing these agents in patients with bladder cancer. Several trials are now ongoing testing these new agents alone or in combination with chemotherapy in bladder cancer patients. The integration of these newer biologic agents, probably to supplement rather than to supplant chemotherapeutic drugs, should be a primary direction of research with the objective to interfere with multiple aspects of bladder cancer progression. However, the value of integration of biologically targeted agents into combined modality treatment for patients with bladder cancer has still to be proven.
Intravesical Therapy for the Treatment of Nonmuscle Invasive Bladder Cancer: A Systematic Review and Meta-Analysis. [2022]We systematically review the benefits and harms of intravesical therapies for nonmuscle invasive bladder cancer.
Clinical Overview of Enfortumab Vedotin in the Management of Locally Advanced or Metastatic Urothelial Carcinoma. [2020]The treatment landscape for locally advanced or metastatic urothelial carcinoma has broadened significantly over recent years. New therapeutic options include immunotherapy with checkpoint inhibitors and targeted therapy with erdafitinib. Despite these advances, gaps remain in the selection and sequencing of optimal therapies. Treatment decisions are often influenced by several patient-specific factors such as tolerability and biomarker expression. Following progression while receiving front- and second-line therapies, there is no widely accepted standard of care for patients. Enrollment into a clinical trial is recommended in all lines of therapy for advanced disease. Antibody-drug conjugates have recently emerged as novel therapeutics allowing for targeted delivery of chemotherapeutic agents. Enfortumab vedotin, a nectin-4-targeted antibody conjugated with monomethyl auristatin E, is the first-in-class therapeutic option and has demonstrated unprecedented response rates following progression on chemotherapy and immunotherapy for advanced disease with a tolerable safety profile. As a result, a biologics license application was submitted to the US FDA in July 2019. Ongoing clinical trials are aiming to further establish the role of enfortumab vedotin in urothelial carcinoma. In this article, we highlight the safety and efficacy of enfortumab vedotin for patients with advanced bladder cancer, ongoing clinical trials, clinical pharmacology, and pharmacokinetics.
Enfortumab Vedotin in urothelial cancer. [2021]The treatment landscape for metastatic urothelial cancer (mUC) beyond first-line platinum-based chemotherapy has changed significantly over the last 5 years with the recent approvals of the immune checkpoint inhibitors (ICIs), fibroblast growth factor receptor (FGFR) inhibitors and most recently Enfortumab Vedotin (EV). EV is a novel antibody-drug conjugate (ADC), that delivers monomethyl auristatin E (MMAE), a microtubule-disrupting agent, inside cells harboring the cell surface nectin-4 receptor. In mUC, EV has shown encouraging response rates and received accelerated approval from the Food and Drug Administration (FDA) in December 2019 in the post-platinum and ICI setting. EV is generally well tolerated, with the main toxicities being neuropathy, skin rash, alopecia and fatigue. Notably EV can also be administered to patients with renal dysfunction, which is commonly a concern in this patient population. EV is now being tested in combination strategies and in earlier disease settings in urothelial cancers. In this review, we will discuss its mechanism of action, clinical trials leading to FDA approval as well as ongoing trials and future directions.
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]Intravesical BCG is active against non-muscle invasive bladder cancer (NMIBC), but bladder cancer will recur and even progress in a significant number of patients. To improve the response rate, N-803, an IL-15 superagonist was administered in combination with BCG. To evaluate the safety and efficacy associated with the use of intravesical N-803 and BCG in patients with BCG-naïve NMIBC. This phase 1b clinical trial used a 3 + 3 dose-escalation design. Participants were enrolled from July 2014 and July 2015, with follow-up and analyses through January 15, 2021. Eligibility criteria included histologically confirmed non-muscle invasive urothelial carcinoma of intermediate or high risk who had not received prior treatment with intravesical BCG (ie, BCG-naïve). All 9 participants met the eligibility criteria, received treatment according to the protocol, and were included in all analyses. Treatment was done once weekly for 6 consecutive weeks with bladder infusion of the standard dose of BCG, 50 mg/instillation, in combination with increasing doses of N-803 (100, 200, or 400 µg N-803 per instillation). No DLTs were noted in any of the dose cohorts. All adverse events (AEs) were manageable and less than grade 3. During the 2-year follow-up, all 9 participants were disease free. Furthermore, 6 y after treatment, all 9 participants (100%) were disease free with no evidence of disease progression and an intact bladder. This phase 1b trial found the combination of intravesical N-803 and BCG to be associated with modest toxic effects, low immunogenicity, and substantial prolonged antitumoral activity; phase 2 trials are in progress.
Novel intravesical therapeutics in the treatment of non-muscle invasive bladder cancer: Horizon scanning. [2022]Non-muscle-invasive bladder cancer (NMIBC) is a common and heterogeneous disease; many patients develop recurrent or progress to muscle-invasive disease. Intravesical drug therapy is a pillar in the current management of NMIBC; notwithstanding, Mitomycin C (MMC) and Bacillus Calmette-Guérin (BCG) have numerous limitations including international supply issues, and local and systemic toxicity. Here we review novel intravesical therapeutic options and drug delivery devices with potential for clinical use in the treatment of NMIBC.
Targeted Treatment of Locally Advanced and Metastatic Urothelial Cancer: Enfortumab Vedotin in Context. [2022]Enfortumab vedotin (EV) is a novel antibody-drug conjugate that is the first in class to be FDA-approved for use in patients with treatment-refractory urothelial cancer. Enfortumab is comprised of an antibody targeting nectin-4, widely expressed in urothelial cancers, with an monomethyl auristatin E (MMAE) chemotherapy payload. To date, trials in urothelial cancers refractory to platinum-based chemotherapy, and or checkpoint inhibitors, have shown the drug is very active, with overall responses ranging from 40% to 52%. This includes patients with visceral metastasis, a known predictor of poor prognosis. EV is fairly well tolerated, including in patients who are not candidates for cisplatin, a common urothelial cancer population with significant unmet need. Side effects such as skin toxicity, fatigue, and blood sugar elevations are generally manageable with supportive care and dose modifications. Peripheral neuropathy is common and can be dose-limiting in responding patients, and rare serious skin toxicities have been reported. Trials in various disease states and in combination with checkpoint inhibitors and other agents are ongoing, with additional indications likely in the future for EV in urothelial cancer.
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.
Current and Emerging Treatments for Urothelial Carcinoma: A Focus on Enfortumab Vedotin. [2023]Urothelial carcinoma is a common malignancy that affects the urinary system, with bladder cancer being the most prevalent form. Although the management of early-stage disease has seen significant improvements, the treatment of locally advanced and metastatic urothelial carcinoma remains challenging. Over the past decade, there has been an explosion in the number of therapies available for the treatment of advanced disease, with immune checkpoint inhibitors and antibody-drug conjugates leading the way. Enfortumab vedotin is an antibody-drug conjugate that targets Nectin-4, a protein that is overexpressed in urothelial carcinoma cells. In clinical trials, it has shown promising outcomes for the treatment of advanced urothelial carcinoma that has progressed after chemotherapy or immunotherapy. The US Food and Drug Administration has granted expedited approval for enfortumab vedotin in the treatment of advanced urothelial carcinoma. This review provides an overview of the current and emerging treatments for urothelial carcinoma, with a particular focus on enfortumab vedotin. We discuss the mechanisms of action, clinical efficacy, safety, and ongoing research of enfortumab vedotin, along with the current landscape of other approved therapies and promising agents in development. The aim of this review is to provide a comprehensive and up-to-date summary of the available treatment options for urothelial carcinoma, including their limitations and future prospects.