Academic Journal
Intravesical cretostimogene grenadenorepvec oncolytic immunotherapy in high-risk, BCG-unresponsive, non-muscle-invasive bladder cancer with carcinoma in situ (BOND-003 Cohort C): a single-arm, phase 3 trial.
| Τίτλος: | Intravesical cretostimogene grenadenorepvec oncolytic immunotherapy in high-risk, BCG-unresponsive, non-muscle-invasive bladder cancer with carcinoma in situ (BOND-003 Cohort C): a single-arm, phase 3 trial. |
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| Συγγραφείς: | Tyson MD 2nd; Department of Urology, Mayo Clinic, Phoenix, AZ, USA. Electronic address: tyson.mark@mayo.edu., Nam JK; Department of Urology, Pusan National University Yangsan Hospital, Yangsan, South Korea., Joshi SS; Department of Urology, Emory University School of Medicine, Atlanta, GA, USA., Uchio EM; Department of Urology, University of California Irvine, Irvine, CA, USA., Jung SI; Department of Urology, Chonnam National University Hwasun Hospital, Jeollanam-do, South Korea., Bivalacqua TJ; Department of Urology, University of Pennsylvania, Philadelphia, PA, USA., Steinberg GD; Department of Urology, Rush University Medical Center, Chicago, IL, USA., Shore ND; START Carolinas/Carolina Urologic Research Center, Myrtle Beach, SC, USA., Burke JM; Cody Regional Health Big Horn Basin Cancer Center, Cody, WY, USA., Kitamura H; Department of Urology, University of Toyama, Toyama, Japan., Tran B; Peter MacCallum Cancer Centre, Melbourne, VIC, Australia., Li R; Department of Genitourinary Oncology, H Lee Moffitt Cancer Center, Tampa, FL, USA. |
| Πηγή: | The Lancet. Oncology [Lancet Oncol] 2026 Aug; Vol. 27 (8), pp. 983-993. |
| Τύπος έκδοσης: | Journal Article; Clinical Trial, Phase III; Multicenter Study |
| Γλώσσα: | English |
| Στοιχεία περιοδικού: | Publisher: Lancet Pub. Group Country of Publication: England NLM ID: 100957246 Publication Model: Print Cited Medium: Internet ISSN: 1474-5488 (Electronic) Linking ISSN: 14702045 NLM ISO Abbreviation: Lancet Oncol Subsets: MEDLINE |
| Imprint Name(s): | Original Publication: London : Lancet Pub. Group, c2000- |
| Ιατρικοί όροι (MeSH): | Non-Muscle Invasive Bladder Neoplasms*/therapy , Non-Muscle Invasive Bladder Neoplasms*/pathology , Oncolytic Virotherapy*/adverse effects , Oncolytic Virotherapy*/methods , Carcinoma in Situ*/pathology , Carcinoma in Situ*/therapy , Carcinoma in Situ*/drug therapy , Carcinoma in Situ*/immunology , Urinary Bladder Neoplasms*/pathology, BCG Vaccine/administration & dosage ; BCG Vaccine/therapeutic use ; Humans ; Female ; Male ; Aged ; Administration, Intravesical ; Middle Aged ; Treatment Outcome |
| Περίληψη: | Background: There are few bladder-sparing treatment options for high-risk, BCG-unresponsive, non-muscle-invasive bladder cancer that are effective and have a manageable adverse event profile. Cretostimogene grenadenorepvec (hereafter, cretostimogene) is an oncolytic immunotherapy with dual mechanisms of action-it replicates in and lyses cancer cells with retinoblastoma-E2F pathway alterations and amplifies the immune response. We evaluated the response and safety/tolerability of cretostimogene in patients with high-risk, BCG-unresponsive, non-muscle-invasive bladder cancer. Methods: BOND-003 Cohort C is a single-arm, international, phase 3 study done in 41 centres (community practices and academic centres) located in North America, Asia, and Australia. Sites were selected through a study team-led qualification process that evaluated feasibility, protocol alignment, operational capabilities, and regulatory readiness, as applicable. We enrolled patients aged at least 18 years with Eastern Cooperative Oncology Group performance status of 0-2 and pathologically confirmed, high-risk, BCG-unresponsive, non-muscle-invasive bladder cancer with carcinoma in situ, with or without resected high-grade Ta or T1 disease. Patients received intravesical cretostimogene (1 × 1012 viral particles per 0·8 mL per week) as 6-week induction followed by maintenance; re-induction was permitted for persistent disease at 3 months. The primary endpoint was centrally confirmed complete response at any time in patients who received at least one dose of cretostimogene and completed the 3-month assessment; safety was assessed in those who received at least one dose of cretostimogene. This trial is registered with ClinicalTrials.gov (NCT04452591) and is ongoing. Findings: Between Oct 9, 2020, and Aug 3, 2023, 165 patients were assessed for eligibility; 115 patients were enrolled in the study and 112 received cretostimogene. 83 (74%) were male and 29 (26%) were female; median age was 74·0 years (IQR 68·5-79·5). As of June 23, 2025, after a median follow-up of 25·8 months (IQR 22·1-33·1), complete response at any time was observed in 83 (75% [95% CI 66·3-83·2]) of 110 patients. 71 (63%) of 112 patients had at least one treatment-related adverse event, the most common being bladder spasm in 28 (25%) patients, pollakiuria in 25 (22%) patients, and micturition urgency in 23 (21%) patients; there were no grade 3 or 4 treatment-related adverse events and no treatment-related discontinuations or deaths. Two (2%) patients had serious treatment-related adverse events (one non-infective cystitis and one urinary bladder haemorrhage, both grade 2). Interpretation: Cretostimogene showed clinically meaningful anti-tumour response, with an adverse event profile characterised predominantly by low-grade, transient events. Cretostimogene shows promise as an innovative bladder-sparing treatment for high-risk, BCG-unresponsive, non-muscle-invasive bladder cancer with carcinoma in situ. Funding: CG Oncology. (Copyright © 2026 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.) |
| Competing Interests: | Declaration of interests MDT has received institutional research support from CG Oncology, ImmunityBio, Ferring Pharmaceuticals, Pacific Edge, Protara Therapeutics, and enGene; received institutional grants for research support from the National Cancer Institute; received royalties for authoring content for UpToDate; served on advisory boards for Pacific Edge, Astellas, AstraZeneca, Ferring Pharmaceuticals, Protara Therapeutics, enGene, and UroGen; and reported other financial interests for creating digital content for Inizio, Urology Times, UroToday, Pharmacy Practice News, MJH Life Sciences, BackTable Urology, Guidepoint, and GU Oncology Now. SSJ has received institutional research support from CG Oncology. EMU has received grants from CG Oncology, Janssen, Pfizer, ImmunityBio, Merck, enGene, Protara Therapeutics, and AstraZeneca. TJB has received grant funding from National Institutes of Health Small Business Innovation Research, R01, and the US Department of Defense, served as a mentor to the American Urological Association Urology Care Foundation; participated on the scientific advisory board for UroGen and Pfizer; served as a clinical trial investigator for CG Oncology and Ferring Pharmaceuticals; and is a cofounder of OncoSTING. GDS has served as a scientific advisor or consultant within the past 12 months for CG Oncology, Photocure, Merck, Fidia Farmaceuticals, Bristol-Myers Squibb, AstraZeneca, Pfizer, enGene, Astellas, Tyra Biosciences, ImmVira, UroViu, Aura Biosciences, Vesica Health, and Protara Therapeutics; has been a member of Clinical Trial Protocol Committees for CG Oncology, Merck, Bristol-Myers Squibb, Janssen, Pfizer, Fidia Farmaceuticals, enGene Bio, and ImmVira; has declared equity stock or options with CG Oncology, enGene Bio, ImmVira, and Protara Therapeutics. NDS has received consulting fees from Accord, Alessa Therapeutics, Amgen, Asieris Pharmaceuticals, Astellas, AstraZeneca, Aura Biosciences, Bayer, BioProtect, Bristol-Myers Squibb, CG Oncology, Clarity Pharmaceuticals, Dendreon, Ferring Pharmaceuticals, FIZE Medical, Glytherix, ImmunityBio, Invitae, Janssen, Lantheus, Eli Lilly, mdxhealth, Merck, Minomic, Myriad, Novartis, Nusano, Pfizer, Photocure, PlatformQ, Promaxo, Protara Therapeutics, Sumitomo Pharma, Telix Pharmaceuticals, Tolmar, Tutelix, and UroGen; and has stock or stock options with Photocure. JMB has received consulting fees and has stock or stock options with CG Oncology. HK has received consulting fees from Kissei. BT has received grants from MSD, Amgen, Astellas, AstraZeneca, Bayer, Bristol-Myers Squibb, Ipsen, Johnson & Johnson, and Pfizer; received consulting fees from MSD, Novartis, Pfizer, Roche, Amgen, Astellas, AstraZeneca, Bayer, Bristol-Myers Squibb, Ipsen, IQVIA, Johnson & Johnson, and Merck; received honoraria from Pfizer, Amgen, Astellas, AstraZeneca, Bayer, Bristol-Myers Squibb, Ipsen, Johnson & Johnson, Merck, and MSD. RL received payment to his institution from the Department of Defense and Bladder Cancer Advocacy Network; received consulting fees from Bristol-Myers Squibb, Merck, CG Oncology, ImmunityBio, Pfizer, Johnson & Johnson, AstraZeneca, enGene, UroGen, Valar Labs, Ferring Pharmaceuticals, and Photocure; received honoraria from Johnson & Johnson; received support for attending meetings and travel from CG Oncology, Johnson & Johnson, and Predicine; participated on a data safety monitoring board or advisory board with the National Institute for Health and Care Research; and has stock or stock options with Eli Lilly, Beam Therapeutics, CRISPR Therapeutics, and Intellia Therapeutics. J-KN and SIJ declare no competing interests. |
| Molecular Sequence: | ClinicalTrials.gov NCT04452591 |
| Substance Nomenclature: | 0 (BCG Vaccine) |
| Entry Date(s): | Date Created: 20260727 Date Completed: 20260728 Latest Revision: 20261019 |
| Update Code: | 20261019 |
| DOI: | 10.1016/S1470-2045(26)00194-4 |
| PMID: | 42508433 |
| Βάση Δεδομένων: | MEDLINE |
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