Evidence map›Paper›PMID 33253641›Full record

Trial reportThe Lancet. Oncology2021

Intravesical nadofaragene firadenovec gene therapy for BCG-unresponsive non-muscle-invasive bladder cancer: a single-arm, open-label, repeat-dose clinical trial.

Stephen A Boorjian, Mehrdad Alemozaffar, Badrinath R Konety, Neal D Shore, Leonard G Gomella, Ashish M Kamat, Trinity J Bivalacqua, Jeffrey S Montgomery, Seth P Lerner, Joseph E Busby and 33 more

Registry-linked trialOpen access · greenAbstract readClinical Trial, Phase IIIMulticenter Study
PubMed Full text at PMC Publisher
In one paragraph

Trial report in The Lancet. Oncology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02773849 (A Phase III, Open Label Study to Evaluate the Safety and Efficacy of INSTILADRIN®), which is not on this map. Cited by 266 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
266citing papers in PubMed, 2 pooled it
37.0field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT02773849 phase3completednot on this map

A Phase III, Open Label Study to Evaluate the Safety and Efficacy of INSTILADRIN® (rAd-IFN)/Syn3) Administered Intravesically to Patients With High-Grade, BCG Unresponsive Non-Muscle Invasive Bladder Cancer (NMIBC)

TypeinterventionalSponsorFerring PharmaceuticalsRan2016 to 2023Enrolled157ConditionsSuperficial Bladder CancerArmsADSTILADRIN
3 · Its place in the literature

Who cites it

266 citing papers in PubMed, 2 syntheses or guidelines pooled it, 417 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Trial
  4. Trial
  5. Trial
  6. Trial
  7. TAR-200 for Bacillus Calmette-Guérin-Unresponsive High-Risk Non-Muscle-Invasive Bladder Cancer: Results From the Phase IIb SunRISe-1 Study.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2025
    Trial
  8. Trial
  9. Bladder-Preserving Trimodality Treatment for High-Grade T1 Bladder Cancer: Results From Phase II Protocol NRG Oncology/RTOG 0926.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2024
    Trial
  10. Trial
  11. Trial
  12. Trial
  13. Trial
  14. A Phase II Study of Durvalumab for Bacillus Calmette-Guerin (BCG) Unresponsive Urothelial Carcinoma In Situ of the Bladder.Clinical cancer research : an official journal of the American Association for Cancer Research · 2023
    Trial
  15. Review
  16. Review
  17. Review
  18. Article
  19. Review
  20. Article

206 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

43 authors at 20 institutions in 3 countries.

Stephen A BoorjianDepartment of Urology, Mayo Clinic, Rochester, MN, USA.
Mehrdad AlemozaffarDepartment of Urology, Kaiser Permanente Los Angeles, Los Angeles, CA, USA.
Badrinath R KonetyDepartment of Urology, University of Minnesota, Minneapolis, MN, USA.
Neal D ShoreCarolina Urologic Research Center, Myrtle Beach, SC, USA.
Leonard G GomellaDepartment of Urology, Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA, USA.
Ashish M KamatDepartment of Urology, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Trinity J BivalacquaDepartment of Urology, The James Buchanan Brady Urological Institute, Johns Hopkins School of Medicine, Baltimore, MD, USA.
Jeffrey S MontgomeryDepartment of Urology, University of Michigan, Ann Arbor, MI, USA.
Seth P LernerScott Department of Urology, Dan L Duncan Cancer Center, Baylor College of Medicine, Houston, TX, USA.
Joseph E BusbyCancer Centers of the Carolinas, Greenville Hospital System, Greenville, SC, USA.
Michael PochDepartment of GU Oncology, H Lee Moffitt Cancer Center & Research Institute, Tampa, FL, USA.
Paul L CrispenDepartment of Urology, University of Florida, Gainesville, FL, USA.
Gary D SteinbergDepartment of Urology, New York University Langone Health, New York, NY, USA.
Anne K SchuckmanUSC Institute of Urology, Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA, USA.
Tracy M DownsDepartment of Urology, University of Wisconsin, Madison, WI, USA.
Robert S SvatekDepartment of Urology, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA.
Joseph MashniBanner MD Anderson Cancer Center, Gilbert, AZ, USA.
Brian R LaneDivision of Urology, Spectrum Health, Michigan State University College of Human Medicine, Grand Rapids, MI, USA.
Thomas J GuzzoDivision of Urology, University of Pennsylvania, Philadelphia, PA, USA.
Gennady BratslavskyDepartment of Urology, SUNY Upstate Medical University, Syracuse, NY, USA.
Lawrence I KarshThe Urology Center of Colorado, Denver, CO, USA.
Michael E WoodsDepartment of Urology, University of North Carolina, Chapel Hill, NC, USA.
Gordon BrownNew Jersey Urology, Bloomfield, NJ, USA.
Daniel CanterOchsner Health System, Jefferson, LA, USA.
Adam LucheyWest Virginia University Cancer Institute, Morgantown, WV, USA.
Yair LotanDepartment of Urology, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Tracey KrupskiDepartment of Urology, University of Virginia Cancer Center, Charlottesville, VA, USA.
Brant A InmanDivision of Urology, Department of Surgery, Duke University School of Medicine, Durham, NC, USA.
Michael B WilliamsUrology of Virginia, Virginia Beach, VA, USA.
Michael S CooksonDepartment of Urology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.
Kirk A KeeganDepartment of Urology, Vanderbilt University Medical Center, Nashville, TN, USA.
Gerald L AndrioleWashington University School of Medicine in St Louis, St Louis, MO, USA.
Alexander I SankinDepartment of Urology, Montefiore Medical Center, Bronx, NY, USA.
Alan BoydAlan Boyd Consultants, Crewe, UK.
Michael A O'DonnellDepartment of Urology, University of Iowa, Iowa City, IA, USA.
David SawutzFKD Therapies Oy, Kuopio, Finland.
Richard PhilipsonTrizell, Chinnor, Oxon, UK.
Ruth CollTrizell, Chinnor, Oxon, UK.
Vikram M NarayanDepartment of Urology, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
F Peter TreasurePeter Treasure Statistical Services, King's Lynn, UK.
Seppo Yla-HerttualaAI Virtanen Institute University of Eastern Finland and Science Service Center and Gene Therapy Unit, Kuopio, Finland.
Nigel R ParkerAI Virtanen Institute University of Eastern Finland and Science Service Center and Gene Therapy Unit, Kuopio, Finland.
Colin P N DinneyDepartment of Urology, University of Texas MD Anderson Cancer Center, Houston, TX, USA. Electronic address: cdinney@mdanderson.org.
The University of Texas MD Anderson Cancer Center · USParker Hannifin (United Kingdom) · GBUniversity of Eastern Finland · FIBaylor College of Medicine · USBoyds (United Kingdom) · GBCarolina Urologic Research Center · USDuke University · USJohns Hopkins Medicine · USKaiser Permanente · USMayo Clinic in Arizona · USMichigan State University · USMoffitt Cancer Center · USMontefiore Medical Center · USNew Jersey Urology · USNYU Langone Health · USOchsner Health System · USPrisma Health · USRoyal Statistical Society · GBSidney Kimmel Cancer Center · USSUNY Upstate Medical University · US

Funding

Tumor Evolution and Metastasis ProgramP30CA016672 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI Scott Kopetz · 1985 to 2026
$290.8M
West Virginia IDEA-CTRU54GM104942 · NIGMS · WEST VIRGINIA UNIVERSITY · PI Sally Lynn Hodder · 2012 to 2026
$81.0M
Viral VectorP30CA086862 · NCI · UNIVERSITY OF IOWA · PI Douglas Robert Spitz · 2000 to 2026
$70.0M
NCI NIH HHS P30 CA016672NIGMS NIH HHS U54 GM104942
6 · The paper itself

Abstract

backgroundBCG is the most effective therapy for high-risk non-muscle-invasive bladder cancer. Nadofaragene firadenovec (also known as rAd-IFNa/Syn3) is a replication-deficient recombinant adenovirus that delivers human interferon alfa-2b cDNA into the bladder epithelium, and a novel intravesical therapy for BCG-unresponsive non-muscle-invasive bladder cancer. We aimed to evaluate its efficacy in patients with BCG-unresponsive non-muscle-invasive bladder cancer.

methodsIn this phase 3, multicentre, open-label, repeat-dose study done in 33 centres (hospitals and clinics) in the USA, we recruited patients aged 18 years or older, with BCG-unresponsive non-muscle-invasive bladder cancer and an Eastern Cooperative Oncology Group status of 2 or less. Patients were excluded if they had upper urinary tract disease, urothelial carcinoma within the prostatic urethra, lymphovascular invasion, micropapillary disease, or hydronephrosis. Eligible patients received a single intravesical 75 mL dose of nadofaragene firadenovec (3 × 10

findingsBetween Sept 19, 2016, and May 24, 2019, 198 patients were assessed for eligibility. 41 patients were excluded, and 157 were enrolled and received at least one dose of the study drug. Six patients did not meet the definition of BCG-unresponsive non-muscle-invasive bladder cancer and were therefore excluded from efficacy analyses; the remaining 151 patients were included in the per-protocol efficacy analyses. 55 (53·4%) of 103 patients with carcinoma in situ (with or without a high-grade Ta or T1 tumour) had a complete response within 3 months of the first dose and this response was maintained in 25 (45·5%) of 55 patients at 12 months. Micturition urgency was the most common grade 3-4 study drug-related adverse event (two [1%] of 157 patients, both grade 3), and there were no treatment-related deaths.

interpretationIntravesical nadofaragene firadenovec was efficacious, with a favourable benefit:risk ratio, in patients with BCG-unresponsive non-muscle-invasive bladder cancer. This represents a novel treatment option in a therapeutically challenging disease state.

fundingFKD Therapies Oy.

Indexed as

Drug Resistance, NeoplasmGenetic TherapyGenetic VectorsAdenoviridaeAdministration, IntravesicalAgedBCG VaccineCarcinoma in SituDisease ProgressionFemaleHumansInterferon alpha-2MaleMiddle AgedNeoplasm GradingNeoplasm InvasivenessBCG VaccineInterferon alpha-2

Identifiers

PMID33253641
PMCPMC7988888
OpenAlexW3108799736

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.