Adstiladrin (nadofaragene firadenovec-vncg) / Ferring, FKD Therapies, Royalty - LARVOL DELTA

An Indirect Treatment Comparison of Nogapendekin Alfa Inbakicept pmln Plus Bacillus Calmette-Guérin and Nadofaragene Firadenovec vncg in BCG unresponsive Non Muscle Invasive Bladder Cancer with Carcinoma In Situ with or without Papillary Tumors (MA-AUA 2026) - No abstract available

Bladder Cancer • Genito-urinary Cancer • Oncology • Solid Tumor

ABLE-22: Safety and efficacy evaluation of nadofaragene firadenovec alone or in combination with chemotherapy or immunotherapy—A randomized, open-label, phase 2 study. (ASCO-GU 2025) - P2 | "Bladder-preserving treatment options for patients with BCG-unresponsive NMIBC with CIS ± Ta/T1 include intravesical gene therapy (nadofaragene firadenovec-vncg), intravesical chemotherapy (gemcitabine and docetaxel), and immunotherapy (intravenous pembrolizumab and intravesical nogapendekin alfa inbakicept-pmln). Exploratory endpoints include changes in expression of potential biomarkers in blood and urine. Results from this investigational, randomized, multicenter, open-label study evaluating the safety and efficacy of nadofaragene firadenovec alone or in combination with chemotherapy or immunotherapy are expected July 2028."

Clinical • Combination therapy • IO biomarker • P2 data • Bladder Cancer • Genito-urinary Cancer • Oncology • Solid Tumor

Intravesical nadofaragene firadenovec gene therapy for BCG-unresponsive non-muscle-invasive bladder cancer: a single-arm, open-label, repeat-dose clinical trial. (PubMed, Lancet Oncol) - P3 | "Intravesical 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."

Clinical • Journal • Bladder Cancer • Gene Therapies • Genito-urinary Cancer • Nephrology • Oncology • Solid Tumor • Urothelial Cancer

UPDATED EFFICACY AND SAFETY OF ORAL ERDAFITINIB IN PATIENTS WITH BACILLUS CALMETTE-GUÉRIN–UNRESPONSIVE, HIGH-RISK NON-MUSCLE–INVASIVE BLADDER CANCER WITH FGFR3/2 ALTERATIONS IN THOR-2 COHORT 2 (SUO 2023) - P2 | "Treatment options for patients with bacillus Calmette-Guérin (BCG)-unresponsive CIS who refuse/are ineligible for radical cystectomy include pembrolizumab, intravesical chemotherapy, or nadofaragene firadenovec. Data from this trial provide first evidence of occurrence of FGFR alterations in CIS and demonstrate the promising and durable efficacy of an FGFR inhibitor such as erdafitinib in patients with BCG-unresponsive CIS with FGFR alterations. Safety data were consistent with the known safety profile of erdafitinib."

Clinical • Acute Kidney Injury • Bladder Cancer • Chronic Kidney Disease • Dental Disorders • Genito-urinary Cancer • Hypotension • Infectious Disease • Metabolic Disorders • Nephrology • Oncology • Renal Disease • Retinal Disorders • Septic Shock • Solid Tumor • Stomatitis • Urothelial Cancer • Xerostomia • FGFR3

Neoadjuvant Intravesical Nadofaragene Firadenovec With Gemcitabine, Cisplatin and Durvalumab for the Treatment of Muscle Invasive Bladder Cancer, TRIFECTA Trial (clinicaltrials.gov) - P2 | N=33 | Not yet recruiting | Sponsor: University of Washington | Initiation date: Sep 2026 ➔ Dec 2026

Trial initiation date • Bladder Cancer • Genito-urinary Cancer • Oncology • Solid Tumor • Urothelial Cancer

Re-induction with nadofaragene firadenovec: a fragile signal that should not influence clinical practice. (PubMed, Transl Androl Urol) - No abstract available

Journal

EFFICACY OF INTRAVESICAL NADOFARAGENE FIRADENOVEC FOR PATIENTS WITH BCG-UNRESPONSIVE CARCINOMA IN SITU OF THE BLADDER: 36-MONTH FOLLOW-UP FROM A PHASE 3 TRIAL (SUO 2023) - P3 | "Intravesical nadofaragene firadenovec, administered once every three months, demonstrated a sustained durability of response in patients with BCG-unresponsive CIS±Ta/T1 papillary disease. Nadofaragene firadenovec represents a novel treatment option for BCG-unresponsive NMIBC with a favorable benefit-to-risk ratio. *All patients had passed 36 months at data cutoff on 09 September 2021."

Clinical • P3 data • Bladder Cancer • Gene Therapies • Genito-urinary Cancer • Oncology • Solid Tumor

Efficacy of Intravesical Nadofaragene Firadenovec for Patients with BCG-Unresponsive Non-muscle Invasive Bladder Cancer: 5 Year Follow-Up from a Phase 3 Trial. (PubMed, J Urol) - P3 | "Only 5 patients (4 with CIS and 1 with Ta/T1) experienced clinical progression to muscle-invasive disease. At 60 months, Nadofaragene firadenovec-vncg allowed bladder preservation in nearly half of the patients and proved to be a safe option for BCG-unresponsive NMIBC."

Journal • P3 data • Bladder Cancer • Gene Therapies • Genito-urinary Cancer • Oncology • Solid Tumor

Minimal Residual Disease Detection with Urine-derived DNA Is Prognostic for Recurrence-free Survival in Bacillus Calmette-Guérin-unresponsive Non-muscle-invasive Bladder Cancer Treated with Nadofaragene Firadenovec. (PubMed, Eur Urol Oncol) - P2 | "Urinary MRD testing after nadofaragene firadenovec induction provided statistically significant prognostication of recurrence among phase 2 trial participants."

Journal • Minimal residual disease • Residual disease • Bladder Cancer • Gene Therapies • Genito-urinary Cancer • Oncology • Solid Tumor • Urothelial Cancer • ARID1A • ELF3 • HER-2 • PIK3CA • TP53

Urinary minimal residual disease detection predicts recurrence in BCG-unresponsive NIMBC and quantifies molecular response to nadofaragene firadenovec. (ASCO-GU 2024) - P2 | "uMRD enables quantitative assessment of molecular response to drug treatment. uMRD-determined pre-treatment disease burden assessment can support stratification of control and intervention arms in future treatment trials."

Minimal residual disease • Residual disease • Bladder Cancer • Genito-urinary Cancer • Urothelial Cancer • ARID1A • ELF3 • HER-2 • MSI • PIK3CA • SOX4 • TP53

LUNAR: Safety and efficacy evaluation of nadofaragene firadenovec instilled into the renal pelvis in subjects with low-grade upper tract urothelial carcinoma—A single-arm, open-label phase 1/2 trial. (ASCO-GU 2026) - P1/2 | "Secondary efficacy endpoints include duration of response and urinary excretion of IFN-α2b protein. Results from this trial are expected in 2029."

Clinical • P1/2 data • Bladder Cancer • Genito-urinary Cancer • Oncology • Solid Tumor • Urothelial Cancer • IFNA1

ABLE-41: Nadofaragene firadenovec-vncg early use and outcomes in a real-world setting in the United States. (ASCO-GU 2024) - P | "The estimated follow-up period is 24 months, until study discontinuation, or withdrawal. Final results from this large, prospective, multi-institutional, real-world registry providing early use and outcomes of nadofaragene firadenovec are expected December 2026."

Clinical • Real-world • Real-world evidence • Bladder Cancer • Genito-urinary Cancer

Advances in intravesical therapy for non-muscle-invasive bladder cancer (PubMed, Zhong Nan Da Xue Xue Bao Yi Xue Ban) - "With regard to targeted therapy, erdafitinib has achieved breakthrough progress in patients with BCa harboring fibroblast growth factor receptor (FGFR) mutations or fusions. Novel drug delivery systems, such as the mitomycin-containing hydrogel formulation UGN-102, has been approved for marketing by the U.S. Food and Drug Administration (FDA). In addition, gene therapies such as nadofaragene firadenovec have entered clinical practice, while novel treatment modalities, including viral therapies, have progressed to the clinical trial stage. An in-depth understanding of the latest advances in intravesical therapy for NMIBC may provide evidence-based support for clinical decision-making and inform future combination and individualized treatment strategies."

IO biomarker • Journal • Review • Bladder Cancer • Gene Therapies • Genito-urinary Cancer • Oncology • Solid Tumor • FGFR

ABLE-32: A randomized, controlled, phase 3b clinical trial of nadofaragene firadenovec-vncg versus observation in patients with intermediate-risk non–muscle-invasive bladder cancer. (ASCO-GU 2025) - P3 | "Exploratory endpoints include effect on potential biomarkers and health-related quality of life. Final results are expected in 2031."

Clinical • P3 data • Bladder Cancer • Genito-urinary Cancer • Oncology • Solid Tumor

THE GAIN TRIAL: Gemcitabine Alternating with INtravesical BCG randomized against BCG alone for patients with recurrent "BCG-exposed" high grade NMIBC (ALLIANCE A032303/ NCT07000084) (AUA 2026) - P1/2, P3 | "gemcitabine plus docetaxel) or TAR-200.Any prior treatment with any systemic or intravesical agents for NMIBC is allowed, regardless of whether it is given either alone or in prior combination with BCG (ie. Prior treatment with pembrolizumab, sasanlimab, durvalumab, other immune checkpoint inhibitors, nadofaragene firadenovec, nogapendekin alfa inbakicept, cretostimogene grenadenorepvec, etc.) are all allowed...Notable exclusion criteria include current/prior MIBC and prior intolerance to BCG or any other intravesical therapy. Other notable aspects of the trial include: (1) the reduced burden on investigators & research teams due to the NCI's new streamlined data initiative, (2) pragmatic inclusion/exclusion criteria and pragmatic design to improve generalizability of results, and (3) cystoscopic biopsies/TURBT at week 13/month 3 for all participants (both CIS & "papillary only") for multiple reasons including to allow for earlier..."

Clinical • IO biomarker • Bladder Cancer • Prostate Cancer • Urothelial Cancer

ABLE-32: A randomized, controlled, phase 3b clinical trial of nadofaragene firadenovec-vncg versus observation in patients with intermediate-risk non–muscle-invasive bladder cancer. (ASCO 2025) - P3 | "Exploratory endpoints include effect on potential biomarkers and health-related quality of life. Final results are expected in 2031."

Clinical • P3 data • Bladder Cancer • Gene Therapies • Genito-urinary Cancer • Oncology • Solid Tumor

ABLE-22: Safety and efficacy evaluation of nadofaragene firadenovec alone or in combination with chemotherapy or immunotherapy—A randomized, open-label, phase 2 study. (ASCO 2025) - P3 | "Bladder-preserving treatment options for patients with BCG-unresponsive NMIBC with CIS ± Ta/T1 include intravesical gene therapy (nadofaragene firadenovec-vncg), intravesical chemotherapy (gemcitabine and docetaxel), and immunotherapy (intravenous pembrolizumab and intravesical nogapendekin alfa inbakicept-pmln). Exploratory endpoints include changes in expression of potential biomarkers in blood and urine. Results from this investigational, randomized, multicenter, open-label study evaluating the safety and efficacy of nadofaragene firadenovec alone or in combination with chemotherapy or immunotherapy are expected July 2028."

Clinical • Combination therapy • IO biomarker • P2 data • Bladder Cancer • Gene Therapies • Genito-urinary Cancer • Oncology • Solid Tumor

ABLE-41, a real-world evidence study for bladder cancer patients treated with nadofaragene firadenovec: Baseline patient characteristics and demographics. (ASCO 2025) - P | "Early data from the real-world usage of nadofaragene firadenovec in this study demonstrates patients are older than those in the phase 3 trial but despite having 1 subject with ECOG status > 2, they self-report low levels of pain and limitations on daily living activities. Inclusion of patients outside the FDA label and clinical guidelines may provide unique insights and hypothesis generation."

Clinical • HEOR • Real-world • Real-world evidence • Bladder Cancer • CNS Disorders • Depression • Gene Therapies • Genito-urinary Cancer • Mood Disorders • Oncology • Pain • Psychiatry • Solid Tumor

Updated Analysis of Cost-Effectiveness Among Bladder-Sparing Treatments for BCG-Unresponsive CIS: Incorporating Recently Approved and Established Therapies (AUA 2026) - "Source of Funding: n/a INTRODUCTION AND OBJECTIVES: The FDA has approved multiple therapies for BCG-unresponsive CIS including pembrolizumab, nadofaragene, nogapendekin/BCG, and in Sept 2025, the gemcitabine intravesical system. Gemcitabine/docetaxel (Gem/Doce) remains a commonly used off-label generic treatment option... Based on available data and current Medicare pricing, Gem/Doce is the most cost-effective first-line BST for BCG-unresponsive CIS; among FDA-approved agents, pembrolizumab is the least expensive strategy. Incorporation of newer gemcitabine-based delivery systems modestly extends quality-adjusted survival but at substantially higher modeled cost. These findings underscore the need for value-aligned pricing and thoughtful sequencing to optimize both patient outcomes and healthcare sustainability."

Cost effectiveness • HEOR

Deep learning-based automated identification of papillary bladder cancer from endoscopic still images using SE-ResNeXt-50. (PubMed, World J Urol) - "Recent clinical advancements with novel agents-such as gemcitabine-releasing intravesical systems (TAR-200), nadofaragene firadenovec, and the IL-15 superagonist complex (N-803)-fundamentally require a clinically "tumor-free" state through complete resection to ensure maximum therapeutic efficacy. Although background artifacts like air bubbles or mesh-like structures occasionally influence the signal, the system maintains high diagnostic reliability. Our findings suggest that this deep learning framework provides robust decision support, facilitating the rigorous complete resection necessary for successful intervention with next-generation intravesical agents."

Journal • Bladder Cancer • Genito-urinary Cancer • Oncology • Solid Tumor

Mitochondrial permeability transition critically regulates of highly procoagulant platelet phenotypes (ISTH 2026) - "Therapeutic targeting of this pathway has been constrained by physiologic requirements for platelet PS exposure and off-target effects of cyclophilin-dependent agents such as cyclosporines. Aims To define the role of mPTP opening in procoagulant platelet generation using cyclophilin D-independent small molecule mPTP inhibitors, including the isoxazole MC63 and triazoles TR001 and TR002...Cyclophilin-independent mPTP inhibition selectively suppresses thrombogenic platelet activity while sparing core hemostatic functions, supporting mPTP targeting as a hemostasis- sparing antithrombotic strategy. DOI*10.1016/j.rpth.2026.105176"

Cardiovascular • Hematological Disorders • Thrombosis • ANXA5 • PPIF

Emerging Intravesical Therapies for Non-Muscle-Invasive Bladder Cancer. (PubMed, Urol Clin North Am) - "Recent advances include UGN-102 for low-grade/intermediate-risk disease and multiple FDA-approved agents-nadofaragene firadenovec, TAR-200, and nogapendekin alfa inbakicept-for BCG-unresponsive disease. Ongoing trials of TAR-210, cretostimogene, and other combination regimens promise to further expand options. Comparative studies and real-world evidence will be critical to define optimal sequencing, benchmark outcomes against radical cystectomy, and address quality-of-life considerations."

Journal • Review • Bladder Cancer • Genito-urinary Cancer • Oncology • Solid Tumor

Analysis of real-world re-induction outcomes with nadofaragene firadenovec in patients with Bacillus Calmette-Guérin (BCG)-unresponsive non-muscle-invasive bladder cancer. (PubMed, Transl Androl Urol) - "Patients had received a mean of 11 prior BCG doses; other prior therapy included gemcitabine (n=4) and pembrolizumab (n=5). Nine patients experienced treatment failure after first re-induction with nadofaragene firadenovec; two received a second re-induction dose without response. In this real-world cohort, approximately 30% of patients achieved a CR after re-induction with nadofaragene firadenovec, supporting the proof of concept of this approach."

Journal • Real-world evidence • Bladder Cancer • Gene Therapies • Genito-urinary Cancer • Oncology • Solid Tumor • Urology

Immunotherapy in bladder cancer: a systematic review of clinical trials and therapeutic advances. (PubMed, BMC Urol) - "Intravesical immunotherapies, particularly Nogapendekin Alfa Inbakicept and Bacillus Calmette-Guerin and Nadofaragene, demonstrate superior efficacy, significant response durability, and favorable safety profiles in treating bladder cancer compared to systemic checkpoint inhibitors, which display moderate efficacy and notable safety concerns. These findings strongly support prioritizing intravesical therapies in non-muscle-invasive bladder cancer management, especially for patients who are unresponsive to Bacillus Calmette-Guerin. Future research should focus on head-to-head randomized controlled trials and biomarker-driven patient selection to optimize clinical outcomes."

IO biomarker • Journal • Bladder Cancer • Gene Therapies • Genito-urinary Cancer • Oncology • Solid Tumor

Non-replicating adenoviral vectors for cancer gene therapy. (PubMed, Adv Cancer Res) - "To date, three cancer gene therapy products, Gendicine, Adstiladrin, and Papzimeos, that are based on non-replicating adenovirus have been approved for commercialization. As we will explore here, non-replicating adenoviral vectors continue to be developed for cancer gene therapy."

Journal • Gene Therapies • Oncology