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

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

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 | "Clinical Trial Registry Number: NCT06668493. The full, final text of this abstract will be available on Feb 23 at 05:00 PM EST."

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

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

New P2 trial • Bladder Cancer • Genito-urinary Cancer • Oncology • Solid Tumor • Urothelial Cancer

Evolving Pharmacotherapy for Bladder Cancer-From Non-Muscle-Invasive to Metastatic Disease-Development of Novel Therapies for BCG-Unresponsive NMIBC (PubMed, Gan To Kagaku Ryoho) - "Bladder cancer is a common malignancy in the elderly, with approximately 75% of cases diagnosed as non-muscle-invasive bladder cancer(NMIBC).Although transurethral resection of bladder tumor(TURBT)is the standard initial treatment, recurrence rates remain high, and intravesical Bacillus Calmette-Guérin(BCG)instillation has long been used as an adjuvant therapy.However, about 30% of patients develop BCG-unresponsive disease despite adequate BCG administration.Radical cystectomy is recommended in such cases, but its invasiveness and impact on quality of life(QOL)often make it impractical in real-world settings.Thus, the development of novel bladder-preserving treatments is urgently needed.In recent years, diverse approaches including immune checkpoint inhibitors(ICI), gene therapy, drug delivery systems(DDS), and oncolytic virus-based therapies have been actively investigated, with numerous clinical trials ongoing worldwide.Importantly, pembrolizumab, nadofaragene..."

Journal • 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-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

A national perspective on the management of high-risk BCG-unresponsive non-muscle-invasive bladder cancer in Romania. (PubMed, Arch Ital Urol Androl) - "Though RC remains the predominant approach for BCG-unresponsive cases, over half of urologists' report using intravesical chemotherapy, reflecting interest in bladder-sparing strategies rather than newly approved FDA agents."

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

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

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

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

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

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

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

Ferring Pharmaceuticals and Theralase(R) Technologies Announce Clinical Development Agreement to Investigate Combination Therapy in Bladder Cancer (Newsfile) - "The collaborative clinical study will evaluate ADSTILADRIN (nadofaragene firadenovec-vncg) in combination with the investigational drug Ruvidar (TLD-1433) in patients with Bacillus Calmette-Guérin-unresponsive non-muscle invasive bladder cancer carcinoma in-situ with or without papillary disease (±Ta/T1)...The new cohort of patients will explore the potential benefit of combining two innovative and complementary mechanisms of action...In the Collaborative Clinical Study, Theralase will apply to the FDA to add a new cohort to Study II. This cohort will be treated with Theralase's lead small molecule, light-activated Ruvidar, followed by treatment with Ferring's FDA-approved ADSTILADRIN."

Licensing / partnership • Trial status • Bladder Cancer

Evolving frontiers in bladder cancer immunotherapy: integrating BCG, immune checkpoints, viral vectors, nanotechnology, and CAR-based therapies. (PubMed, Front Cell Dev Biol) - "Viral vector-based approaches, including nadofaragene firadenovec and CG0070, provide localized immune activation, while cellular platforms such as CAR-T and CAR-NK therapies offer precision targeting of tumor antigens. Collectively, these strategies signify a paradigm shift from traditional intravesical therapy toward personalized and durable immunotherapeutic interventions. Identification of predictive biomarkers and rational combination strategies will be critical to improving outcomes and guiding the future management of BC."

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

Urothelial Carcinoma In Situ: Advances in Diagnosis and Management. (PubMed, Clin Genitourin Cancer) - "Recent advances in diagnostic techniques, such as narrow band imaging and photodynamic diagnosis, have improved detection accuracy, while novel therapeutic strategies, such as immune checkpoint inhibitors, thermo-chemotherapy, intravescical gene therapy (nadofaragene firadenovec), IL-15 superagonists (eg, ALT-803), and oncolytic viral therapies (eg, CG0070), are expanding the treatment landscape. Furthermore, emerging molecular and immune-related biomarkers may help predict response to therapy and guide personalized management. This review summarizes current evidence on the biology, diagnosis, and treatment of CIS, highlighting key challenges and future directions in the effort to improve patient outcomes and reduce the need for radical cystectomy."

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

A systematic review of gene-mediated therapy in BCG-unresponsive NMIBC: emerging evidence and future perspectives. (PubMed, World J Urol) - "Gene therapies represent a novel and promising therapeutic approach for BCG-unresponsive NMIBC, with significant oncological efficacy and a favorable safety profile."

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

Novel small molecule inhibitors of mitochondrial permeability transition pore (mPTP) block platelet procoagulant activity (ASH 2025) - "However, traditional therapeutic mPTP inhibitors, such as cyclosporine A, which targetcyclophilin D (CypD), exhibit off-target effects and cytotoxicity, limiting their clinical application. Injury size was comparable between groups.Altogether, our findings support MC63 and TR002 as selective inhibitors of platelet mPTP, andprocoagulant platelet activity, effectively limiting thrombosis without impairing essential hemostaticfunctions. These data highlight pharmacologic mPTP inhibition as a promising approach to saferantithrombotic therapies."

Cardiovascular • Hematological Disorders • Thrombosis • ANXA5 • PPIF • SELP

Global insights into the management of BCG-unresponsive non-muscle invasive bladder cancer: a narrative review of provider surveys. (PubMed, Transl Androl Urol) - "Preferences for intravesical chemotherapy agents differed by region: gemcitabine (Gem) was commonly used in the US and Arab countries; epirubicin and doxorubicin were favored in China; mitomycin C (MMC) was preferred in Europe. While most urologists were familiar with gemcitabine/docetaxel (Gem/Doce), its actual use in clinical practice remained limited...Notably, at the time of the surveys, newly Food and Drug Administration (FDA)-approved therapies like nadofaragene and pembrolizumab were rarely used. Global practice patterns for BCG-unresponsive disease vary widely across regions, highlighting the need for a more unified, consensus-driven approach to the use of evolving bladder-sparing therapies and clinical guidelines."

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

TR-002 for the Treatment of Advanced, Unresectable or Metastatic Solid Tumors and Unresectable or Metastatic, Refractory Pancreatic Adenocarcinoma (clinicaltrials.gov) - P1 | N=52 | Recruiting | Sponsor: University of California, Davis | Not yet recruiting ➔ Recruiting | Trial completion date: Dec 2030 ➔ Feb 2030

Enrollment open • Trial completion date • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Solid Tumor

Cost per Responder of TAR-200 vs. Other FDA-Approved Novel and Generic Treatments Among Bacillus Calmette-Guérin-Unresponsive High-Risk Non-Muscle Invasive Bladder Cancer With Carcinoma in Situ in the United States (ISPOR-EU 2025) - "Patients treated with TAR-200 monotherapy were compared to those treated with pembrolizumab, nadofaragene firadenovec (NF), nogapendekin alfa inbakicept (NAI)+BCG (with and without reinduction), or valrubicin based on published clinical trial data. TAR-200 demonstrated the highest proportion of patients achieving and sustaining CR for ≥12 months, translating to substantial cost savings per responder compared to other FDA-approved treatments for BCG-UR HR-NMIBC with CIS."

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

Gene Therapy for BCG-Unresponsive Non-Muscle Invasive Bladder Cancer: Current Evidence and Future Directions. (PubMed, Cancers (Basel)) - P1/2, P2, P3 | " Nadofaragene firadenovec, a recombinant adenovirus delivering interferon alpha-2b (IFNα2b), is the first FDA-approved gene therapy for BCG-unresponsive NMIBC with carcinoma in situ (CIS)...Cretostimogene grenadenorepvec (CG0070), an oncolytic vector, demonstrated a 47% 6-month CR rate in a phase II study (NCT02365818). Detalimogene voraplasmid (EG-70), a nonviral gene therapy, demonstrated a 47% 6-month CR in a phase I/II study (NCT04752722). Future advances are likely to focus on patient selection, novel vectors, and combination strategies to improve treatment outcomes. Gene therapy represents a significant addition to the bladder cancer treatment landscape by offering bladder-sparing alternatives where conventional therapies are limited."

Journal • Review • Bladder Cancer • Gene Therapies • Genito-urinary Cancer • Oncology • Solid Tumor • Urethral Cancer • Urothelial Cancer • IFNA1

Real-world outcomes of nadofaragene firadenovec for BCG-unresponsive non-muscle-invasive bladder cancer: A multicenter experience. (PubMed, Urol Oncol) - "Real-world data confirm the efficacy and safety of nadofaragene firadenovec, clarifying its role in the management of BCG-unresponsive NMIBC."

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

Pharmacotherapy for bladder spasm and irritative lower urinary tract symptoms associated with intravesical therapy for bladder cancer: a review of available evidence. (PubMed, Transl Androl Urol) - "This concern is of particular relevance given the recent approval of several novel intravesical agents for the treatment of Bacillus Calmette-Guérin (BCG)-unresponsive NMIBC, including nadofaragene firadenovec and nogapendekin alfa inbakicept. In this review, we evaluate the etiology of bladder spasms and irritative LUTS associated with currently approved intravesical therapies for bladder cancer and current approaches to preventing and managing them. By synthesizing available evidence and clinical practice insights, we aim to provide practical recommendations to optimize intravesical therapy for bladder cancer outcomes."

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