^
    24d
    Advancements in the Diagnosis, Treatment, and Risk Stratification of Non-Muscle Invasive Bladder Cancer. (PubMed, Curr Oncol Rep)
    Advances in immunotherapy, including the use of pembrolizumab and nadofaragene firadenovec, offer options for BCG-unresponsive NMIBC, though challenges like cost and adverse effects remain. Future directions highlight the need for biomarker-driven models to refine treatment paradigms, reduce overtreatment, and improve long-term outcomes. Continued clinical trials are essential to validate these approaches and address unmet needs in NMIBC care.
    Review • Journal • PD(L)-1 Biomarker • IO biomarker
    |
    FGFR3 (Fibroblast growth factor receptor 3) • TERT (Telomerase Reverse Transcriptase)
    |
    Keytruda (pembrolizumab) • Adstiladrin (nadofaragene firadenovec-vncg)
    1m
    A Study to Compare Quality of Life and Compliance in Patients Receiving High-dose Interferon Versus Pegylated Interferon in Patients With Surgically Resected Melanoma (clinicaltrials.gov)
    P=N/A, N=50, Completed, St. Luke's Hospital and Health Network, Pennsylvania | Unknown status --> Completed
    Trial completion • HEOR • Compliance
    |
    ViraferonPeg (peginterferon-α-2b)
    1m
    LUNAR: Low-grade UTUC Treated With Nadofaragene Firadenovec Administered to Renal Pelvis (clinicaltrials.gov)
    P1/2, N=20, Not yet recruiting, Ferring Pharmaceuticals | Initiation date: Nov 2024 --> Mar 2025
    Trial initiation date
    |
    Adstiladrin (nadofaragene firadenovec-vncg)
    2ms
    TEM-GBM: A Study Evaluating Temferon in Patients with Glioblastoma & Unmethylated MGMT (clinicaltrials.gov)
    P1/2, N=27, Recruiting, Genenta Science | Trial completion date: Dec 2024 --> Dec 2025 | Trial primary completion date: Dec 2023 --> Dec 2025
    Trial completion date • Trial primary completion date
    |
    MGMT (6-O-methylguanine-DNA methyltransferase)
    |
    Temferon (Autologous CD34+ enriched HSPCs expressing interferon-alpha 2)
    3ms
    A Study of Modakafusp Alfa (TAK-573) Given by Itself and Together With Pembrolizumab in Adults With Advanced or Metastatic Solid Tumors (clinicaltrials.gov)
    P1/2, N=45, Terminated, Takeda | Completed --> Terminated; Study was terminated early due to futility.
    Trial termination
    |
    BRAF (B-raf proto-oncogene) • CTLA4 (Cytotoxic T-Lymphocyte Associated Protein 4)
    |
    BRAF V600E • BRAF V600
    |
    Keytruda (pembrolizumab) • modakafusp alfa (TAK-573)
    3ms
    iinnovate-2: A Study of Modakafusp Alfa in Adult Participants With Multiple Myeloma (clinicaltrials.gov)
    P1, N=15, Completed, Takeda | Trial primary completion date: Jan 2024 --> Jun 2024
    Trial primary completion date
    |
    lenalidomide • bortezomib • Darzalex (daratumumab) • carfilzomib • pomalidomide • modakafusp alfa (TAK-573)
    3ms
    iinnovate-1: A Study of Modakafusp Alfa on Adult Participants With Relapsed/Refractory Multiple Myeloma (clinicaltrials.gov)
    P1/2, N=272, Completed, Takeda | Trial primary completion date: Feb 2024 --> Jul 2024
    Trial primary completion date
    |
    modakafusp alfa (TAK-573)
    3ms
    TEM-GU: A Clinical Gene Therapy Study with Hematopoietic Stem Cells for the Treatment, with Single Dose of Temferon, of Patients Suffering from Metastatic Renal Cell Carcinoma (clinicaltrials.gov)
    P1/2, N=12, Recruiting, Genenta Science
    New P1/2 trial • Gene therapy • Metastases
    |
    Keytruda (pembrolizumab) • Cabometyx (cabozantinib tablet) • Temferon (Autologous CD34+ enriched HSPCs expressing interferon-alpha 2)
    3ms
    iinnovate-1: A Study of Modakafusp Alfa on Adult Participants With Relapsed/Refractory Multiple Myeloma (clinicaltrials.gov)
    P1/2, N=272, Completed, Takeda | Active, not recruiting --> Completed
    Trial completion
    |
    modakafusp alfa (TAK-573)
    3ms
    Peginterferon α-2b Injection for Hydroxyurea Resistant or Intolerant ET (clinicaltrials.gov)
    P2, N=27, Recruiting, Xiamen Amoytop Biotech Co., Ltd. | Not yet recruiting --> Recruiting
    Enrollment open
    |
    hydroxyurea
    4ms
    A Follow-up Study of Peginterferon Alfa-2b Combined With TDF in Patients With Chronic Hepatitis B (clinicaltrials.gov)
    P=N/A, N=350, Enrolling by invitation, Xiamen Amoytop Biotech Co., Ltd.
    New trial
    4ms
    ABLE-42: A Trial to Evaluate Efficacy of Reinduction With Nadofaragene Firadenovec in Subjects With CIS ± High-grade Ta/T1 and no Complete Response to First Nadofaragene Firadenovec Dose. (clinicaltrials.gov)
    P4, N=0, Withdrawn, Ferring Pharmaceuticals | N=25 --> 0 | Recruiting --> Withdrawn
    Enrollment change • Trial withdrawal
    |
    Adstiladrin (nadofaragene firadenovec-vncg)
    4ms
    Single-cell RNA sequencing analysis identifies acute changes in the tumor microenvironment induced by interferon α gene therapy in a murine bladder cancer model. (PubMed, Front Immunol)
    This single-cell analysis builds upon our understanding of the impact of Ad-IFNα on tumor cells and other compartments of the microenvironment. These data will help identify mechanisms to improve patient selection and therapeutic efficacy of Nadofaragene firadenovec.
    Preclinical • Journal • PD(L)-1 Biomarker • IO biomarker • Gene therapy
    |
    IFNA1 (Interferon Alpha 1)
    |
    PD-L1 expression • PD-1 expression
    |
    Adstiladrin (nadofaragene firadenovec-vncg)
    4ms
    Safety and Efficacy of FE 999326 Administered Intravesically to Japanese Subjects With High-grade, BCG Unresponsive, Non-muscle Invasive Bladder Cancer (NMIBC) (clinicaltrials.gov)
    P3, N=25, Active, not recruiting, Ferring Pharmaceuticals | Recruiting --> Active, not recruiting
    Enrollment closed
    |
    Adstiladrin (nadofaragene firadenovec-vncg)
    4ms
    ABLE-41: ADSTILADRIN Early Utilization and Outcomes in the Real World Setting (clinicaltrials.gov)
    P=N/A, N=400, Recruiting, Ferring Pharmaceuticals | N=800 --> 400
    Enrollment change
    |
    Adstiladrin (nadofaragene firadenovec-vncg)
    4ms
    INFINITE: Efficacy & Safety of RAd-IFN Administered with Celecoxib & Gemcitabine in Patients with Malignant Pleural Mesothelioma (clinicaltrials.gov)
    P3, N=53, Active, not recruiting, Ferring Ventures Limited | Trial completion date: Nov 2024 --> Apr 2026 | Trial primary completion date: Nov 2023 --> Mar 2024
    Trial completion date • Trial primary completion date • Combination therapy
    |
    MSLN (Mesothelin) • EFEMP1 (EGF Containing Fibulin Extracellular Matrix Protein 1)
    |
    gemcitabine • Adstiladrin (nadofaragene firadenovec-vncg) • celecoxib oral
    5ms
    LUNAR: Low-grade UTUC Treated with Nadofaragene Firadenovec Administered to Renal Pelvis (clinicaltrials.gov)
    P1/2, N=20, Not yet recruiting, Ferring Pharmaceuticals
    New P1/2 trial
    |
    Adstiladrin (nadofaragene firadenovec-vncg)
    5ms
    ABLE-22: A Trial to Evaluate Intravesical Nadofaragene Firadenovec Alone or in Combination With Chemotherapy or Immunotherapy in Participants With High-grade BCG Unresponsive Non-muscle Invasive Bladder Cancer (clinicaltrials.gov)
    P2, N=150, Recruiting, Ferring Pharmaceuticals | Not yet recruiting --> Recruiting
    Enrollment open • Combination therapy
    |
    Keytruda (pembrolizumab) • gemcitabine • docetaxel • Adstiladrin (nadofaragene firadenovec-vncg)
    5ms
    ABLE-32: Trial of Nadofaragene Firadenovec vs. Observation in Participants With Intermediate Risk Non-Muscle Invasive Bladder Cancer (clinicaltrials.gov)
    P3, N=454, Recruiting, Ferring Pharmaceuticals | Not yet recruiting --> Recruiting
    Enrollment open
    |
    Adstiladrin (nadofaragene firadenovec-vncg)
    5ms
    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
    |
    HER-2 (Human epidermal growth factor receptor 2) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • ARID1A (AT-rich interaction domain 1A) • ELF3 (E74 Like ETS Transcription Factor 3)
    |
    HER-2 mutation
    |
    UroAmp
    |
    Adstiladrin (nadofaragene firadenovec-vncg)
    5ms
    The importance of IFNα2A (Roferon-A) in HSV-1 latency and T cell exhaustion in ocularly infected mice. (PubMed, PLoS Pathog)
    The absence of IFNα2A significantly reduced the levels of latency and T cell exhaustion but not time of reactivation compared with control mice. Our results suggest that blocking IFNα2A expression may be a useful tool in reducing latency and the subsequent side effects associated with higher levels of latency.
    Preclinical • Journal
    |
    IFNG (Interferon, gamma) • IFNA1 (Interferon Alpha 1) • IFNB1 (Interferon Beta 1)
    |
    IFNG expression
    |
    Roferon A (recombinant interferon alfa-2a)
    6ms
    Clinical use of nadofaragene firadenovec-vncg. (PubMed, Ther Adv Urol)
    Implementation of these recommendations will ensure efficient real-world use of nadofaragene firadenovec and the development of useful training materials and relevant standard operating procedures to help support a clinic's treatment for patients with BCG-unresponsive NMIBC with CIS. Video Abstract https://vimeo.com/user17898099/review/953723559/e18af7ec43.
    Review • Journal
    |
    IFNA1 (Interferon Alpha 1)
    |
    Adstiladrin (nadofaragene firadenovec-vncg)
    6ms
    iinnovate-3: A Study of Modakafusp Alfa Together With Daratumumab Adults With Relapsed or Refractory Multiple Myeloma (clinicaltrials.gov)
    P1/2, N=15, Completed, Takeda | Active, not recruiting --> Completed | N=58 --> 15 | Trial completion date: Mar 2025 --> May 2024 | Trial primary completion date: Mar 2025 --> May 2024
    Trial completion • Enrollment change • Trial completion date • Trial primary completion date • Combination therapy
    |
    Darzalex Faspro (daratumumab and hyaluronidase-fihj) • modakafusp alfa (TAK-573)
    6ms
    A Phase 2 Multicenter, Randomized, Open-label Study to Evaluate the Pharmacokinetic, Safety and Efficacy of Peginterferon Alfa-2b Injection in Subjects With Essential Thrombocythemia Who Are Resistant to or Intolerant of Hydroxyurea (ChiCTR2400088120)
    P2, N=27, Not yet recruiting, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College; Institute of Hematology
    New P2 trial
    |
    hydroxyurea
    7ms
    Peginterferon α-2b Injection for Hydroxyurea Resistant or Intolerant ET (clinicaltrials.gov)
    P2, N=27, Not yet recruiting, Xiamen Amoytop Biotech Co., Ltd.
    New P2 trial
    |
    hydroxyurea
    7ms
    The Evolution of Nadofaragene Firadenovec: A Review and the Path Forward. (PubMed, Bladder Cancer)
    Nadofaragene leverages the cytotoxic, anti-angiogenic, and immune-modulatory roles of interferon to effectively treat NMIBC that is resistant to BCG. Ongoing studies of resistance mechanisms and prognostic biomarkers have been promising; these will ultimately improve patient selection and allow for the modulation of factors in the tumor or immune microenvironment to further increase therapeutic response.
    Review • Journal
    |
    IFNA1 (Interferon Alpha 1) • IFNA2 (Interferon Alpha 2)
    |
    Adstiladrin (nadofaragene firadenovec-vncg)
    7ms
    KEYNOTE-F95: First In Human Study of CX-801 in Advanced Solid Tumors (clinicaltrials.gov)
    P1, N=121, Recruiting, CytomX Therapeutics | Not yet recruiting --> Recruiting
    Enrollment open • Combination therapy • Metastases
    |
    Keytruda (pembrolizumab)
    7ms
    STAR: First in Human Study With NG-641, a Tumour Selective Transgene Expressing Adenoviral Vector (clinicaltrials.gov)
    P1, N=186, Active, not recruiting, Akamis Bio | Recruiting --> Active, not recruiting | Trial completion date: Dec 2023 --> Dec 2024 | Trial primary completion date: Dec 2023 --> Aug 2024
    Enrollment closed • Trial completion date • Trial primary completion date • Metastases • Viral vector
    |
    NG-641
    7ms
    MOAT: A Study of NG-641 and Pembrolizumab in Squamous Cell Carcinoma of the Head and Neck (clinicaltrials.gov)
    P1, N=36, Active, not recruiting, Akamis Bio | Recruiting --> Active, not recruiting
    Enrollment closed • Combination therapy
    |
    Keytruda (pembrolizumab) • NG-641
    7ms
    NEBULA: Study of NG-641 in Combination With Nivolumab in Metastatic or Advanced Epithelial Tumours (clinicaltrials.gov)
    P1, N=30, Active, not recruiting, Akamis Bio | Recruiting --> Active, not recruiting | Phase classification: P1a/1b --> P1 | Trial completion date: Jul 2024 --> Dec 2024 | Trial primary completion date: May 2024 --> Aug 2024
    Enrollment closed • Phase classification • Trial completion date • Trial primary completion date • Combination therapy • Metastases • Viral vector
    |
    Opdivo (nivolumab) • NG-641
    7ms
    ABLE-22: A Trial to Evaluate Intravesical Nadofaragene Firadenovec Alone or in Combination With Chemotherapy or Immunotherapy in Participants With High-grade BCG Unresponsive Non-muscle Invasive Bladder Cancer (clinicaltrials.gov)
    P2, N=150, Not yet recruiting, Ferring Pharmaceuticals
    New P2 trial • Combination therapy
    |
    Keytruda (pembrolizumab) • gemcitabine • docetaxel • Adstiladrin (nadofaragene firadenovec-vncg)
    8ms
    ABLE-42: A Trial to Evaluate Efficacy of Reinduction With Nadofaragene Firadenovec in Subjects With CIS ± High-grade Ta/T1 and no Complete Response to First Nadofaragene Firadenovec Dose. (clinicaltrials.gov)
    P4, N=25, Recruiting, Ferring Pharmaceuticals | Not yet recruiting --> Recruiting
    Enrollment open
    |
    Adstiladrin (nadofaragene firadenovec-vncg)
    8ms
    ABLE-32: Trial of Nadofaragene Firadenovec vs. Observation in Participants With Intermediate Risk Non-Muscle Invasive Bladder Cancer (clinicaltrials.gov)
    P3, N=454, Not yet recruiting, Ferring Pharmaceuticals
    New P3 trial
    |
    Adstiladrin (nadofaragene firadenovec-vncg)
    8ms
    iinnovate-2: A Study of Modakafusp Alfa in Adult Participants With Multiple Myeloma (clinicaltrials.gov)
    P1, N=15, Completed, Takeda | Active, not recruiting --> Completed | N=120 --> 15
    Trial completion • Enrollment change • Combination therapy
    |
    lenalidomide • bortezomib • Darzalex (daratumumab) • carfilzomib • pomalidomide • modakafusp alfa (TAK-573)
    9ms
    Intravesical instillation-based mTOR-STAT3 dual targeting for bladder cancer treatment. (PubMed, J Exp Clin Cancer Res)
    The bi-specific siRNA strategy, encapsulated in an adenovirus, could be a promising tool to augment cancer treatment efficacy and overcome conventional therapy limitations associated with "undruggability." Hence, we propose that dual targeting of mTOR and STAT3 is an advantageous strategy for intravesical therapy using adenoviruses.
    Journal
    |
    CD8 (cluster of differentiation 8) • STAT3 (Signal Transducer And Activator Of Transcription 3)
    |
    Adstiladrin (nadofaragene firadenovec-vncg) • cretostimogene grenadenorepvec (CG0070)
    9ms
    First In Human Study of CX-801 in Advanced Solid Tumors (clinicaltrials.gov)
    P1, N=121, Not yet recruiting, CytomX Therapeutics
    New P1 trial • Combination therapy • Metastases
    |
    Keytruda (pembrolizumab)
    9ms
    Safety and Efficacy of FE 999326 Administered Intravesically to Japanese Subjects With High-grade, BCG Unresponsive, Non-muscle Invasive Bladder Cancer (NMIBC) (clinicaltrials.gov)
    P3, N=24, Recruiting, Ferring Pharmaceuticals | Trial completion date: Dec 2028 --> Dec 2029 | Trial primary completion date: Dec 2024 --> Oct 2025
    Trial completion date • Trial primary completion date
    |
    Adstiladrin (nadofaragene firadenovec-vncg)
    10ms
    iinnovate-2: A Study of Modakafusp Alfa in Adult Participants With Multiple Myeloma (clinicaltrials.gov)
    P1, N=120, Active, not recruiting, Takeda | Trial completion date: Jan 2028 --> Jun 2024 | Trial primary completion date: Jul 2025 --> Jan 2024
    Trial completion date • Trial primary completion date • Combination therapy
    |
    lenalidomide • bortezomib • Darzalex (daratumumab) • carfilzomib • pomalidomide • modakafusp alfa (TAK-573)
    11ms
    ABLE-42: A Phase 4, Multi-center, Open Label Trial to Evaluate Efficacy of Retreatment With Nadofaragene Firadenovec in Subjects With CIS ± High-grade Ta/T1 and no Complete Response to First Nadofaragene Firadenovec Dose (clinicaltrials.gov)
    P4, N=25, Not yet recruiting, Ferring Pharmaceuticals
    New P4 trial
    |
    Adstiladrin (nadofaragene firadenovec-vncg)
    1year
    Urinary minimal residual disease detection predicts recurrence in BCG-unresponsive NIMBC and quantifies molecular response to nadofaragene firadenovec (AUA 2024)
    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
    |
    HER-2 (Human epidermal growth factor receptor 2) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • MSI (Microsatellite instability) • ARID1A (AT-rich interaction domain 1A) • ELF3 (E74 Like ETS Transcription Factor 3) • SOX4 (SRY-Box Transcription Factor 4)
    |
    HER-2 mutation
    |
    UroAmp
    |
    Adstiladrin (nadofaragene firadenovec-vncg)
    1year
    A First-in-Human Dose Escalation and Expansion Study to Evaluate Intratumoral Administration of SAR441000 as Monotherapy and in Combination With Cemiplimab in Patients With Advanced Solid Tumors (clinicaltrials.gov)
    P1, N=77, Terminated, Sanofi | Completed --> Terminated; Sponsor terminated the study for non-safety reasons
    Trial termination • Combination therapy • Metastases
    |
    Libtayo (cemiplimab-rwlc) • SAR441000
    1year
    A Study of Peginterferon Alfa-2b Combined With TDF in Patients With Chronic Hepatitis B (clinicaltrials.gov)
    P3, N=475, Completed, Xiamen Amoytop Biotech Co., Ltd. | Active, not recruiting --> Completed
    Trial completion