Anktiva (nogapendekin alfa inbakicept-pmln) / ImmunityBio - LARVOL DELTA

QUILT-3.076: Study of Autologous M-CENK in Subjects With Locally Advanced or Metastatic Solid Tumors (clinicaltrials.gov) - P1 | N=50 | Active, not recruiting | Sponsor: ImmunityBio, Inc. | Trial completion date: May 2025 ➔ May 2026 | Trial primary completion date: May 2025 ➔ May 2026

Trial completion date • Trial primary completion date • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Pancreatic Cancer • Solid Tumor • CD4

ImmunityBio Receives Conditional Marketing Authorization Recommendation from the European Medicines Agency for ANKTIVA with BCG for Non-Muscle Invasive Bladder Cancer Carcinoma in Situ—A First in Europe (Businesswire) - "The decision was based on a review of the results of a single-arm clinical trial in 100 adults with BCG-unresponsive NMIBC who received ANKTIVA in combination with BCG."

CHMP • Bladder Cancer

N-803 in Patients With Progressive Synovial Sarcoma and Myxoid/Round Cell Liposarcoma Previously Treated With Adoptive Cellular Therapy (clinicaltrials.gov) - P1 | N=8 | Not yet recruiting | Sponsor: Northwestern University

New P1 trial • Liposarcoma • Oncology • Sarcoma • Solid Tumor • Synovial Sarcoma

First-in-human immunotherapy targeting lymphopenia in recurrent Glioblastoma Multiform (GBM): NAI and PD-L1 t-haNK plus Bevacizumab with complete response (SNO 2025) - "Anktiva (nogapendekin alfa-inbakicept, NAI), an IL-15 receptor superagonist, is the first treatment to address lymphopenia by proliferating NK and T-cells. Administered in combination with PD-L1 targeted high-affinity CAR-NK cells (PD-L1 t-haNK) and bevacizumab, treating lymphopenia was hypothesized to elicit tumor response in recurrent GBMMETHODS : Phase I QUILT-3.078 trial of participants with GBM (IDH WT) who recurred after surgery and temozolomide/XRT...This is the first report of disease response in participants with refractory GBM who received orchestrated temporal immunotherapy with CAR-NK cells combined with an IL-15 receptor superagonist and bevacizumab to treat lymphopenia. Updated data to be presented."

Clinical • First-in-human • Lymphopenia • P1 data • Brain Cancer • Cardiovascular • Glioblastoma • Hematological Malignancies • Pulmonary Embolism • Respiratory Diseases • Solid Tumor • IL15 • PD-L1

Phase I/II Study of the Combination Immunotherapy Regimen: SX-682, TriAdeno Vaccine, Retifanlimab and IL-15 Agonist N-803 (STAR15) for Metastatic Colorectal Cancer (mCRC) (clinicaltrials.gov) - P1/2 | N=60 | Recruiting | Sponsor: National Cancer Institute (NCI) | Trial completion date: Oct 2028 ➔ Oct 2030 | Trial primary completion date: Oct 2025 ➔ Oct 2027

Trial completion date • Trial primary completion date • Colorectal Cancer • Oncology • 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

CARMEN-803: N-803 Maintenance Therapy Post CAR T-cell Therapy in Patients With Relapsed or Refractory B-cell Non-Hodgkin Lymphomas (clinicaltrials.gov) - P1 | N=13 | Not yet recruiting | Sponsor: University of Utah | Initiation date: Sep 2025 ➔ Dec 2025

Trial initiation date • B Cell Non-Hodgkin Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

Pre-treatment Microbiome Diversity and Function is associated with Expansion of Cytotoxic and Regulatory Immune Populations after N-803 treatment in People with HIV. (PubMed, bioRxiv) - "MaAsLin2 analyses further associated short-chain fatty acid (SCFA)-producing taxa and pathways with increased immune activation markers. These results indicate that gut microbiome diversity prior to immunotherapy influences host response and suggest that microbiome-based strategies could improve efforts to cure HIV."

IO biomarker • Journal • Human Immunodeficiency Virus • Infectious Disease • CD8

First-in-human immunotherapy targeting lymphopenia in recurrent Glioblastoma Multiform (GBM): NAI and PD-L1 t-haNK plus Bevacizumab with complete response (WFNOS 2025) - "Anktiva (nogapendekin alfa-inbakicept, NAI), an IL-15 receptor superagonist, is the first treatment to address lymphopenia by proliferating NK and T-cells. Administered in combination with PD-L1 targeted high-affinity CAR-NK cells (PD-L1 t-haNK) and bevacizumab, treating lymphopenia was hypothesized to elicit tumor response in recurrent GBMMETHODS : Phase I QUILT-3.078 trial of participants with GBM (IDH WT) who recurred after surgery and temozolomide/XRT...This is the first report of disease response in participants with refractory GBM who received orchestrated temporal immunotherapy with CAR-NK cells combined with an IL-15 receptor superagonist and bevacizumab to treat lymphopenia. Updated data to be presented."

Clinical • First-in-human • Lymphopenia • P1 data • Brain Cancer • Cardiovascular • Glioblastoma • Hematological Malignancies • Pulmonary Embolism • Respiratory Diseases • Solid Tumor • IL15 • PD-L1

CTLA-4 Blockade Results in the Enrichment of Proliferative CD56 dimCD16 + NK Cells Following Infusion of Haploidentical Donor Memory-like Natural Killer Cells Plus IL-15 Superagonist in a Phase 1 Trial (ASH 2023) - P1 | "In the current study, we hypothesized the use of ipilimumab (IPI) will abrogate Treg-mediated inhibition and thus allow enhanced proliferation, activation, and anti-tumor responses of the adoptively transferred CIML NK cells...All patients received lymphodepletion with fludarabine (25 mg/m 2 x 5 days) and cyclophosphamide (60 mg/kg x 2 days) during days -6 to -2 prior to haploidentical CIML NK cell infusion on day 0 (5-10 x 10 6 cells/kg=dose level 0) followed by N-803 (15 mcg/kg subcutaneously) starting on day +1 every 21-days for 4-doses...Tumor regression was associated with CD56 dimCD16 + NK cell expansion. Further work is required to elucidate the mechanism by which IPI exposure is associated with the expansion of specific subsets of CIML NK cells."

IO biomarker • P1 data • Graft versus Host Disease • Head and Neck Cancer • Immunology • Oncology • Solid Tumor • CD8 • IFNG • IL12A • IL18 • LAMP1 • NCAM1

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

ANKTIVA Access Update (Businesswire) - "ANKTIVA selected as preferred drug of choice for NMIBC patients with CIS, with or without papillary tumors by a large medication contracting organization with ~80 million lives under management. The Company remains committed to patients through the expansion of the recombinant BCG (rBCG) early access program (EAP) and its copay assistance program with as low as $25 copay payments for qualifying patients."

Commercial • Bladder Cancer

ANKTIVA Unit Growth: 467% unit sales volume growth in year-to-date 2025 compared to fiscal year 2024. (Businesswire)

Sales • Bladder Cancer

The Company shared updated QUILT-3.032 trial data showing durable 36-month progression-free survival and bladder-sparing benefits of ANKTIVA plus Bacillus Calmette-Guérin (BCG). (Businesswire)

P2/3 data • Bladder Cancer

ImmunityBio has initiated enrollment in ResQ201A, a global, randomized Phase 3 study evaluating ANKTIVA in combination with TEVIMBRA (BeOne) and docetaxel versus docetaxel alone in patients with checkpoint inhibitor-resistant NSCLC. (Businesswire)

Trial status • Non Small Cell Lung Cancer

ATR inhibitor tuvusertib induces immunogenic modulation and sensitizes prostate carcinoma to natural killer cell-mediated cytotoxicity which is further enhanced by the IL-15 superagonist N-803 (SITC 2025) - "Impedance-based real-time cell analysis was used to assess the lysis of tuvusertib-treated PCa cells upon co-incubation with PBMC-derived NK cells in the presence or absence of anti-PD-L1 avelumab, PD-L1 targeting high-affinity NK cell line (PD-L1 t-hANK) cells, or TRAIL ligand. TRAIL signaling blockade mitigated the NK cell lysis of tuvusertib-treated cells. In vivo, tuvusertib and N-803 combination therapy resulted in the significant tumor growth control of the DU145 xenograft (p<0.0001) and the prolonged survival of the animals (p<0.05).Conclusions This study supports the combination of the ATR inhibitor tuvusertib with the anti-PD-L1 avelumab and/or IL-15 superagonist N-803 for prostate carcinoma.Acknowledgements This work was funded by the Intramural Research Program of the Center for Cancer Research, National Cancer Institute (NCI), National Institutes of Health and via Cooperative Research and Development Agreements (CRADAs) between the NCI and the..."

IO biomarker • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • BCL2L1 • CDKN1A • TNFRSF10B

Interrogation of the peripheral immunome from QuEST1 in men with castration-resistant prostate cancer (SITC 2025) - P1/2 | "The combination phase I/II Quick Efficacy Seeking Trial (QuEST1, NCT03493945) was designed to generate a tumor-directed immune response with BNVax (a vaccine targeting the transcription factor brachyury, involved in invasion and metastasis) and facilitate the resulting anti-tumor activity with ICB (with bintrafusp alfa (BA), a bifunctional agent providing dual inhibition of PD-L1 and TGF-β) and a lymphocyte stimulating immunocytokine (the IL-15 receptor superagonist NAI (N-803), Anktiva®). These data support the continued investigation of easily accessible peripheral biomarkers, including ALC, in patients with CRPC and suggest that evaluation of multiple circulating biomarkers may be beneficial in predicting clinical response.Ethics Approval All subjects gave written informed consent. Study protocol (NCT03493945) was approved by the NIH's IRB, and conducted in accordance with institutional and federal guidelines."

IO biomarker • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • CD4 • CD8 • IFNG • IL15 • TGFB1

The advantages of NK cell vaccines in solid carcinoma clinical trials: conducted by various biology strategy and technology. (PubMed, Front Med (Lausanne)) - "The study illustrated: Dendritic cell-based vaccine platforms (e.g., ilixadencel), cytokine-based vaccine platforms (e.g., ALT-803), NK receptor agonist antibodies (e.g., AFM24) and mRNA/LNP-based vaccine platforms (e.g., BNT116) It has shown early efficacy in solid tumors such as non-small cell lung cancer, triple-negative breast cancer, and glioblastoma (with partial ORR of 30-50% and DCR of 80-100%), and the safety is comparatively manageable (the incidence of grade ≥3 adverse events is less compared to T-cell therapy). In the future, combinatorial regimens (e.g., sequential application of PD-1 inhibitors) need to be optimized, an iPSC-NK universal platform developed, and perioperative application scenarios explored. NK vaccines, by reshaping the immune microenvironment, will be an attractive strategy to break the bottlenecks in the treatment of solid tumors."

Journal • Review • Brain Cancer • Breast Cancer • Glioblastoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer

QUILT2023: Nogapendekin Alfa Inbakicept for Advanced Non-Small Cell Lung Cancer (clinicaltrials.gov) - P3 | N=1538 | Active, not recruiting | Sponsor: ImmunityBio, Inc. | Trial completion date: Apr 2026 ➔ Dec 2026 | Trial primary completion date: Oct 2025 ➔ Oct 2026

Trial completion date • Trial primary completion date • Lung Cancer • Lung Non-Small Cell Squamous Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK • BRAF • EGFR • NTRK • PD-L1 • ROS1

Intravesical gemcitabine (Inlexzo) for bladder cancer. (PubMed, Med Lett Drugs Ther) - No abstract available

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

N-803 in Combination With Pembrolizumab and Enfortumab Vedotin for Treatment of Urothelial Cancer (clinicaltrials.gov) - P1 | N=18 | Not yet recruiting | Sponsor: Vadim S Koshkin

New P1 trial • Genito-urinary Cancer • Oncology • Solid Tumor • Urothelial Cancer

Male reproductive and sexual health outcomes following intravesical therapy for non-muscle invasive bladder cancer. (PubMed, World J Urol) - "With fatherhood increasingly occurring beyond age 40, uro-oncologists should consider the potential effects of intravesical therapy on male fertility and sexual function. Expanding research into reproductive outcomes among NMIBC patients may support more informed counseling on this matter."

HEOR • Journal • Review • Bladder Cancer • Genito-urinary Cancer • Infertility • Oncology • Sexual Disorders • Solid Tumor

N-803 and PD-L1 t-haNK Combined With Bevacizumab for Recurrent or Progressive Glioblastoma (clinicaltrials.gov) - P2 | N=34 | Recruiting | Sponsor: ImmunityBio, Inc. | Active, not recruiting ➔ Recruiting

Enrollment open • Brain Cancer • Glioblastoma • Oncology • Solid Tumor • PD-L1

First-in-class lymphocyte stimulating agent (LSA) nogapendekin alfa inbakicept (NAI) increases absolute lymphocyte count (ALC) in randomized trial in non-small cell lung cancer (NSCLC) (ESMO 2025) - P3 | "These data confirm the findings in normal healthy volunteers that NAI is the first cytokine fusion molecule in its class to treat lymphopenia. The potential of reversing lymphopenia induced by treatment, and prolonging survival, and improving prognosis across tumor types, may be a paradigm change in cancer care."

Clinical • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • CD4 • CD8 • IL15 • PD-L1

Clinical Trial of Ablation Therapy in Participants With Intermediate-Risk Non-Muscle Invasive Papillary Bladder Cancer (clinicaltrials.gov) - P2 | N=20 | Not yet recruiting | Sponsor: ImmunityBio, Inc. | Trial completion date: May 2029 ➔ Nov 2029 | Initiation date: May 2025 ➔ Nov 2025 | Trial primary completion date: May 2026 ➔ Nov 2026

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