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

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 GBM Phase I QUILT-3.078 trial of participants with GBM (IDH WT) who recurred after surgery and temozolomide/XRT... These findings provide support that treating lymphopenia and reconstituting lymphocytes (NK & T cells) results in potential OS benefit. 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

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

A Phase II Study With a Safety Run-In of the Addition of N-803 to a Chemoimmunotherapy Backbone for the Treatment of Patients With Relapsed or Refractory Neuroblastoma (clinicaltrials.gov) - P2 | N=54 | Recruiting | Sponsor: St. Jude Children's Research Hospital | Not yet recruiting ➔ Recruiting

Enrollment open • Neuroblastoma • Oncology • Solid Tumor • CSF2

Mechanisms, Clinical Trials, and New Treatments for BCG-Unresponsive in Nonmuscle Invasive Bladder Cancer. (PubMed, Cancer Med) - "The treatment landscape for BCG-unresponsive NMIBC is rapidly evolving, with immune checkpoint inhibitors, gene therapies, targeted agents, and advanced drug delivery systems showing promising efficacy. These innovations provide bladder-preserving options for patients ineligible for radical cystectomy. Future directions include biomarker-driven therapy selection, combination regimens, and optimized intravesical delivery platforms to improve long-term outcomes."

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

Traditional and next-generation bacillus Calmette-Guérin based treatment strategies for bacillus Calmette-Guérin unresponsive non-muscle-invasive bladder cancer in the era of emerging therapies. (PubMed, Curr Opin Urol) - "Despite its limited efficacy as monotherapy in unresponsive cases, BCG retains therapeutic relevance as part of combination strategies that enhance its immunologic activity. Emerging data suggest that these BCG-based regimens offer a promising, bladder-sparing alternative for patients who are ineligible for or decline radical cystectomy. Ongoing and future trials will be essential to define optimal combinations and identify which patients are most likely to benefit, thereby enabling appropriate patient selection."

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

QUILT-3.055: A Study of Combination Immunotherapies in Patients Who Have Previously Received Treatment With Immune Checkpoint Inhibitors (clinicaltrials.gov) - P2 | N=40 | Active, not recruiting | Sponsor: ImmunityBio, Inc. | Recruiting ➔ Active, not recruiting

Checkpoint inhibition • Enrollment closed • Cervical Cancer • Colorectal Cancer • Esophageal Cancer • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Genito-urinary Cancer • Head and Neck Cancer • Hepatocellular Cancer • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Melanoma • Merkel Cell Carcinoma • Microsatellite Instability • Non Small Cell Lung Cancer • Oncology • Renal Cell Carcinoma • Skin Cancer • Small Cell Lung Cancer • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • Urothelial Cancer • ALK • BRAF • MSI

Cytokine Induced Memory-like NK Cell Adoptive Therapy After Haploidentical Donor Hematopoietic Cell Transplantation (clinicaltrials.gov) - P2 | N=60 | Active, not recruiting | Sponsor: Washington University School of Medicine | Recruiting ➔ Active, not recruiting | Trial completion date: Jan 2027 ➔ Sep 2026 | Trial primary completion date: Jan 2027 ➔ Sep 2026

Enrollment closed • Trial completion date • Trial primary completion date • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • Transplantation

N-803 and PD-L1 t-haNK Combined With Bevacizumab for Recurrent or Progressive Glioblastoma (clinicaltrials.gov) - P2 | N=34 | Active, not recruiting | Sponsor: ImmunityBio, Inc. | Recruiting ➔ Active, not recruiting | N=20 ➔ 34

Enrollment change • Enrollment closed • Brain Cancer • Glioblastoma • Oncology • Solid Tumor • PD-L1

Phase 3 Clinical Trial ResQ201A of N-803 (NAI), Tislelizumab and Docetaxel Vs. Docetaxel Monotherapy for Advanced NSCLC Resistant to ICI Therapy (IASLC-WCLC 2025) - P3 | "Important assessments are changes in the tumor size, if any, and how long it lasts, referred to as the disease control rate, the objective response rate, and progression-free survival. Determination of safety is very important, therefore vital signs and changes in laboratory tests will be recorded, as well as adverse events (AEs) of all severity using the NCI CTCAE v5.0 system."

Clinical • IO biomarker • Metastases • Monotherapy • P3 data • Bladder Cancer • Esophageal Cancer • Genito-urinary Cancer • Immunology • Lung Cancer • Non Small Cell Lung Cancer • Small Cell Lung Cancer • Solid Tumor • ALK

Phase 3 Trial ResQ201A of NAI Plus Tislelizumab and Docetaxel Vs. Docetaxel Monotherapy for Advanced or Metastatic NSCLC Resistant to ICI Therapy (IASLC-WCLC 2025) - P3 | "2024; 19(10) Suppl.] have demonstrated the potential for the IL-15 receptor superagonist nogapendekin alfa inbakicept (NAI; or N-803) as a novel lymphocyte stimulating agent (LSA) to enhance ICI efficacy, prolonging progression-free survival (PFS) and overall survival (OS) when used in combination with an ICI. Secondary efficacy endpoints are the immune disease control rate (iDCR - iCR + iPR + iSD [≥ 2 months]) per iRECIST; progression-free survival (iPFS), overall response rate (iORR) and duration of response (iDOR). Safety is assessed by AEs and SAEs graded using the NCI CTCAE v5.0."

Metastases • Monotherapy • P3 data • Immunology • Lung Cancer • Non Small Cell Lung Cancer • Solid Tumor • ALK • IL15

NAI, An IL-15 Superagonist, A New Class Of Lymphocyte Stimulating Agent (LSA) Prolongs OS In NSCLC By Reversing Lymphopenia (IASLC-WCLC 2025) - P2 | "Introduction : Prior to the approval of Nogapendekin alfa inbakicept (NAI), an IL-15 superagonist which stimulates lymphocytes important in immunogenic cell death (Natural killer cells, CD4+ CD8+ T cells and memory T cells), no treatment existed to address lymphopenia as measured by the absolute lymphocyte count (ALC) in the CBC differential...Lymphopenia is addressed for the first time with availability of this new class of lymphocyte stimulating agent (LSA), NAI. When ALC is maintained ≥1,500 with NAI, the immune system is effectively activated (chemo-free), and median OS is significantly prolonged at 21.1 months, HR: 0.33 (95% CI:0.16,0.65) P=0.0009."

IO biomarker • Lymphopenia • Febrile Neutropenia • Hematological Malignancies • Lung Cancer • Non Small Cell Lung Cancer • Solid Tumor • CD4 • CD8

Prolonged Progression-Free Survival, Disease-Free Survival and Cystectomy Avoidance with IL-15 Receptor Lymphocyte-Stimulating Agent NAI plus BCG in BCG-Unresponsive Papillary-Only NMIBC. (PubMed, J Urol) - P2/3 | "In QUILT-3.032, the efficacy of IL-15 receptor agonist, nogapendekin alfa inbakicept (NAI) in combination with BCG for BCG-unresponsive high-grade papillary-only non-muscle invasive bladder cancer (NMIBC) was assessed...Most TRAEs were grade 1-2 (61%) with 3% grade 3, and no grade 4-5. The 12- and 36-month DFS, PFS, DSS, and cystectomy avoidance rates demonstrate the effectiveness and safety of NAI plus BCG in the management of BCG-unresponsive papillary disease."

Journal • Bladder Cancer • Genito-urinary Cancer • Oncology • Solid Tumor • IL15