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

NAI Plus Standard of Care Compared With Placebo Plus Standard of Care in Critically Ill Adults With Sepsis (clinicaltrials.gov) - P2 | N=50 | Not yet recruiting | Sponsor: ImmunityBio, Inc. | Phase classification: P1/2 ➔ P2 | Trial completion date: Dec 2027 ➔ Aug 2028 | Trial primary completion date: Oct 2027 ➔ May 2028

Phase classification • Trial completion date • Trial primary completion date • Infectious Disease • Septic Shock

Nogapendekin alfa inbakicept (NAI) and PD-L1 t-haNK plus bevacizumab (BEV) demonstrates lymphopenia reconstitution and disease control in recurrent Glioblastoma Multiform (rGBM) (ESMO 2026) - No abstract available

Lymphopenia • Brain Cancer • Glioblastoma • Hematological Malignancies • Oncology • Solid Tumor • PD-L1

Absolute lymphocyte count (ALC) and neutrophil-lymphocyte ratio (NLR) are prognostic biomarkers for OS across advanced solid tumors when Nogapendekin alfa inbakicept (NAI), an IL-15R Agonist, is added to SoC and following Checkpoint Inhibitor (CPI) Failure: Updates from QUILT-3.055 (ESMO 2026) - No abstract available

Biomarker • Checkpoint inhibition • Metastases • 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: ImmunityBio, Inc. | Trial completion date: May 2027 ➔ Jan 2032 | Initiation date: Feb 2026 ➔ Dec 2026 | Trial primary completion date: May 2027 ➔ Jan 2028

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

A Study to Examine Anktiva for the Treatment of COVID-19. (clinicaltrials.gov) - P2 | N=40 | Recruiting | Sponsor: ImmunityBio, Inc. | Trial completion date: Jul 2026 ➔ Mar 2027 | Trial primary completion date: Jul 2026 ➔ Mar 2027

Trial completion date • Trial primary completion date • Infectious Disease • Novel Coronavirus Disease

PT2.02. Metastatic NSCLC – Immunotherapy (IASLC-WCLC 2026) - "Additional presentations highlight innovative combination and next-generation approaches, including the PD-1/VEGF/CTLA-4 trispecific antibody HC010, tislelizumab plus SYS6010, the LIBRA platform study, the ROSETTA Lung-202 phase 3 trial of pumitamig versus pembrolizumab, and the ResQ1010 and ResQ201A trials evaluating nogapendekin alfa inbakicept and NAI-based regimens. Together with a randomized non-inferiority trial of denosumab dosing in bone metastases, these presentations offer a comprehensive view of the evolving therapeutic landscape and unmet needs in metastatic NSCLC immunotherapy."

IO biomarker • Metastases • Lung Cancer • Non Small Cell Lung Cancer • Solid Tumor • BRAF • CTLA4 • KEAP1 • KRAS • PD-1 • RET • STK11

Nogapendekin alfa inbakicept (NAI) and PD-L1 t-haNK plus bevacizumab (BEV) demonstrates disease control and rapid reconstitution of lymphocytes in recurrent glioblastoma (rGBM) (SNO 2026) - No abstract available

Brain Cancer • Glioblastoma • Solid Tumor • PD-L1

Final clinical results of pivotal trial of IL-15RαFc superagonist N-803 with BCG in BCG-unresponsive CIS and papillary nonmuscle-invasive bladder cancer (NMIBC). (ASCO 2022) - P2/3 | "Pembrolizumab was approved in 2020 with a 41% complete response (CR) rate in a single arm phase 2 trial of 96 patients. In 160 patients with BCG-unresponsive NMIBC, there is a 99% bladder cancer specific overall survival at 2 years. In CIS patients 71% CR rate with 24.1 months median duration of response, and 53% DFS rate at 18 months in Papillary disease. Cystectomy was avoided in over 90% of patients with 2 years of follow-up."

Clinical • Bladder Cancer • Fatigue • Genito-urinary Cancer • Oncology • Solid Tumor • Urothelial Cancer • CD8 • IL15

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

N-803 plus BCG Complete Response rate in NMIBC CIS subjects: BCG refractory, relapsed, checkpoint failure, and chemotherapy failure; updated results (QUILT 3.032) (AUA 2024) - P2/3 | "N-803 plus BCG results in a high CR rate in subjects who failed both BCG and other therapies, including additional BCG, chemotherapy and checkpoint inhibitors, with a median duration of response of >28 months."

Clinical • Bladder Cancer • CD8 • IL15

First-in-human evaluation of memory-like NK cells with an IL-15 super-agonist and CTLA-4 blockade in advanced head and neck cancer. (PubMed, J Hematol Oncol) - P1 | "CIML NK cells combined with N-803 and ipilimumab to treat head and neck cancer is safe, and associated with a more proliferative NK cell phenotype. However, the combination leads to reduced HLA mismatched NK cell persistence, resulting in an important limitation affecting NK cell combination therapies in clinical trials. These results inform evaluation of CIML NK therapy for advanced malignancies, with considerations for combination with IPI."

Journal • P1 data • Head and Neck Cancer • Oncology • Solid Tumor • CD8

Epigenetic plus cytokine therapy induces stem-like CD8+ T-cell reservoirs and intratumoral immune niches to overcome anti-PD-1 resistance. (PubMed, J Immunother Cancer) - "Treatment with entinostat, N-803, and αPD-1 boosts anti-tumor intratumoral immune niches comprising TCF1+CD8+ T cells. Collectively, these findings suggest that TCF1+CD8+ T cell immune niches previously associated with αPD-1 responsiveness and lacking in non-responders, including most CRC patients, may be restored by the addition of entinostat and N-803 to αPD-1 therapy to treat αPD-1-refractory patients."

IO biomarker • Journal • Breast Cancer • Colorectal Cancer • Oncology • Solid Tumor • CD8 • GZMB

Phase II evaluation of combination immunotherapy with CV301, N-803, bintrafusp alfa, and M9241 in patients with advanced small bowel and colorectal cancers. (ASCO-GI 2023) - P2 | "All patients had received prior 5-fluorouracil-based treatment, with 29/30 (96.7%) having received ≥ 2 lines of systemic therapy. Combination therapies with CV301, N-803, bintrafusp alfa, and M9241 had manageable safety profiles. Preliminary clinical activity was observed in patients with advanced MSS/pMMR small bowel or CRC. Median OS was promising as compared to historical median survivals of 6-7 months following receipt of multiple lines of therapy."

Clinical • Metastases • P2 data • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • IL12A • MUC1 • TGFB1

IL15 Superagonist (N-803, Anktiva) + Checkpoint Inhibitor (CPI) Prolongs OS in 2ndline or Greater NSCLC Patients Failing CPI (IASLC-WCLC 2024) - "QUILT 3.055, a phase 2b study of Anktiva in combination with CPI (nivolumab or pembrolizumab) in multiple tumor types including NSCLC who failed CPI. The KM curve demonstrates long-term survival at ≥18 and ≥21 months of 28/86 (33%) and 26/86 (30%) patients respectively: Conclusions : Anktiva plus CPI therapy in 2 nd line or greater NSCLC demonstrated long-term median OS, independent of PDL1 status, and independent of prior lines of therapy in patients with acquired resistance to CPI. These findings support the novel mechanism of action of Anktiva to rescue CPI activity through the activation of NK and T cells, driving long-term memory, with median OS ongoing survival of 33% and 30% at 18 and 21 months respectively, exceeding the standard of care."

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

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

ResQ201A: 2L+ Mnsclc ICI Failure: Randomized Phase 3 Trial of NAI + ICI + 2 Cycles Docetaxel vs Docetaxel (IASLC-WCLC 2026) - P2, P3 | "Nogapendekin alpha inbakicept (NAI) is a first-in-class IL-15 receptor agonist that induces proliferation and activation of natural killer cells, CD8+ T cells, and memory T cells without activating regulatory T cells, enhancing both the innate and adaptive immune systems to maximize immunogenic cell death. Exploratory analyses will be performed to meet study objectives. This trial has enrolled and treated participants."

Clinical • IO biomarker • P3 data • Immunology • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Solid Tumor • CD8 • IL15

An Update on QUILT-3.032: Complete Responses to N-803 plus BCG Therapy in BCG-Unresponsive Bladder Carcinoma In Situ (CIS) With or Without Ta/T1 Papillary Disease (AUA 2025) - P2/3 | "These findings derived from the fully-enrolled cohort A of QUILT 3.032, demonstrate the stability of the CR rate and confirm the durability of responses in participants with BCG-unresponsive bladder CIS +/- Ta/T1 papillary disease. They further demonstrate a positive association between achievement of a CR and both PFS and cystectomy avoidance. These updated results, together with previously reported safety and quality-of-life, indicate a favorable risk:benefit ratio for patients with bladder CIS +/- Ta/T1 papillary disease treated with N-803 plus BCG."

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

IL-15 trans-presentation at the innate-adaptive interface: mechanisms and translation in cancer immunotherapy. (PubMed, Oncoimmunology) - "Pharmacologic IL-15 receptor agonizts such as N-803 reproduce selected receptor-binding features of trans-presentation but do not reproduce its native source-cell, contact, or spatial restrictions...This narrative review synthesizes IL-15 receptor biology, innate and adaptive effector programs, counter-regulation, and clinical translation. It presents the 'innate bootstrap' as a mechanistic hypothesis: appropriately timed IL-15-axis engagement may strengthen an impaired innate-to-adaptive handoff, with efficacy determined by route, tissue context, partner therapy, exposure schedule, and patient selection."

Journal • Review • Bladder Cancer • Genito-urinary Cancer • Oncology • Solid Tumor • CD8 • FCGR2A • FCGR2B • IL12A • IL15 • IL18 • IL2 • IL2RA • IL2RG • ISG20 • PD-L1 • TGFB1 • TIGIT

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

ResQ1010-NSCLC: Phase 3 Study of Nogapendekin Alfa Inbakicept (NAI) + Standard of Care vs. SoC Alone in 1L Advanced/Metastatic NSCLC (ESMO 2026) - No abstract available

Metastases • P3 data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

ResQ108B-PANC: Open-Label, Phase 1 Clinical Trial of Neoadjuvant Nogapendekin Alfa Inbakicept, Sotevtamab, and Zabadinostat in Combination With Gemcitabine and Nab-Paclitaxel for Participants With Borderline Resectable or Locally Advanced Pancreatic Cancer (clinicaltrials.gov) - P1 | N=0 | Withdrawn | Sponsor: ImmunityBio, Inc. | N=30 ➔ 0 | Initiation date: Jun 2026 ➔ Sep 2026 | Not yet recruiting ➔ Withdrawn

Enrollment change • Trial initiation date • Trial withdrawal • Oncology • Pancreatic Cancer • Solid Tumor

QUILT-505: PD-L1 t-haNK, NAI IL-15sa and Cetuximab for Recurrent, Metastatic HNSCC (clinicaltrials.gov) - P2 | N=25 | Recruiting | Sponsor: Dana-Farber Cancer Institute | Trial primary completion date: Jul 2026 ➔ Dec 2026

Trial primary completion date • Head and Neck Cancer • Oncology • Oropharyngeal Cancer • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • PD-L1

NAI (Nogapendekin Alfa Inbakicept) Plus Standard of Care in Critically Ill Adults With Sepsis (clinicaltrials.gov) - P1/2 | N=49 | Not yet recruiting | Sponsor: ImmunityBio, Inc.

New P1/2 trial • Infectious Disease • Septic Shock

ResQ1010-NSCLC: Phase 3 Study of Nogapendekin Alfa Inbakicept+Standard of Care vs. Soc Alone in 1L Advanced Metastatic NSCLC (IASLC-WCLC 2026) - "Prior studies (QUILT-2.023) demonstrated that adding NAI to pembrolizumab was well-tolerated, significantly improved progression-free survival (PFS), and sustained ALC ≥1,000 cells/μL in patients with NSCLC, addressing and potentially reversing the challenge of lymphopenia during treatment...Methods : ResQ1010-NSCLC is a global, multicenter, Phase 3, randomized, open-label trial comparing NAI plus chemoimmunotherapy versus chemoimmunotherapy alone as first-line treatment for patients with stage IV squamous (CPI+platinum+taxane) or non-squamous (CPI+platinum+pemetrexed) NSCLC without actionable genomic alterations...Exploratory endpoints will aim to understand key biomarkers of response in this setting. ResQ1010-NSCLC aims to establish NAI as the first lymphocyte-stimulating agent to prevent treatment-induced lymphopenia and immune escape via MHC-loss or T-cell exhaustion, thereby enhancing first-line chemoimmunotherapy efficacy."

IO biomarker • Metastases • P3 data • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Solid Tumor • CD8 • IFNG • IL15 • PD-L1