PD-L1.t-haNK / ImmunityBio - LARVOL DELTA

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

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

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

Phase II Trial of Neoadjuvant (NA) Pembrolizumab + N-803 alone or in combination with PD-L1 t-haNK Cells for Resectable Head and Neck Squamous Cell Carcinoma (HNSCC) (MHNCS 2026) - P2 | "TBD"

Clinical • Combination therapy • IO biomarker • P2 data • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • CD8 • IL15 • IL2 • PD-L1

QUILT-3.078: 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

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

Response in first-in-human chemotherapy-free combination immunotherapy targeting lymphopenia in recurrent glioblastoma multiform (GBM): Nogapendekin alfa inbakicept (NAI) and PD-L1 t-haNK plus bevacizumab (BEV). (ASCO 2026) - P2 | " Phase 2 QUILT-3.078 trial (NCT06061809) of participants with GBM (IDH WT) who recurred after surgery and temozolomide/XRT. These findings support that reconstituting lymphocytes (NK & T cells) results in response, including complete response, in recurrent GBM. This is the first report of disease response in participants with recurrent GBM who received orchestrated systemic immunotherapy with CAR-NK cells combined with an IL-15 agonist and BEV. The potential of reversing lymphopenia induced by SOC treatment, prolonging survival, and improving prognosis across tumor types, may be a paradigm change in cancer care."

First-in-human • Lymphopenia • P1 data • Brain Cancer • CNS Disorders • Giant Cell Arteritis • Glioblastoma • Hematological Malignancies • Immunology • Pulmonary Embolism • Respiratory Diseases • Solid Tumor • IL15 • PD-L1

Immunotherapy Combination: Irradiated PD-L1 CAR-NK Cells Plus Pembrolizumab Plus N-803 for Subjects With Recurrent/Metastatic Gastric or Head and Neck Cancer (clinicaltrials.gov) - P2 | N=18 | Completed | Sponsor: National Cancer Institute (NCI) | Active, not recruiting ➔ Completed | Trial completion date: Dec 2027 ➔ Jan 2026 | Trial primary completion date: Jan 2027 ➔ Dec 2025

Trial completion • Trial completion date • Trial primary completion date • Esophageal Cancer • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma of Head and Neck • PD-L1

Phase 2 Study of NAI, HPV Vaccine, and Nab-Paclitaxel in HPV-Positive Oropharyngeal Cancer Followed by De-Intensified Radiation Compared With Standard Chemoradiation (clinicaltrials.gov) - P2 | N=70 | Not yet recruiting | Sponsor: ImmunityBio, Inc.

New P2 trial • Brain Cancer • Glioblastoma • Head and Neck Cancer • Oncology • Oropharyngeal Cancer • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

Improved natural killer cell targeting of prostate carcinoma with ATR inhibitor tuvusertib in combination with IL-15 receptor superagonist N-803 (IMMUNOLOGY 2026) - "Tuvusertib rendered PCa cells more susceptible to NK-mediated lysis and PD-L1-targeting by avelumab-mediated antibody-dependent cellular cytotoxicity (ADCC) and PD-L1 t-haNK cells. Immune-mediated targeting of prostate carcinoma is improved by tuvusertib ATRi which can be combined with avelumab and/or N-803."

Combination therapy • IO biomarker • Ataxia • Genito-urinary Cancer • Immunology • Movement Disorders • Oncology • Primary Immunodeficiency • Prostate Cancer • Solid Tumor • IL15 • TNFRSF10B

Immunogenic modulation with the ATR inhibitor tuvusertib enhances NK-mediated killing of prostate cancer [WITHDRAWN] (AACR 2025) - "Furthermore, tuvusertib treatment increased PD-L1 expression on the DU145 cells, which is associated with enhanced donor NK killing in the presence of avelumab and augmented sensitivity to PD-L1 t-haNK cells.Next, the anti-tumor effect of combining tuvusertib with N-803 (provided by ImmunityBio, Culver City, CA, USA) was investigated. Furthermore, tuvusertib synergized with N-803, resulting in a superior anticancer response. This provides a rationale for further investigation of this combination therapy."

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

Generation of cytokine-induced memory-like PD-L1 t-haNK (NK-92®) cells (AACR 2025) - "We show here that the Natural Killer cell line NK-92®, or 'activated' NK (aNKTM), can acquire a memory-like phenotype upon overnight induction with IL-12, IL-18, and the IL-15 superagonist N-803, as evidenced by increased steady-state IFNγ secretion (>50-fold increase) and up-regulation of CD25. This increase would then drive upregulation of PD-L1 expression on neighboring tumor cells, creating an expanding wave of targets sensitized to killing by PD-L1 t-haNK cells. A next generation, memory-like PD-L1 t-haNK cell line equipped with inducible safety switch features to remove the need for irradiation and extend their half-life in patients is being developed and would constitute a promising "off-the-shelf" cellular therapy against immunologically cold cancers."

IO biomarker • Oncology • IFNG • IL12A • IL18 • IL2RA • PD-L1

QUILT 3.064: QUILT-3.064: PD-L1 t-haNK In Subjects With Locally Advanced Or Metastatic Solid Cancers (clinicaltrials.gov) - P1 | N=16 | Completed | Sponsor: ImmunityBio, Inc. | Active, not recruiting ➔ Completed

Trial completion • Oncology • Solid Tumor • PD-L1

QUILT 3.064: QUILT-3.064: PD-L1 t-haNK In Subjects With Locally Advanced Or Metastatic Solid Cancers (clinicaltrials.gov) - P1 | N=16 | Active, not recruiting | Sponsor: ImmunityBio, Inc. | Trial completion date: Nov 2025 ➔ Mar 2026 | Trial primary completion date: Nov 2025 ➔ Mar 2026

Trial completion date • Trial primary completion date • Oncology • Solid Tumor • PD-L1

The ATR inhibitor tuvusertib (M1774) sensitizes prostate carcinoma to natural killer cell-mediated cytotoxicity, which is further augmented by the IL-15 receptor superagonist N-803. (PubMed, Cancer Immunol Immunother) - "Enhanced avelumab-mediated antibody-dependent cell-mediated cytotoxicity and lysis by PD-L1 targeting high-affinity NK (PD-L1 t-haNK) cells were observed in tuvusertib-treated DU145. In vivo in the DU145 PCa xenograft model, tuvusertib and N-803 combination therapy demonstrated marked and significant antitumor efficacy relative to either monotherapy, eliciting superior tumor growth control and prolonging survival. Our findings support further investigation into the use of ATRi with immune checkpoint blockade and/or immune-stimulating agents in prostate cancer."

Journal • Ataxia • Genito-urinary Cancer • Immunology • Movement Disorders • Oncology • Primary Immunodeficiency • Prostate Cancer • Solid Tumor • BCL2L1 • CDKN1A • IL15 • NKG2D • TNFRSF10B

QUILT-88: Combination Immunotherapy Plus Standard-of-Care Chemotherapy Versus Standard-of-Care Chemotherapy for the Treatment of Locally Advanced or Metastatic Pancreatic Cancer (clinicaltrials.gov) - P2 | N=328 | Active, not recruiting | Sponsor: ImmunityBio, Inc. | Trial completion date: Oct 2025 ➔ May 2026

Trial completion date • Oncology • Pancreatic Cancer • Solid Tumor

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

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

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

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

QUILT 3.064: QUILT-3.064: PD-L1 t-haNK In Subjects With Locally Advanced Or Metastatic Solid Cancers (clinicaltrials.gov) - P1 | N=16 | Active, not recruiting | Sponsor: ImmunityBio, Inc. | Trial completion date: Dec 2024 ➔ Nov 2025 | Trial primary completion date: Oct 2024 ➔ Nov 2025

Trial completion date • Trial primary completion date • Oncology • Solid Tumor • PD-L1

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

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

Pembrolizumab + N-803 Alone or in Combination With PD-L1 t-haNK Cells for Resectable Head and Neck Squamous Cell Carcinoma (clinicaltrials.gov) - P2 | N=40 | Recruiting | Sponsor: National Cancer Institute (NCI) | Not yet recruiting ➔ Recruiting | Trial completion date: Dec 2027 ➔ Dec 2028 | Trial primary completion date: Dec 2025 ➔ Dec 2026

Enrollment open • Trial completion date • Trial primary completion date • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

QUILT-505: PD-L1 t-haNK, N-803 IL-15sa and Cetuximab for Recurrent, Metastatic HNSCC (clinicaltrials.gov) - P2 | N=25 | Recruiting | Sponsor: Glenn J. Hanna | Trial primary completion date: Jul 2025 ➔ Jul 2026

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

Immunotherapy Combination: Irradiated PD-L1 CAR-NK Cells Plus Pembrolizumab Plus N-803 for Subjects With Recurrent/Metastatic Gastric or Head and Neck Cancer (clinicaltrials.gov) - P2 | N=18 | Active, not recruiting | Sponsor: National Cancer Institute (NCI) | Recruiting ➔ Active, not recruiting | N=55 ➔ 18

Enrollment change • Enrollment closed • Esophageal Cancer • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma of Head and Neck • PD-L1