On June 2, 2025 ImmunityBio, Inc. (NASDAQ: IBRX), a leading immunotherapy company, reported that the U.S. Food and Drug Administration (FDA) has granted Expanded Access authorization for the use of its Cancer BioShield platform, anchored by ANKTIVA (nogapendekin alfa inbakicept-pmln), to treat lymphopenia in adult patients with refractory or relapsed solid tumors independent of tumor type who have progressed after first-line standard-of-care treatment, chemotherapy, radiation, or immunotherapy (Press release, ImmunityBio, JUN 2, 2025, View Source [SID1234653609]).
Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:
Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing
Schedule Your 30 min Free Demo!
To date no treatment exists for lymphopenia, a depletion of critical lymphocytes responsible for immunogenic cell death, specifically natural killer (NK) cells, killer CD8+ T cells and CD4+ with memory T cells. Treatment induced lymphopenia is a debilitating consequence of chemotherapy, radiation, and certain immunotherapies and steroids. This treatment-acquired immunodeficiency not only increases susceptibility to infections but also deprives the body’s immune system to fight residual or recurrent cancer, accelerating metastasis and disease progression, and contributing to early mortality. Countless publications over the last two decades has reported lymphopenia as a highly predictive biomarker of poor prognosis across all tumor types.1-6 Despite its significant clinical impact, the pharmaceutical industry has largely overlooked lymphopenia as a disease in its own right, and no approved therapies have existed to directly address it, until the approval of ANKTIVA in the treatment of BCG-unresponsive bladder cancer with the mechanism of action of an IL-15 superagonist proliferating key lymphocytes.7
While oncologists and patients have long had therapies such as EPOGEN and NEUPOGEN to manage chemotherapy- and radiation-induced anemia and neutropenia, no comparable option has been available for lymphopenia. ANKTIVA, an interleukin-15 (IL-15) agonist, is the first approved therapy with a defined mechanism of action to restore lymphocyte levels. It activates and proliferates NK and T cells without inducing immunosuppressive regulatory T cells (Tregs), offering the first solution for reversing this critical immune deficit of lymphocytes in cancer patients.7
"Lymphopenia has long been recognized as a major driver and predictor of early mortality in cancer—yet until now, it has remained unaddressed," said Dr. Patrick Soon-Shiong, Founder, Executive Chairman and Global Chief Scientific and Medical Officer of ImmunityBio. "This FDA authorization allows all patients with solid tumors suffering from immune collapse following first-line therapy of chemo, radiation, or immunotherapy to access ANKTIVA. The survival benefit we observed at ASCO (Free ASCO Whitepaper) 2025 in 3rd to 6th line advanced metastatic pancreatic cancer confirms that restoring lymphocyte levels—rather than depleting them—can change the course of disease."
At the 2025 ASCO (Free ASCO Whitepaper) Annual Meeting, ImmunityBio presented landmark results showing that reversing lymphopenia with ANKTIVA and CAR-NK therapy significantly prolonged median overall survival in third- to sixth-line metastatic pancreatic cancer patients. This benefit was further enhanced when treatment began at lower tumor burdens, as indicated by CA19-9 levels. Highlighting the importance of lymphopenia reversal, Oncologist published a peer-reviewed paper titled "Recurrent pancreatic cancer treated with N-803 and PD-L1 t-haNK followed by an EGFR-targeted nanocell drug conjugate," demonstrating that the patient with 2nd line metastatic pancreatic cancer treated with the full Cancer BioShield platform—including ANKTIVA, CAR-NK cells (PD-L1 t-haNK), and antigen-targeting adenoviruses—has remained in remission for over six years and maintains a high quality of life at the date of this release.
"We are entering a new era in oncology where the goal is not only to target the tumor but to protect and empower the immune system itself," continued Dr. Soon-Shiong. "Through this Expanded Access Program, we can now offer hope to patients with solid tumors who have exhausted standard options. Our mission is to transform cancer care by reversing the immune collapse that often leads to progression and mortality by enabling the body to serve as a factory for the regeneration and reconstitution of the lymphocytes key to immunogenic cell death of the tumor. By mitigating treatment induced lymphopenia from our standards of care, ANKTIVA can serve as a Cancer Bioshield."
In February 2025, ImmunityBio announced it had received a Regenerative Medicine Advanced Therapy (RMAT) designation from the FDA for ANKTIVA and CAR-NK (PD-L1 t-haNK) for the reversal of lymphopenia in patients receiving standard-of-care chemotherapy/radiotherapy and in relapsed locally advanced or metastatic pancreatic cancer. The RMAT designation is intended to expedite the development of therapies targeting serious or life-threatening conditions with unmet medical need.
Full results of our 2025 ASCO (Free ASCO Whitepaper) Annual Meeting can be found below:
Association of lymphopenia rescue and CA19-9 levels with overall survival following IL-15 superagonist N-803 and PD-L1 t-haNK chemo-immunotherapy for 3rd line or greater metastatic pancreatic cancer.
Abstract Text: View Source
Poster PDF: View Source
QUILT 3.076 phase 1 study of memory-like cytokine-enriched natural killer (M-CENK) cells plus N-803 in locally advanced or metastatic solid tumors.
Abstract Text: View Source
Poster PDF: View Source
About the Cancer BioShield Platform
The Cancer BioShield platform is a first-in-class immunotherapy strategy designed to restore immune competence by reversing lymphopenia—the loss of functional immune cells caused by cancer itself and by conventional treatments such as chemotherapy, radiation and immunotherapy. At its core is ANKTIVA (nogapendekin alfa inbakicept-pmln), an IL-15 agonist approved for BCG-unresponsive non–muscle-invasive bladder cancer CIS with or without papillary disease, activates and proliferates natural killer (NK) cells and CD4+ and CD8+ T cells, restoring lymphocyte levels critical for immunosurveillance, immunogenic cell death, and long-term tumor control.
The platform employs a multi-modal approach:
In-vivo stimulation: Subcutaneous administration of ANKTIVA expands NK and T cells, boosting anti-tumor immunity.
Ex-vivo targeted cytotoxicity: Off-the-shelf PD-L1 t-haNK CAR-NK cells are engineered to target and eliminate PD-L1–expressing tumor cells and immunosuppressive neutrophils (myeloid-derived suppressor cells), enhancing anti-tumor specificity and reducing immune evasion.
Memory Cytokine-Enriched Natural Killer (M-ceNK) cell therapy: M-ceNK cells are developed via cytokine activation and expansion of autologous and allogeneic NK cells collected through apheresis, potentially providing long-term immune memory and sustained cytotoxic capacity.
Together, these components offer a comprehensive, novel, immune-restoring therapeutic platform aimed at not only expanding effector immune cells, but also overcoming tumor-mediated immune suppression to support long-term disease control.
The platform’s effectiveness can be tracked through universally utilized simple complete blood count (CBC): increases in absolute lymphocyte count (ALC) reflect ANKTIVA’s lymphocyte-stimulating activity, while reductions in the neutrophil-to-lymphocyte ratio (NLR) demonstrate PD-L1 t-haNK’s immunosuppressive neutrophil targeting. Low ALC and high NLR levels6 are laboratory measurements that have been extensively reported as predictive biomarkers of poor prognosis with early mortality across all tumor types.1-6 The data presented by ImmunityBio for the first time demonstrates that improving ALC and NLR correlates with significant enhanced overall survival and clinical benefit.
With potential applications extending beyond oncology—including infectious disease, sepsis, and immune senescence—the Cancer BioShield Platform represents a potentially transformative shift in treating not just the tumor, but the underlying immune collapse that allows disease to progress.
About Lymphopenia and Absolute Lymphocyte Count (ALC)
Lymphopenia—the loss of key immune cells such as NK, CD4+, and CD8+ T cells—is a common side effect of chemotherapy1, radiation2,3, and some immunotherapies4. Unlike anemia and neutropenia, which have FDA-approved treatments like EPOGEN and NEUPOGEN, no therapy previously existed to treat this immune cell depletion. Lymphopenia weakens the immune system, increases infection risk, and is linked to early death across many cancer types.1-6 Low Absolute Lymphocyte Count (ALC) is a recognized poor prognostic marker. ANKTIVA is the first approved therapy to restore lymphocyte levels by activating and expanding NK and T cells—without increasing immunosuppressive T regulatory cells.