On June 3, 2025 ImmunityBio, Inc. (NASDAQ: IBRX) reported results presented at ASCO (Free ASCO Whitepaper) 2025 of the first known treatment for lymphopenia with ANKTIVA and CAR-NK therapy (Press release, ImmunityBio, JUN 3, 2025, View Source [SID1234653673]). This data supports that reversal of lymphopenia, a well-established root cause of early mortality in patients with cancer across all tumor types, correlates with significant improved survival.

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While anemia and neutropenia have long been addressed by agents like Epogen and Neupogen, no therapy has ever existed for lymphopenia—until now. ANKTIVA (nogapendekin alfa inbakicept-pmln), an IL-15 superagonist approved in April 2024 for BCG-unresponsive non-muscle- invasive bladder cancer carcinoma in situ with or without papillary disease, represents the first lymphocyte-stimulating agent (LSA) capable of expanding lymphocytes critical for immunogenic cell death, such as natural killer (NK) and T cells.

These findings emphasize the need for a therapy to overcome treatment induced lymphopenia with higher mortality as presented at ASCO (Free ASCO Whitepaper) 2025 by several institutions (Abstract #8054, Satoskar et al. and Abstract #2663, Saleh et al.)

In a single-arm QUILT-88 clinical trial of 86 participants with third-to-sixth-line metastatic pancreatic cancer with very high tumor burden (CA19-9 levels exceeding 34,000 IU/ml), for which no therapy currently exists, patients received ANKTIVA subcutaneously in combination with off-the-shelf, ex-vivo infusion of CAR-NK cells (PD-L1 t-haNK) and low dose immuno-modulating chemotherapy. This first reported study of treating lymphopenia demonstrated significant differences in median overall survival in subjects whose lymphopenia was reversed (Absolute Lymphocyte Count: ALC ≥ 1,000).

In 67 out of 86 subjects, reversal of lymphopenia was achieved and median overall survival was significantly prolonged compared to those who remained in severe lymphopenia with P-value 0.005, HR: 0.46 (0.26, 0.80) in Figure 1. In subjects with lymphopenia rescue and a lower tumor burden (less than the median CA19-9 of 34,000 IU/mL), the median overall survival in these very advanced metastatic pancreatic cancer patients exceeded 10 months (Figure 2).

These findings of improved survival in pancreatic cancer patients with lower tumor burden point to the potential of further prolonged overall survival in pancreatic cancer patients if treated in the first line or neoadjuvant stages of disease. 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 in a 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—remained in remission for over six years and maintains a high quality of life at the date of this release.

The expanded access authorization announced yesterday enables patients across all solid tumor types who have exhausted first-line therapy including chemotherapy, radiation, or immunotherapy to receive Anktiva as a lymphocyte stimulating agent to protect the immune system from the lymphogenic adverse effects of current standards of care.

The ASCO (Free ASCO Whitepaper) Annual Meeting 2025 materials from ImmunityBio 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

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 levels are laboratory measurements that have been extensively reported as predictive biomarkers of poor prognosis with early mortality across all tumor types5,6. The data presented by ImmunityBio for the first time demonstrates that improving ALC and NLR correlates with significant enhanced overall survival and clinical benefit.

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 EPO 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 types5. 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 cells7.

More information on lymphopenia could be found on Twitter/X @DrPatSoonShiong articles here: View Source