ImmunityBio’s ANKTIVA: A Paradigm Shift in Glioblastoma Treatment with 100% Disease Control in Early Trials

In the battle against glioblastoma (GBM), a cancer with a historically dismal five-year survival rate of less than 10% for patients over 45 [1], ImmunityBio’s ANKTIVA has emerged as a potential game-changer. Recent phase 2 trial data (NCT06061809) revealed a staggering 100% disease control rate in five patients with second-line recurrent GBM treated with a chemotherapy-free regimen combining ANKTIVA (nogapendekin alfa inbakicept-pmln), natural killer (NK) cell therapy (PD-L1 t-haNK), and Optune Gio tumor-treating fields [1]. Three patients achieved near-complete responses, while two experienced stable disease—a result that challenges conventional wisdom about the intractability of GBM.

The Science Behind the Breakthrough

ANKTIVA, an IL-15 superagonist, works by activating and proliferating NK cells, CD4+ T cells, CD8+ T cells, and memory T cells without triggering suppressive regulatory T cells [3]. This mechanism is critical in reversing lymphopenia—a condition marked by low lymphocyte counts that often follows standard-of-care radiation and chemotherapy. In the trial, ANKTIVA increased absolute lymphocyte counts (ALC) in all five patients who had previously experienced lymphopenia [1]. By restoring immune function, the therapy creates a favorable environment for NK cell therapy to target tumor cells, while Optune Gio’s electric fields disrupt cancer cell division.

The combination’s success lies in its ability to address GBM’s dual challenges: immune suppression and tumor heterogeneity. Traditional therapies like temozolomide and radiation often fail to penetrate the blood-brain barrier or sustain long-term immune activation. ANKTIVA’s approach, however, leverages the body’s own immune system to create a durable antitumor response.

Regulatory Momentum and Market Potential

ImmunityBio’s regulatory strategy has accelerated alongside its clinical progress. In February 2025, the FDA granted Regenerative Medicine Advanced Therapy (RMAT) designation for ANKTIVA in combination with CAR-NK for reversing lymphopenia and treating pancreatic cancer [3]. RMAT status enables expedited development and potential accelerated approval, a critical advantage for a therapy targeting a high-unmet-need indication.

The company has also submitted an Expanded Access Protocol (EAP) to the FDA for ANKTIVA, allowing early access for patients with solid tumors [2]. This move underscores ImmunityBio’s intent to position ANKTIVA as a “BioShield” against the adverse effects of standard cancer treatments—a narrative that could attract both investors and clinicians.

Investment Implications

The financial stakes are enormous. GBM affects approximately 12,000 patients annually in the U.S. alone, with second-line treatment options limited and costly [1]. A chemotherapy-free regimen that achieves 100% disease control could redefine standards of care, particularly if larger trials replicate these results. ImmunityBio’s planned phase 2 trial for second-line GBM will be a pivotal test, but the early data already suggest a path to commercialization.

Moreover, ANKTIVA’s dual role in reversing lymphopenia opens a secondary market. Lymphopenia is a common side effect of cancer treatments, contributing to early mortality and increased infection risk. By addressing this unmet need, ANKTIVA could generate revenue streams beyond GBM, including in pancreatic cancer and other solid tumors.

Risks and Considerations

While the data are promising, investors must remain cautious. The trial’s small sample size (n=5) and lack of long-term follow-up data mean larger trials are essential to validate these results. Additionally, the cost of manufacturing NK cell therapy and Optune devices could pose scalability challenges. However, the RMAT designation and FDA’s Expanded Access Program provide a framework to mitigate these risks through regulatory support and early patient access.

Conclusion

ImmunityBio’s ANKTIVA represents a rare convergence of scientific innovation and regulatory momentum. By achieving 100% disease control in a chemotherapy-free regimen for recurrent GBM—a cancer with no effective second-line treatments—the therapy has the potential to disrupt a $10 billion market. For investors, the key question is not whether ANKTIVA can work, but whether ImmunityBio can scale its production and navigate the regulatory landscape to bring this breakthrough to patients.

Source:[1] ImmunityBio. (2025). Initial Data Shows 100% Disease Control in 5 Out of 5 Patients With Recurrent Glioblastoma. https://immunitybio.com/initial-data-shows100-disease-control-in-5-out-of-5-patients-with-recurrent-glioblastoma-with-two-patients-in-near-complete-response-treated-with-immunitybios-anktiva-nk-cell-therapy-p/[2] ImmunityBio. (2025). FDA Submissions of Expanded Access of ANKTIVA to Treat Lymphopenia. https://immunitybio.com/immunitybio-announces-fda-submissions-of-supplemental-bla-for-nmibc-papillary-disease-and-for-expanded-access-of-anktiva-to-treat-lymphopenia/[3] BusinessWire. (2025). FDA RMAT Designation for ANKTIVA and CAR-NK. https://www.businesswire.com/news/home/20250227880542/en/ImmunityBio-Receives-FDA-RMAT-Designation-for-ANKTIVA-and-CAR-NK-for-the-Reversal-of-Lymphopenia-in-Patients-Receiving-Standard-of-Care-ChemotherapyRadiotherapy-and-in-Treatment-of-Multiply-Relapsed-Locally-Advanced-or-Metastatic-Pancreatic-Cancer