Nogapendekin Alfa Inbakicept/CAR-NK Wins FDA RMAT Designation for Lymphopenia Reversal in Metastatic Pancreatic Cancer

The FDA has granted nogapendekin alfa inbakicept-pmln (Anktiva) and CAR-NK (PD-L1 t-haNK) regenerative medicine advanced therapy (RMAT) designation for the reversal of lymphopenia in patients treated with standard of care (SOC) chemotherapy/radiotherapy for multiple relapsed, locally advanced or metastatic pancreatic cancer, according to an announcement from ImmunityBio.1

The RMAT designation follows positive correlations of absolute lymphocyte count (ALC) and overall survival (OS) data from several QUILT trials evaluating patients with various tumor types, including patients receiving third-line or later treatment for metastatic pancreatic cancer (QUILT-88; NCT04390399), patients with immune checkpoint inhibitor–relapsed non–small cell lung cancer, and those requiring reversal of lymphopenia in multiple tumor types (QUILT-3.055; NCT03228667).

“RMAT designation for [nogapendekin alfa inbakicept] combined with NK cells was applied for by the founder in the initial 2017 IND [investigational new drug (application)]. With the clinical results of the QUILT trials across multiple tumor types from 2017 to 2024, validating the hypothesis that high-dose chemotherapy and radiation induces lymphopenia and can be reversed by [nogapendekin alfa inbakicept] together with off-the-shelf CAR-NK cells resulting in prolongation of OS, and enabling ImmunityBio to reapply for RMAT in 2025,” Patrick Soon-Shiong, MD, founder, executive chairman and global chief scientific and medical officer of ImmunityBio, stated in the announcement.

“[This] designation of [nogapendekin alfa inbakicept] and the first CAR-NK, both first-in-class molecules to activate lymphocytes within the body via subcutaneous injection of [nogapendekin alfa inbakicept] and via ex-vivo infusion of off-the-shelf PD-L1 NK cells, is an inflection point and a paradigm change of how we could treat patients with cancer and viral infections. The ALC which has been largely ignored by physicians, since no therapy existed to address lymphopenia, could now be both a prognostic biomarker but more importantly, the potential as a therapeutic biomarker.”

The IL-15 superagonist demonstrated reversal of lymphopenia and was consistent with the known mechanism of action of nogapendekin alfa inbakicept, showing proliferation and activation of NK cells, CD4+, CD8+, and memory T cells without the upregulation of suppressive T regulatory cells. A biologics license application (BLA) is intended to be submitted for the indication of the reversal of lymphopenia in patients treated with SOC chemotherapy with or without radiation therapy for the treatment of patients with locally advanced or metastatic pancreatic cancer with CAR-NK.

In April 2024, the FDA approved nogapendekin alfa inbakicept plus BCG for the treatment of adults with BCG-unresponsive non–muscle-invasive bladder cancer with carcinoma in situ with or without papillary tumors.2 Data from the phase 2/3 QUILT-3.032 trial (NCT0302285) supported the regulatory decision, demonstrating a complete response rate of 62% (95% CI, 51%-73%) in patients treated with the combination (n = 77).

“Multiple publications in the last five years have shown that patients with low lymphocyte counts, especially those with severe lymphopenia have a statistically lower survival rate regardless of the tumor types. With this RMAT designation and the attributes of a RMAT designation, including all breakthrough therapy designation features and statutory ways to support accelerated approval, we will move rapidly to file the BLA for these authorized indications provided by the RMAT designation,” Soon-Shiong continued in the announcement.1

“In addition, per the requirement under section 561A(f)(2) of the Federal Food, Drug, and Cosmetic Act (FD&C Act), ImmunityBio will make publicly available the Expanded Access Policy of [nogapendekin alfa inbakicept] and PD-L1 t-haNK in combination with SOC chemotherapy/radiotherapy within 15 days.”

References

1. ImmunityBio receives FDA RMAT designation for ANKTIVA and CAR-NK for the reversal of lymphopenia in patients receiving standard-of-care chemotherapy/radiotherapy and in treatment of multiply relapsed locally advanced or metastatic pancreatic cancer. News Release. ImmunityBio. February 27, 2025. Accessed March 5, 2025. https://immunitybio.com/immunitybio-receives-fda-rmat-designation-for-anktiva-and-car-nk-for-the-reversal-of-lymphopenia-in-patients-receiving-standard-of-care-chemotherapy-radiotherapy-and-in-treatment-of-multiply-rel/
2. FDA approves nogapendekin alfa inbakicept-pmln for BCG-unresponsive non–muscle invasive bladder cancer. FDA. April 22, 2024. Accessed March 5, 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-nogapendekin-alfa-inbakicept-pmln-bcg-unresponsive-non-muscle-invasive-bladder-cancer