FDA Grants RMAT Designation to Nogapendekin Alfa in Pancreatic Cancer
The FDA granted RMAT designation to nogapendekin alfa and CAR-NK for reversing lymphopenia in patients with cancer, with promising survival data in metastatic pancreatic cancer and non–small cell lung cancer.
US FDA
- The FDA granted Regenerative Medicine Advanced Therapy (RMAT) status to nogapendekin alfa (Anktiva) and CAR-NK (PD-L1 t-haNK) for reversing lymphopenia in patients undergoing chemotherapy/radiotherapy and treating metastatic pancreatic cancer.
- Significant overall survival (OS) correlations were observed in QUILT trials across multiple tumor types, including metastatic pancreatic cancer and non–small cell lung cancer (NSCLC).
- ImmunityBio plans to submit a biologic license application (BLA) for lymphopenia reversal and pancreatic cancer treatment.
The FDA has granted RMAT designation to nogapendekin alfa and CAR-NK for the reversal of lymphopenia in patients receiving standard-of-care chemotherapy or radiotherapy, as well as for the treatment of multiply relapsed locally advanced or metastatic pancreatic cancer.1
This RMAT designation follows robust clinical data demonstrating that nogapendekin alfa, an IL-15 superagonist, reverses lymphopenia by proliferating and activating NK cells, CD4+ T cells, CD8+ T cells, and memory T cells without upregulating suppressive T regulatory cells.1 This mechanism is consistent with the drug’s label and has shown significant correlations with improved OS in patients with metastatic pancreatic cancer, checkpoint-relapsed NSCLC, and other tumor types.
Additionally, the designation is based on compelling clinical data from the QUILT trials, which span multiple tumor types. Findings from the trial have revealed that absolute lymphocyte count (ALC) is a critical prognostic biomarker.
“RMAT designation for [nogapendekin alfa] combined with NK cells was applied for by the Founder in the initial 2017 [investigational new drug]. 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] together with off-the-shelf CAR-NK cells (PD-L1 t-haNK) resulting in prolongation of OS, and enabling ImmunityBio to reapply for RMAT in 2025,” said Patrick Soon-Shiong, MD, founder, executive chairman and global chief scientific & medical officer of ImmunityBio, in a press release.
Microscopic image of pancreatic cancer cells - Generated with Google Gemini AI
With this, a BLA for nogapendekin alfa and CAR-NK is planned to be submitted for the reversal of lymphopenia in patients undergoing standard-of-care chemotherapy or radiotherapy and for the treatment of patients with locally advanced or metastatic pancreatic cancer.
Additionally, the company plans to release an expanded access policy within 15 days, allowing eligible patients to access nogapendekin alfa and PD-L1 t-haNK in combination with standard therapies.
With RMAT designation, ImmunityBio gains access to accelerated approval pathways, including breakthrough therapy designation features. The company also is expected to present comprehensive data from its QUILT trials, including metastatic pancreatic cancer (QUILT-88; NCT04390399) and checkpoint-relapsed NSCLC (QUILT-3.055; NCT03228667), at upcoming medical conferences.
The FDA previously granted nogapendekin alfa approval when given with Bacillus Calmette-Guérin (BCG) in patients with BCG-unresponsive non–muscle-invasive bladder cancer carcinoma in situ, on April 22, 2024.2
“[This] designation of [nogapendekin alfa] and the first CAR-NK (PD-L1 T-haNK), both first-in-class molecules to activate lymphocytes within the body (via subcutaneous injection of [nogapendekin alfa]) 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,” added Soon-Shiong in the press release.1
REFERENCES:
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, Inc. February 27, 2025. Accessed February 27, 2025. https://tinyurl.com/2n2vyrtm
FDA approves nogapendekin alfa inbakicept-pmln for BCG-unresponsive non-muscle invasive bladder cancer. FDA. April 22, 2024. Accessed February 28, 2025. https://tinyurl.com/3bcnrzwy
