Vaccine Info

N-803 plus BCG Vaccine Therapy

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Last reviewed
January 12, 2023

N-803 plus BCG Vaccine Therapy Description

ImmunityBio's IL-15 Superagonist N-803 Plus BCG is a therapy to treat adults with Non—muscle-invasive Bladder Cancer (NMIBC) carcinoma in situ (CIS) with or without Ta/T1 papillary disease. N-803 (generic name nogapendekin alfa inbakicept or NAI) is a novel IL-15 superagonist complex consisting of an IL-15 mutant (IL-15N72D) bound to an IL-15 receptor α/IgG1 Fc fusion protein. Its mechanism of action is direct specific stimulation of CD8+ T cells and NK cells through beta gamma T-cell receptor binding (not alpha) while avoiding T-reg stimulation.

The cytokine interleukin-15 (IL-15) plays a crucial role in the immune system by affecting the development, maintenance, and function of the natural killer (NK) and T cells. The IL-15 superagonist N-803 acts synergistically with Bacille Calmette-Guerin (BCG). N-803 has improved pharmacokinetic properties, longer persistence in lymphoid tissues, and enhanced anti-tumor activity compared to native, non-complexed IL-15 in vivo.

N-803 has been studied in more than 700 patients in multiple phase 1 and 2 clinical trials in liquid and solid tumors. In addition to the study in NMIBC, it is currently being studied in trials for pancreatic cancer, non-small-cell lung cancer, non-Hodgkin's lymphoma, and HIV. On November 10, 2022, the peer-review journal NEJM Evidence published its conclusion from a phase 2/3 study: In patients with BCG-unresponsive bladder carcinoma in situ and papillary NMIBC treated with BCG and the novel agent NAI, CRs were achieved with the persistence of effect, cystectomy avoidance, and 100% bladder cancer–specific survival at 24 months.

"The peer review and publication of data in NEJM Evidence highlight the significance of the positive results of the QUILT 3.032 trial in patients with BCG-unresponsive NMIBC," said Patrick Soon-Shiong, M.D., Executive Chairman and Global Chief Scientific and Medical Officer at ImmunityBio, in a press release on November 10, 2022. "These data further our understanding of N-803's unique role in potentially boosting the proliferation of natural killer and T cells while synergistically enhancing BCG efficacy."

On December 27, 2022, an editorial from urological cancer experts from Memorial Sloan Kettering Cancer Center stated: "The efficacy and minimal toxicity of this combination represents a major advance for the care of patients with BCG-unresponsive NMIBC, and the authors should be congratulated. In addition, this promising combination offers a potential alternative to cystectomy and may allow us to move beyond single-arm studies toward randomized phase 3 trials against other novel therapies."

The TICE® BCG vaccine from Merck is used in this therapy.

Based in Culver City, CA, ImmunityBio is a vertically integrated, clinical-stage biotechnology company developing next-generation therapies and vaccines that bolster the natural immune system to defeat cancers and infectious diseases. ImmunityBio's clinical pipeline consists of 27 clinical trials—18 of which are in phase 2 or 3 development.

U.S. FDA Review N-803 Plus BCG Therapy

The Food and Drug Administration (FDA) is reviewing (July 2022) the Biologics License Application (BLA) for N-803 plus BCG for the treatment of NMIBC CIS with a Prescription Drug User Fee Act (PDUFA) date of May 23, 2023.

N-803 plus BCG Therapy Indication

The company stated while BCG is an effective treatment for many patients, it doesn't work for an estimated 40% of NMIBC cases. Patients with intermediate or high-risk NMIBC typically receive a treatment of transurethral resection of the bladder tumor (TURBT) followed by BCG intravesical instillation. However, cancer will recur in 30% to 40% of patients with NMIBC despite adequate treatment with BCG. Moreover, even among those in whom a complete response is achieved with BCG, up to 50% see their cancer return.

N-803 plus BCG Therapy News

November 10, 2022 -  NEJM Evidence has published results from the QUILT 3.032 phase 2/3 clinical trial studying N-803 plus BCG in adults with NMIBC CIS with or without Ta/T1 papillary disease.

July 28, 2022 - The U.S. FDA accepted a BLA from ImmunityBio, Inc for review.

May 23, 2022 - ImmunityBio, Inc. announced it had submitted a BLA to the U.S. FDA for N-803.

February 2022 - Data presented at the ASCO® Genitourinary Cancers Symposium showed a complete response in 59 of 83 patients 71% CR rate (95% CI: 60.1, 80.5) and a median duration of CR of 24.1 months. In patients who responded to the investigational therapeutic, the probability of avoiding both bladder cancer and cystectomy progress at 24 months exceeded 90%. In addition, the combination of Anktiva and BCG had a well-tolerated profile with 0% treatment-related serious adverse events (SAEs), 0% immune-related AEs, and 100% bladder cancer-specific overall survival at 24 months.

January 2019 - ScienceDirect published a Brief Correspondence: Prognostic Implication of the U.S. FDA-defined BCG-unresponsive Disease.

N-803 plus BCG Clinical Trials

QUILT 3.032 Registrational Trial of IL-15 Superagonist N-803 Plus BCG in Patients with Bladder Cancer - results presentation.