ImmunityBio’s Bladder Cancer Immunotherapy BLA gets FDA Nod

Bladder Cancer

Culver City, Calif.-based ImmunityBio announced that the U.S. Food and Drug Administration had accepted its Biologics License Application (BLA) for N-803 for a specific form of bladder cancer. It was assigned a target action date of May 23, 2023.

N-803 is an antibody cytokine fusion protein. The BLA is for the use of the drug with Bacillus Calmette-Guerin (BCG) to treat patients with BCG-unresponsive non-muscle-invasive bladder cancer carcinoma (NMIBC) in situ (CIS) with or without Ta or T1 disease. The cytokine interleukin-15 (IL-15) has a significant role in the development, maintenance and function of natural killer (NK) and T cells. N-803, a novel IL-15 superagonist complex, directly stimulates CD8+ T cells and NK cells via binding with beta gamma T-cell receptors while avoiding stimulating T-regs (T regulatory cells).

“This BLA acceptance brings us a very important step closer to being able to offer this promising combination therapeutic to more people living with NMIBC and, ultimately, reduce the incidence of cystectomies,” Dr. Patrick Soon-Shiong, M.D., executive chairman and Global global chief scientific and medical officer at ImmunityBio said. “This is a compelling example of the power of inducing trained innate immune memory to potentially provide long-term, durable effects against serious, life-threatening diseases.”

BCG is a well-established treatment for preventing or delaying tumor recurrence after surgery for high-grade nonmuscle invasive bladder cancer (NMIBC). Still, some patients will experience recurrence or progression with or after treatment with BCG. BCG is inserted into the bladder via a catheter. This triggers the immune system to attack the cancer cells. Merck is the only maker and supplier of BCG to the United States and many other countries.

ImmunityBio’s N-803 has received Breakthrough Therapy and Fast Track designations by the FDA for BCG-unresponsive NMIBC CIS and Fast Track designation for BCG-unresponsive NMIBC papillary and BCG-naïve NMIBC CIS.

The BLA was built on data from the QUILT 3.032 Phase II/III trial of intravesical BCG plus N-803 in patients with BCG-unresponsive high-grade NMIBC. The primary endpoints for Cohort A of the trial were the incidence of complete response (CR) of CIS at any time. The data demonstrated that the drug combination gave patients a better chance to avoid removal of the bladder (radical cystectomy). It also included data from 171 patients from Phase I and II trials in bladder cancer and 84 subjects in the QUIT study.

N-803 is also being evaluated for adults in two NMIBC studies. QUILT 2005 is testing N-803 in combination with BCG for patients with BCG-naïve NMIBC. QUILT 3032 is assessing the combination in patients with BCG-unresponsive NMIBC CIS and Papillary Disease.

At the time of the BLA submission, Soon-Shiong noted, “We believe that the durable responses seen in this study (QUILT 3.032) provide further support for our hypothesis that by orchestrating natural killer cells, T cells and memory T cells, long-term durable remissions can be achieved in patients suffering from cancer. The results from the QUILT series of ongoing trials across multiple tumor types, including pancreatic, lung and other solid tumors, could lead to a paradigm shift in cancer therapy that ImmunityBio is developing. We are hopeful that this combination immunotherapy of BCG acting as a prime and N-803 as the boost to the immune system will not only provide a new path for these patients, but also help us continue to broaden our understanding of how we might apply this novel mechanism of action to other difficult-to-treat diseases.”

ImmunityBio is focused on next-generation immunotherapies and vaccines against cancers and infectious diseases. Its pipeline includes 27 clinical trials, 18 in Phase II or III, across 13 indications in liquid and solid tumors and infectious diseases such as COVID-19 and HIV.

Richard Adcock, president and chief executive officer of ImmunityBio, said, “We are pleased the FDA has begun its review, and ImmunityBio is prepared to move rapidly to manufacturing and marketing should the Agency approve our therapeutic for this indication.”

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