FDA Accepts BLA for Immunotherapy for Bladder Cancer

The FDA has accepted the biologics license application (BLA) for ImmunityBio’s N-803, an IL-15 superagonist in combination with Bacillus Calmette-Guérin (BCG) vaccine. The company is seeking approval for N-803, an antibody cytokine fusion protein with the brand name of Anktiva, to treat patients with BCG-unresponsive non-muscle-invasive bladder cancer carcinoma in situ. The BCG vaccine is the current standard of care in this cancer.

The Prescription Drug User Fee Act target action date is May 23, 2023. The FDA has granted N-803 breakthrough therapy and fast track designations.

If approved, N-803 plus BCG would be the first immunotherapy combination for this indication in 23 years that can be delivered directly to the bladder to induce natural killer cells and T cells. N-803 has a unique mechanism of action that leads to the proliferation of NK and T cells that are cells of the adaptive and innate immune system. Through this action, N-803 provides a secondary boost to the immunological response generated by BCG for bladder cancer, or by a checkpoint inhibitor for other indications.

Patrick Soon-Shiong, M.D.

“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, ImmunityBio’s founder Patrick Soon-Shiong, M.D., executive chairman and global chief scientific and medical officer, said in a press release.

The BLA is based on positive results from a series of studies, including the ongoing phase 2/3 QUILT 3.032 trial. In this study, 71% of patients who had failed on previous therapies showed a more than 50% increase in both response and median duration compared with the FDA-approved alternatives, the chemotherapy Valstar (valrubicin) developed by Endo Pharmaceuticals and Keytruda (pembrolizumab), Merck’s systemic checkpoint inhibitor therapy.

Results of this trial were released at the 2022 American Society of Clinical Oncology.

This combination of N-803 with BCG is ImmunityBio’s first BLA to reach this stage of FDA acceptance for review. The application had been submitted in May 2022.

N-803 is also being studied in advanced metastatic pancreatic cancer. Results from a phase 2 trial, QUILT 88 showed that N-803 and anti–PD-L1 NK cell therapy more than doubles historical overall survival in patients with third- to sixth-line advanced pancreatic cancer. Median overall survival in third-line subjects was two months, and overall survival for the intent-to-treat population of third-, fourth- and fifth-line was eight months.