- QUILT 3.032 study completes planned enrollment of BCG unresponsive non-muscle invasive bladder cancer CIS cohort with a 59% probability of patients maintaining complete response for at least 12 months
- Over 85% of patients in this study have avoided a cystectomy to date
- Breakthrough status for ImmunityBio’s superagonist Anktiva N-803 in this indication
- Biologics License Application filing anticipated in the second half of 2021
With the observed efficacy and only 1% of patients reporting treatment emergent serious adverse events, but none of which were treatment-related, the data support the potential for Anktiva plus BCG as a novel option for BCG unresponsive CIS, a therapeutically challenging disease. Patients with BCG unresponsive CIS disease face surgical removal of the bladder, a procedure fraught with high morbidity and mortality.
Bladder cancer has a high incidence worldwide; it caused 212,536 deaths and an estimated 573,278 new cases were diagnosed in 2020.1 In the United States, bladder cancer is the fourth most commonly diagnosed solid malignancy in men and the twelfth for women; The American Cancer Society estimates 80,470 new cases and 17,670 deaths in 2019.2 Approximately 75-85% of all newly diagnosed cases of bladder cancer are non-muscle invasive bladder cancer (NMIBC).3
The open-label, three cohort multicenter Phase 2/3 study of intravesical BCG plus Anktiva (N-803) in patients with BCG-unresponsive high-grade NMIBC (NCT03022825) was opened in 2017. The primary endpoint for Cohort A of this Phase 2/3 study is incidence of complete response (CR) of CIS at any time. The FDA had granted Fast Track Designation to the pivotal trial based on Phase I data. In December 2019, the FDA granted ImmunityBio Breakthrough Therapy Designation based on interim Phase 2 data indicating the primary endpoint of the trial was already met.
ImmunityBio’s IL-15 superagonist Anktiva (N-803)
“The high rates of progression and recurrence for NMIBC make it one of the most expensive cancers to treat. This preliminary data is heartening and provides additional evidence of the potential for ImmunityBio’s Anktiva in treating a serious and potentially fatal cancer, for which the alternative is a highly invasive radical cystectomy,” said Patrick Soon-Shiong, M.D., Chairman and CEO of ImmunityBio. “We expect to file a Biologics License Application following a meeting with the FDA in 2021.”
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. N-803 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. 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 is currently being evaluated for adult patients in two clinical NMIBC trials. QUILT 2.005 is investigating the use of N-803 in combination with BCG for patients with BCG-naïve NMIBC; QUILT 3.032 is studying N-803 in combination with BCG in patients with BCG-unresponsive NMIBC.
The Urgent, Unmet Need to Treat NMIBC and Avoid Cystectomy
For the last 30 years, BCG immunotherapy has been the standard for treating NMIBC. However, disease recurrence and progression rates remain unacceptably high. Standard of care recommendations for these patients includes lifetime invasive surveillance and rapid treatment of recurrences, creating a substantial financial burden and drastic impact on quality of life. Of those patients who experience recurrence, approximately 30% will progress and succumb to their disease over a 15-year period, and another 50% will undergo radical cystectomy of the bladder in an attempt to control their disease.4
For high-risk NMIBC patients who are BCG-unresponsive with persistent or recurrent disease, treatment guidelines recommend a surgical procedure called a radical cystectomy, a surgery to remove the entire bladder that may require removal of other surrounding organs. In men, removal of the prostate may be necessary, and in women, surgeons may also remove the uterus, fallopian tubes, ovaries and cervix, and occasionally a portion of the vagina. Despite the advent of minimally invasive procedures and robotic techniques, the 90-day mortality and morbidity rates in patients who undergo cystectomy remain unacceptably high at 5.1-8.1% and 28-64%, respectively.5 Based on this urgent need, FDA published guidance in February 2018 to address BCG unresponsive non-muscle invasive bladder cancer (NMIBC), stating that the goal of therapy in patients with BCG-unresponsive NMIBC is to avoid cystectomy.
References:
- Global cancer statistics: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries: https://gco.iarc.fr/
- https://www.cancer.org/cancer/bladder-cancer/about/key-statistics.html
- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3263923/
- https://doi.org/10.1016/j.eururo.2018.09.028
- https://doi.org/10.1016/j.eururo.2013.12.018