ImmunityBio Announces Positive Durable Responses in BCG Unresponsive Bladder Cancer Patients with a Complete Response Rate of 72%, Median Duration of Complete Response of 19.9 Months, and 85% Remaining Cystectomy-free in Phase 2/3 Trial
- 58 out of 81 (72%) patients achieved a complete response at any time (three or six months), which compares favorably to historical complete response rates of 41% and 18% for FDA-approved therapies pembrolizumab and valrubicin, respectively
Median duration of complete response in all responders is 19.9 months and 85% of patients enrolled in the study have avoided a cystectomy as of
- 61% probability of initial responders (complete response at three months) remaining disease free at 18 months
- 0% treatment- or immune-related adverse events (AEs) or serious adverse events (SAEs) reported
The data also showed a 59% probability (95% confidence interval; 43.1%, 71.2%) that responding patients would maintain a complete response for more than 12 months, based on Kaplan-Meier analysis. For the patients who had a CR within the first three months, the CR rate was 77%, with a 61% probability of remaining disease free at 18 months with the median duration of complete response having not yet been reached in that group. 85% of patients in the cohort avoided a cystectomy with a median duration of follow-up of 20.4 months.
Of note, the therapy was extremely well tolerated with 0% treatment-related SAEs, 0% immune-related AEs and 0% grade 4 or 5 treatment-related AEs. In contrast, the currently approved checkpoint therapy for this indication is associated with an incidence of 21% immune-related adverse events.
“The data suggest that a high percentage of patients who respond within the first three months to treatment will maintain that complete response for 18 months and possibly beyond. But most importantly, 85% of the patients in the cohort avoided a cystectomy,” said Principal Investigator
The data was announced on
Bladder cancer has a high incidence worldwide; in 2020, an estimated 573,278 new cases were diagnosed and it was the cause of 212,536 deaths1. In
“We are pleased with the sustained durable response and the significant avoidance of cystectomy in this patient population. In those patients who responded by three months after the initial treatment, it is encouraging to see that the median duration of that response, even after 18 months, has not yet been reached,” said
Soon-Shiong continued, “We are encouraged by these results showing the potential for a higher and longer-lasting rate of complete response than with the current standards of care in patients facing removal of the bladder as an alternative. This study provides insights into the power of harnessing the immune system, including NK cells and T cells, which are activated by N-803. What is more, the novel IL15 fusion protein N-803 being studied was designed to be administered safely in the urologist’s office, potentially enabling ease of administration and increasing access for patients.”
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 include 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— a surgery to remove the entire bladder that may require removal of other surrounding organs—in an attempt to control their disease4.
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 3-6% and 28-64%, respectively5 & 6. Based on this urgent need, FDA published guidance in
About the Study and Breakthrough Designation
QUILT 3.032 is an 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) and 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
ImmunityBio’s IL-15 superagonist Anktiva (N-803)
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. 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. 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 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 company’s platforms are based on the foundation of four separate modalities: Antibody cytokine fusion proteins, synthetic immunomodulators, second-generation human adenovirus (hAd5) and yeast vaccine technologies, and state-of-the-art, off-the-shelf natural killer cells, including autologous and allogenic cytokine-enhanced memory NK cells.
Forward Looking Statements
This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, such as statements regarding the development of therapeutics for cancer and infectious diseases, the advancement of our Phase II and III trials, and regulatory approval, commercialization and commercial success of ImmunityBio’s product candidates and related matters. Statements in this press release that are not statements of historical fact are considered forward-looking statements, which are usually identified by the use of words such as “anticipates,” “believes,” “continues”, “could”, “estimates,” “expects,” “intends,” “may,” “plans,” “potential”, “predicts”, “projects,” “seeks,” “should,” “will,” and variations of such words or similar expressions. Statements of past performance, efforts, or results of our clinical trials, about which inferences or assumptions may be made, can also be forward-looking statements and are not indicative of future performance or results. Forward-looking statements are neither forecasts, promises nor guarantees, and are based on the current beliefs of ImmunityBio’s management as well as assumptions made by and information currently available to
- Global cancer statistics: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries: https://gco.iarc.fr/
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