An Urgent Need to Treat Bladder Cancer and Prevent Radical Cystectomy

Non-muscle invasive bladder cancer (NMIBC) is the most common form of bladder cancer. It accounts for between 75%-85% of all diagnoses. The standard treatment for NMIBC for three decades has been Bacillus Calmette–Guérin (BCG)1.

While BCG is an effective treatment for many patients, it doesn’t work for an estimated 40% of NMIBC cases2. That can mean a lifetime of invasive examinations followed by immediate treatment for a recurrence. It diminishes quality of life and poses a significant financial burden for most patients – and 30% of patients with a recurrence will decline and succumb over the course of 15-years. For another 50% of patients, controlling the disease will require them to undergo radical cystectomy of the bladder, surgery that removes the entire bladder and, often, other surrounding organs3.

The FDA has issued guidance for the design of studies for the development of NMIBC treatments that includes the goal of avoiding this drastic surgery.

About Our QUILT 3.032 Bladder Cancer Study and FDA Breakthrough Designation

AnktivaImmunityBio has been investigating a novel therapeutic approach to NMIBC that combines Anktiva (N-803) with intravesical BCG in patients with BCG-unresponsive high-grade NMIBC (NCT03022825). Opened in 2017, the QUILT 3.032 trial is an open-label, three cohort, multicenter Phase 2/3 study of this combination. The primary endpoint for Cohorts A and C is incidence of complete response (CR) of CIS at any time. The primary endpoint for Cohort B (papillary disease) is the 12-month disease free rate.

The FDA granted Fast Track Designation to this pivotal trial, based on positive data from an earlier Phase I trial. 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. These special designations allow ImmunityBio to accelerate the bladder cancer clinical trial process toward potential approval and availability for patients.

Positive Data on Sustained Complete Response in 72% of Patients

In September 2021, the trial’s principal investigator Dr. Karim Chamie at UCLA reported positive results in 58 of the 81 patients (72%) in one cohort to treatment with a combination of intravesical BCG plus N-803 (Anktiva). These patients, in Cohort A of the QUILT 3.032 study, had a complete response (CR) at any time (three or six months); the median duration of the complete response was 19.9 months. In addition, 85% of the patients in the cohort avoided a cystectomy, with a median duration of follow-up of 20.4 months. Investigators reported that the investigative bladder cancer immunotherapy was extremely well tolerated with no treatment-related serious adverse events and no immune-related adverse events. This compares to an incidence of 21% immune-related adverse events with the currently approved checkpoint therapy for this indication.

About ImmunityBio’s IL-15 Receptor Agonist Anktiva (N-803)

Cytokines are small proteins in the body that play a variety of roles as “messengers” in the immune system. One of them, interleukin-15 (IL-15), affects the development, maintenance, and function of the immune system’s natural killer (NK) and T cells, key defense mechanisms against infections and tumors. N-803 is a novel IL-15 superagonist complex – that is, a version of a natural activator of cellular receptors (agonist) but that produces a much greater response. N-803 consists 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. Because of these attributes, it has the potential to be an effective part of therapies being developed to target a wide range of cancers, and is currently being studied in more than 24 clinical trials across 18 indications.

Karim Chamie
M.D., Associate Professor of Urology, David Geffen School of Medicine at UCLA.
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.

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