ASCO GU 2021: IL-15R alphaFc super-excited agent N-803 studied in patients with NMIBC bladder cancer in place who responded to BCG (QUILT 3.032 trial)

In 2019, the FDA awarded ImmunityBio's IL-15 super agonist N-803 Breakthrough Therapy, which is designed to be used in combination with BCG to treat patients with non-myocardial immersive in-place bladder cancer (CIS) who previously had a poor response to BCG.
ImmunityBio's N-803 is a new IL-15 super-excited compound.
N-803 has improved pharmacodynamic properties and longer durability and enhanced anti-tumor activity in lymphatic tissue compared to natural non-composite IL-15 in the body.
newly diagnosed with bladder cancer have non-muscular immersion disorder (NMIBC).
for moderate or high-risk NMIBC patients and in-place cancer (CIS) patients, BCG-assisted treatment is recommended based on proven benefits for disease recurrence.
although the card-mediated seedling is effective, many patients eventually develop diseases that do not respond to the card-mediated seedling.
years, these patients have had very limited options.
a new treatment option is N-803 (Anktiva), a mutant IL-15-based immunostitulation fusion protein complex (IL-15R alphaFc) that promotes the proliferation and resuscing of natural killer (NK) cells and CD8-T cells instead of regulated T cells.
preliminary data from the IB phase trial in NMIBC patients who were not vaccinated by BCG showed that injections of N-803 and BCG in the bladder induced complete remission and did not relapse during the 24-month follow-up.
, the QUILT 3.032 study was designed to conduct an open label of BCG plus N-803 in the bladder for patients with BCG-free Advanced NMIBC (NCT03022825), and a 3-queue multi-center II/III study.
In the full summary of the 2021 ASCO GU Cancer Symposium: Urological Skin Cancer and Rare Tumors Conference, Dr. Karim Chamie and colleagues reported the interim results of the trial in Queue A, where BCG had no reactive CIS (or no Ta or T1 disease).
in BCG non-reactive CIS patients (with or without Ta or T1 disease), all patients in the queue received in-bladder N-803 plus BCG, which met the standard induction/maintenance treatment options.
for this analysis, the primary endpoint of the queue (A) is the occurrence of CIS Full Mitigation (CR) at any time.
80 patients had joined Queue A by the December 2020 data deadline.
patients in the
group were usually consistent with the BCG resecurable NMIBC queue, with an average age of 73 years, with men in the majority (86%), mostly white (90%), and overall in good health (ECOG PS - 0, 82%).
, the majority of patients had CIS (69%) at the time of the first relapse, while 21% had CIS and Ta and 9% had CIS and T1.
the median from the last BCG dose was 6.2 months, and the median from the first detected recurrence was 2.3 months.
note that the time between the last BCG dose and the first relapse was 2.7 months.
Chamie points out that this is a well-treated cohort study that has been done five times before TURBTs and 16 times before BCG drips (median).
all patients have received BCG.
addition, 78 percent of patients received treatment other than BCG, including 3 percent checkpoint inhibitors, 59 percent chemotherapy, 13 percent interferon and 3 percent vicinium.
Treatment-related AEs are generally low-grade, and patients have good tolerance, including difficulty urinating (18%), 915% blood urine and frequency of urine (14%), urination (8%), bladder spasms (5%), fatigue (8%), chills (6%) and fever (5%).
the occurrence of all other adverse events is 6% or less.
recorded severe adverse events in treatment in 9 subjects, with a 1% chance of any given AE.
noted that none of these were thought to be treatment-related and no severe IE-related AE was found.
addition, there were no treatment-related suspensions or treatment-related level 5 events.
this time (with a medium follow-up time of 10.7 months), 51 (72%) of the 72 assessable patients observed complete remission at any one time, reaching the primary endpoint.
, 10/80 (12.5%) of patients in this BCG non-responsive population have undergone bladder removal.
patients who received CR, CR was maintained for 12 months at 56% and CR for a medium duration of 19.2 months (7.6 months - not achieved).
compared to other drugs in the field of the disease, Dr. Chamie stressed that the data appeared to be good for N-803.
, the authors concluded that treatment had reached its primary endpoint in the QULT 3.032 trial, with a CR rate of 72% and a 56% chance that CR patients would remain CR for at least 12 months.
addition, there are no serious adverse events associated with treatment and the treatment is well-to-do.
represents a new treatment in this rapidly changing field of disease.
addition, Mays Medicine observed that in the trial of pancreatic cancer, the world's first trial of haNK cells (PD-L1.t-haNK) that expressed targeted PD-L1 chimeric antigens (CAR) was used in patients with metastatic pancreatic cancer in a combined way with the IL-15 super-excited compound N-803.
N-803 may have a wide range of anti-tumor therapeutic potential.