N-803-BCG combination shows promising results in BCG-unresponsive NMIBC

Published: 4 Jun 2022

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Dr Karim Chamie - UCLA School of Medicine, Los Angeles, USA

Dr Karim Chamie explores his study in N-803 can result in significant accrual of CD8+ T cells and natural killer cells, without upregulation of regulatory T cells.

Previously, a small phase I trial of N-803 plus BCG in BCG-naive, high-risk non-muscle-invasive bladder cancer (NMIBC) was successful, with complete responses or no disease recurrence seen in all nine included patients; the full cohort was disease-free at 24 months.

He concludes by explaining his findings; of 72 evaluable patients, 51 achieved a complete response (CR) at any time over a median follow-up period of 10.7 months, for a CR rate of 71%, meeting the study’s primary endpoint.

Patients with BCG-unresponsive bladder cancer face significant challenges; there are very limited
treatment options. There are two FDA approved drugs in this indication, one that was not highly
effective and is historical and is no longer being used in real world settings and the other is a drug that
just got FDA approval about two years ago, pembrolizumab. That’s systemic immunotherapy for
patients with BCG-unresponsive bladder cancer and 40% of those patients responded and if you
follow those patients out for a year about half of those that responded fall off.

So if patients who have BCG-unresponsive bladder cancer are either not good candidates for
systemic immunotherapy or are not entirely excited by the low complete response and durability,
they’re looking for other options. Obviously the most effective management of patients with BCG-
unresponsive bladder cancer is a radical cystectomy which means surgical removal of the entire
bladder and surrounding organs and urinary diversion.

When patients are faced with those two options they have to make a choice – is it one that’s
oncologic mediated or the other one that’s quality of life? So the purpose of the QUILT-3.032 study
was to offer both. This is a phase II/III clinical trial for patients with BCG-unresponsive bladder cancer
whereby patients get an IL-15 superagonist, which is N-803, and it’s combined with BCG. The
combination of both those drugs seems to upregulate CD8 and NK cells without upregulation of
regulatory T-cells.

The data seems to be extremely exciting and I think it’s a game changer in how we treat patients with
non-muscle invasive bladder cancer, those that are BCG unresponsive. Our complete response rate
was 71% and if you follow those patients who had a complete response the median durability for
patients with carcinoma in situ plus/minus papillary disease was 26.2 months. The drug was very
effective and very safe – no patients actually had to discontinue due to treatment related toxicities.
Discontinuation rates were pretty low.

What is next in the study?

Obviously N-803 plus BCG is currently in the hands of the FDA but I think there are potential
opportunities in combining this in other disease settings. So is there an opportunity for using this drug
for patients with muscle invasive who seek bladder-sparing options? Is this something that can be
combined with radiation? These are all things that will be truly exciting and moving the field in the
direction of bladder preservation.

Do you have a take-home message for doctors?

N-803 plus BCG is very effective, very safe, well tolerated and hopefully will be available for patients
in the next year.