New Agent Can Improve BCG Response, Quality of Life in Bladder Cancer


The novel drug N-803 boosted response to Bacille Calmette-Guérin therapy in patients with non-muscle invasive bladder cancer, a study showed.

Patients whose non-muscle invasive bladder cancer (NMIBC) carcinoma in situ (CIS) does not respond to the popular therapy Bacille Calmette-Guérin (BCG) may eventually have more luck by adding the novel drug N-803 (ALT-803), according to findings from a group of patients enrolled in the phase 2/3 QUILT-3.032 clinical trial.

The study met its main goal, with a complete response (CR) rate – meaning that there was no detectable amount of disease – of 72%, and a 58.6% probability of maintaining a CR for at least 12 months. Additionally, at an average follow-up of 20.4 months, the median duration of CR was 19.9 months.

“Eighty-five percent of our patients avoided a cystectomy,” said lead study author Dr. Karim Chamie, associate professor of urology at the University of California, Los Angeles. “This intravesical administration is quite favorable, and quite familiar amongst those who normally treat patients with BCG-unresponsive bladder cancer.”

QUILT-3.032 enrolled 81 patients with histologically confirmed BCG-unresponsive NMIBC, with persistent or recurrent CIS within 12 months of receiving adequate BGC treatment. Patients were treated with 50 mg of BCG plus 400 mg of intravesical N-803 weekly for six weeks, followed by re-induction and maintenance for up to three years.

The primary endpoint (main goal) was biopsy-confirmed CR at three and six months. Secondary end points included duration of CR, cystectomy avoidance and time to cystectomy. Furthermore, safety end points included incidence of serious side effects and immune-related side effects.

Notably, the analysis included patients who achieved a CR at 3 months, as well as those who achieved a CR after rescue and re-induction at 6 months.

Those who were enrolled were heavily pretreated patients with an average of five transurethral (performed through the urethra) resections of a bladder tumor, and a median of 12 prior BCG instillations. Additionally, 42% of patients had received prior treatment with chemotherapy, and 17% were previously treated with immunotherapy agents.

Additional data showed that among patients who achieved an initial complete response at three months, there was a 64% probability of maintaining that response at 12 months, and a 61% probability of maintaining it at 18 months.

Notably, as of May 2021, the combination showed a 30% durable response at 18 months. Eighty-five percent of patients have not progressed to radical cystectomy through a data analysis as of this time point, as well.

In terms of safety, the combination was well tolerated, with no incidence of treatment-related serious side effects, immune-related side effects or treatment-related side effects that were grade 4/5 (life-threatening to fatal) in severity. Severe side effects caused by treatment occurred in just two patients and included urinary tract infection and arthralgia. The most frequent grade mild side effects were painful urination (22%), blood in urine (16%) and frequent urination (19%).

In comparison to other FDA-approved treatments for this patient population, N-803 plus BCG significantly improved outcomes. Previous data with Keytruda (pembrolizumab) showed that the agent induced at CR rate of 41% at any time, and a median duration of CR of 16.2 months at 24.1 months follow-up. Similarly, valrubicin elicited an 18% CR rate, and a median duration of CR of less than six months. Moreover, the cystectomy-free rate for the two drugs was 63% and 76%, respectively.

A version of this article was originally published on OncLive as, “N-803/BCG Combo Shows Promising Responses, Tolerability in BCG-Unresponsive Bladder Cancer.”

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