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NEW ORLEANS -- Add-On IL15RaFc superagonist N-803 (VesAnktiva) to Bacillus Calmette-Guérin (BCG) treatment led to "a clinically meaningful benefit" in BCG-unresponsive non-muscle invasive bladder cancer (NMIBC), according to results from the QUILT-3-032 study.

Among 83 patients with BCG-unresponsive NMIBC carcinoma in situ (CIS), 59 (71%) achieved a complete response (CR) with the combination (95% CI 60.1%-80.5%), reported Karim Chamie, MD, MSHS, of the University of California Los Angeles, at the American Urological Association annual meeting.

At a median follow-up of 23.9 months, the median duration of response (DoR) was 24.1 months (95% CI 9.9-not reached), and 62% (95% CI 48.0-73.5) of patients achieved a DoR of at least 12 months, while 55% (95% CI 40.1-67.3) had a DoR of least 18 months, and 52% (95% CI 37.0-64.9) achieved a DoR of at least 24 months.

"That's a very high CR," Chamie told Medpage Today. "And there is significant durability of that CR -- more than 70% of patients responded, and half of those patients responded for at least 2 years, or more, which is a significant number."

While the standard of care for patients with high-grade NMIBC is BCG, up to 50% of patients will experience recurrence or progression during or following BCG. Pembrolizumab (Keytruda) and valrubicin (Valstar) are FDA-approved therapies in this setting, but have demonstrated CR rates of <50%, thus bladder preserving therapy for high-grade NMIBC after adequate intravesical BCG therapy remains an unmet need.

The agent was granted FDA fast track status based on phase I data, and breakthrough therapy designation based on interim phase II data, according to developer . The agent also is being .

The ongoing included 160 patients with confirmed NMIBC with either recurrent or persistent CIS (plus or minus papillary disease), within 12 months of receiving adequate BCG. The patients were stratified into two cohorts: 83 patients with CIS (cohort A) and 77 with papillary disease (cohort B).

The authors reported that the cystectomy rate for cohort A was 7% among responders and 15% overall. Bladder cancer-specific progression-free survival was 92% (95% CI 83.4-96.4) at 12 months, 91% (95% CI 81.2-95.4) at 18 months, and 91% (95% CI 81.2-95.4) at 24 months.

As for cohort B, "we don't talk about CR since these patients all must have had endoscopic resection," Chamie said. "So we defined our outcome as disease-free survival [DFS]." In these patients, median DFS was 23.6 months at a median follow-up of 20.7 months, with 12-, 18-, and 24-month DFS rates of 57%, 53%, and 48%, respectively. Of the 77 patients in that group, 73 (95%) avoided radical cystectomy.

Chamie reported that the treatment efficacy of the combination was sustained across all subgroups in both cohorts.

As for safety, "this drug was very well tolerated," Chamie said. The rate of serious treatment-related adverse events (TRAEs) was 1%, but there were no immune-related AEs and only 3% of patients had treatment-related discontinuation. No grade 4 or 5 TRAEs were reported.

The most common grade 1 and 2 TRAEs included dysuria (22%), pollakiuria (19%), hematuria (18%), fatigue (16%), micturition urgency (12%), chills (7%), bladder spasm (6%), pyrexia (5%), urinary tract infection (UTI 5%), noninfective cystitis (4%), nocturia (3%), diarrhea (3%), nausea (2%), positive bacterial test (2%), cystitis (2%), influenza-like illness (2%), and UT pain (2%).

Grade 3 TRAEs occurring in <1% of patients included arthralgia, bacteremia, dysuria, encephalopathy, Escherichia bacteremia, hematuria, myalgia, pain in extremity, pollakiuria, sepsis, UTI, and decreased urine flow.

Patients received 50 mg of intravesical BCG plus 400 µg of N-803 every week for six cycles followed by maintenance therapy for those patients who achieved a CR for up to 2 years, with the option to extend therapy. Those who did not achieve a CR, but experienced a downgrade, had the option of reinduction.

The median age of the patients was 72, most were men (87% in cohort A; 74% in cohort B), and most had an ECOG status of 0 (82%; 77%, respectively). Patients were heavily pretreated, with a mean number of four transurethral resection of the bladder tumor procedures in each cohort, and 16.6 and 12.3 prior BCG doses in the cohorts A and B, respectively.

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