NEW ORLEANS – Add-on therapy of IL15RaFc-supernatural N-803 (VesAnktiva) to Bacillus Calmette-Guérin (BCG) has resulted in a ‘clinically feasible benefit’ in non-muscle-invasive bladder cancer (NMIBC) that does not respond to BCG, according to results from the QUILT-3 study. -032.
Of the 83 patients with unresponsive BCG-NMIBC carcinoma in situ (CIS), 59 (71%) achieved a complete response (CR) with the group (95% CI 60.1%-80.5%), reported Karim Shami, MD. , MSHS, of the University of California, Los Angeles, at the annual meeting of the American Urological Association.
At a median follow-up of 23.9 months, the median DoR was 24.1 months (95% CI 9.9 not reached), 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) achieved a DoR of at least 18 months, and 52% (95% CI 37.0-64.9) achieved a DoR of at least 24 months.
“That’s a very high heart rate,” Shami said. Medpage today. “And there’s a huge robustness to that CR — more than 70 percent of patients responded, half of those patients responded for at least two years, or longer, 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 after BCG. Pembrolizumab (Keytruda) and valrubicin (Valstar) are FDA-approved treatments in this setting, but have shown CR rates of less than 50%, and thus bladder-preserving therapy for high-grade NMIBC after appropriate treatment of intravesical BCG remains an unquestioned need. satisfied.
The agent has been granted fast-track status by the U.S. Food and Drug Administration based on Phase 1 data, and assigned advanced treatment based on provisional Phase 2 data, according to developer ImmunityBio. The agent is also being tested in breast cancer.
The ongoing QUILT-3-032 study included 160 patients with confirmed NMIBC with either recurrent or persistent CIs (plus or minus papillary disease), within 12 months of receiving appropriate BCG. The patients were divided into two groups: 83 patients with CIS (cohort A) and 77 patients with papillary disease (cohort B).
The authors reported that the cystectomy rate for cohort A was 7% among responders and 15% overall. The progression-free survival rate for bladder cancer 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.
For cohort B, “we’re not talking about CR because all of these patients should have had a laparoscopic resection,” Shami said. “So we defined our result as disease-free survival [DFS]. In these patients, the median DFS was 23.6 months with a median follow-up of 20.7 months, with DFS rates for 12, 18 and 24 months of 57%, 53%, and 48%, respectively. Patients in that group, 73 (95% ) Avoid radical cystectomy.
Shami reported that the treatment efficacy of the combination persisted in all subgroups in both groups.
As for safety, Shami said, “this drug was well tolerated.” The rate of treatment-related serious adverse events (TRAEs) was 1%, but there were no immune-related AEs and only 3% of patients discontinued treatment. No grade 4 or 5 TRAEs were reported.
Grade I and II TREEs included dysuria (22%), pollakiuria (19%), hematuria (18%), fatigue (16%), urgent urination (12%), chills (7%), and bladder spasm (6 )%), fever (5%), urinary tract infection (UTI 5%), non-infectious cystitis (4%), nocturia (3%), diarrhea (3%), nausea (2%), positive bacterial test (2%), cystitis (2%), influenza-like illness (2%), urinary tract infection pain (2%).
Grade 3 TREs occurring in less than 1% of patients include arthralgia, bacteremia, dysuria, encephalopathy, escherichia bacteremia, hematuria, myalgia, pain in extremities, pollakiuria, sepsis, urinary tract infection, and lower urine flow;
Patients received 50 mg of intravesical BCG plus 400 mcg of N-803 every week for six cycles followed by maintenance therapy for those patients who had CR for up to two years, with the option to extend treatment. Those who did not achieve a CR, but had a rating downgrade, have the option to restart.
The mean age of patients was 72 years, most of them were men (87% in group A, 74% in group B), and most had zero ECOG status (82%, 77%, respectively). Patients underwent significant pretreatment, with a mean number of four transurethral resections for bladder tumor procedures in each group, and 16.6 and 12.3 prior BCG doses in cohorts A and B, respectively.
The study was supported by ImmunityBio.
Chamie has reported on its relationships with ImmunityBio, Urogen Pharma, Bristol Myers Squibb and Merck Scientific.