Dr Chamie on the FDA Approval of N-803 Plus BCG for BCG-Unresponsive NMIBC

Karim Chamie, MD, associate professor, urology, the University of California, Los Angeles, discusses the significance of the FDA approval of nogapendekin alfa inbakicept-pmln (Anktiva; N-803) plus Bacillus Calmette–Guérin (BCG) for patients with BCG-unresponsive non–muscle invasive bladder cancer (NMIBC).

 for the treatment of patients with BCG-unresponsive NMIBC with carcinoma in situ (CIS) with or without papillary tumors. This regulatory decision was based on findings from the phase 2/3 QUILT-3.032 trial (NCT03022825), in which a complete response (CR) rate of 62% (95% CI, 51%-73%) was observed in patients with BCG-unresponsive NMIBC who received the combination (n = 77). Notably, 58% of patients who achieved a CR experienced a duration of response (DOR) lasting at least 12 months, and 40% of patients with a CR experienced a DOR lasting 24 months or longer. Previously reported findings from cohort A of QUILT-3.032, which included patients with CIS, showed that the combination induced a CR rate of 71% (95% CI, 59.6%-80.3%) among 82 patients who had experienced disease progression on prior treatment. The median follow-up for this analysis was 23.9 months.

Commonly reported adverse effects in QUILT-3.032 included dysuria, increased creatinine, hematuria, micturition urgency, urinary frequency, urinary tract infection, musculoskeletal pain, increased potassium, pyrexia, and chills.

This FDA-approved regimen is a welcome addition to the NMIBC treatment paradigm, Chamie says. Although patients with bladder cancer face a challenging diagnosis, the current array of therapies for this disease provides patients with several effective treatment options, Chamie emphasizes. Historically, BCG-unresponsive NMIBC has been considered an end-stage disease, and patients with this disease have often needed to undergo a cystectomy, Chamie explains. However, the combination of N-803 and BCG provides these patients with an alternative to bladder removal, according to Chamie.

With this approval, N-803 joins an array of other FDA-approved treatment options for patients with NMIBC but will likely be considered the best-in-class agent, Chamie notes. Now that this agent is commercially available, many patients with BCG-unresponsive disease will seek access to this therapy, Chamie concludes.

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Karim Chamie, MD, discusses the FDA approval of nogapendekin alfa plus BCG for patients with BCG-unresponsive non–muscle invasive bladder cancer.

Karim Chamie, MD, associate professor, Urology, UCLA Health, discusses the design of the phase 2/3 QUILT-3.032 trial (NCT0302282) in patients with Bacillus Calmette-Guerín (BCG)–unresponsive, non–muscle invasive bladder cancer carcinoma in situ.

BCG-unresponsive bladder cancer is not a disease that is common, and because of this, the FDA approves drugs that have achieved certain milestones, according to Chamie. For example, phase 3 trials where patients are randomized to placebo or the study drug are not necessary in the patient population. Instead, the FDA has allowed companies to develop single-arm studies in which every patient receives the investigational agent, Chamie adds.

As such, in the single-arm QUILT-3.032 study, every patient received N-803 plus BCG, Chamie concludes. At the 2021 AUA Annual Meeting, data from the interim analysis of cohort A of the trial, which was comprised of patients with BCG-unresponsive NMIBC carcinoma in situ (CIS). The primary end point of this cohort was incidence of complete response of CIS at any time, and it was met.

Karim Chamie, MD, discusses the design of the phase 2/3 QUILT-3.032 trial in patients with Bacillus Calmette-Guerín–unresponsive, non–muscle invasive bladder cancer carcinoma in situ.

Karim Chamie, MD

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