FDA Approval Summary: Nogapendekin Alfa Inbakicept-pmln with BCG for BCG-unresponsive carcinoma in situ.

On April 22, 2024, the U.S. Food and Drug Administration (FDA) granted regular approval to nogapendekin alfa inbakicept-pmln (N-803) with Bacillus Calmette-Guerin (BCG) for the treatment of adult patients with BCG-unresponsive non-muscle invasive bladder cancer (NMIBC) with carcinoma in situ (CIS), with or without papillary tumors. Substantial evidence of effectiveness for this application was obtained from Cohort A of the single-arm, multicenter QUILT-3.032 trial. Patients received N-803 400 μg administered intravesically with TICE BCG once a week for 6 weeks as induction therapy, a second induction course if complete response (CR) was not achieved at month 3, and maintenance N-803 with BCG weekly for 3 weeks at months 4, 7, 10, 13, and 19 (for a total of 15 maintenance doses). The major efficacy outcome measures were CR at any time (as defined by negative results for cystoscopy [with TURBT/biopsies as applicable] per local investigator assessment and urine cytology) and duration of response. The CR rate in the 77-patient efficacy population, per FDA review, was 62% (95% confidence interval [CI]: 51%, 73%). Of the 48 patients with a CR, 28 (58%; 95% CI: 26%, 55%) and 19 (40%; 95% CI: 16%, 36%) maintained a response for ≥12 months and ≥24 months, respectively. The most common adverse reactions were increased creatinine, dysuria, hematuria, urinary frequency, urinary urgency, and urinary tract infection. This article summarizes the data and FDA thought process supporting the approval of N-803 with BCG.