FDA Expands Nogapendekin Alfa Inbakicept Indication in BCG-Unresponsive NMIBC

The FDA has expanded the indication for nogapendekin alfa inbakicept-pmln (Anktiva) in combination with Bacillus Calmette-Guérin (BCG) to include adults with BCG-unresponsive non-muscle invasive bladder cancer (NMIBC) with high-grade papillary-only tumors.¹

Nogapendekin alfa inbakicept was originally approved by the FDA in April 2024 for patients with BCG-unresponsive NMIBC with carcinoma in situ (CIS), with or without papillary tumors. The expanded indication broadens the agent's use to patients with high-grade papillary-only disease, a population with limited bladder-sparing treatment options.

The approval follows the evaluation of available information from the phase 2/3 QUILT-3.032 trial (NCT03022825), which supported original approval. Previously reported findings from the trial demonstrated durable disease control and high rates of cystectomy avoidance among patients with BCG-unresponsive papillary-only NMIBC.

Efficacy Data From QUILT-3.032

The original indication was supported by findings from cohort A of the QUILT-3.032 trial, a single-arm, multicenter study involving 77 patients with BCG-unresponsive, high-risk NMIBC with CIS, with or without Ta/T1 papillary disease, following transurethral resection.² Patients received intravesical nogapendekin alfa inbakicept in combination with BCG during induction, followed by maintenance treatment for up to 37 months.

The primary efficacy measure was complete response (CR), assessed through cystoscopy, urine cytology, and biopsy. Duration of response (DoR) was an additional efficacy outcome.

Cohort B of QUILT-3.032 evaluated patients with BCG-unresponsive, high-grade papillary-only NMIBC. In a 36-month analysis, the combination was associated with a disease-specific survival rate of 96.0% (95% CI, 88.2%-98.7%), while median disease-specific survival was not reached.³ Disease-free survival (DFS) rates were 58.2% at 12 months, 52.1% at 24 months, and 38.2% at 36 months.

Progression-free survival (PFS) was 94.9% at 12 months and 83.1% at 36 months. Cystectomy avoidance rates were 92.2% at 12 months and 81.8% at 36 months. The findings address an important treatment consideration in BCG-unresponsive papillary disease, for which radical cystectomy has traditionally been the definitive treatment option.

Safety Profile

Urinary and laboratory abnormalities accounted for several of the most frequently reported adverse reactions, including dysuria, hematuria, urinary frequency and urgency, urinary tract infection, and elevated creatinine and potassium levels.

Other common reactions, each occurring in at least 15% of patients, included musculoskeletal pain, chills, and pyrexia. The FDA also cautions that deferring cystectomy may permit disease progression to metastatic bladder cancer, which can be fatal.

REFERENCES

1. FDA approves an expanded indication for nogapendekin alfa inbakicept-pmln for BCG-unresponsive non-muscle invasive bladder cancer. News release. US FDA. October 14, 2026. Accessed October 14, 2026. https://tinyurl.com/2y44m6tn

2. QUILT-3.032: A Multicenter Clinical Trial of Intravesical Bacillus Calmette-Guerin (BCG) in Combination With ALT-803 (N-803) in Patients With BCG Unresponsive High Grade Non-Muscle Invasive Bladder Cancer. ClinicalTrials.gov. Updated October 16, 2025. Accessed October 14, 2026. https://clinicaltrials.gov/study/NCT03022825

3. Chang SS, Chamie K, Kramolowsky E, et al. Prolonged Progression-Free Survival, Disease-Free Survival, and Cystectomy Avoidance With IL-15 Receptor Lymphocyte-Stimulating Agent NAI Plus Bacillus Calmette-Guérin in Bacillus Calmette-Guérin-Unresponsive Papillary-Only Nonmuscle-Invasive Bladder Cancer. J Urol. 2026;215(1):44-56. doi:10.1097/JU.0000000000004782