On October 14, 2026, the U.S. Food and Drug Administration (FDA) approved the IL-15 receptor agonist nogapendekin alfa inbakicept-pmln (Anktiva) in combination with bacillus Calmette-Guérin (BCG) for the treatment of adults with BCG-unresponsive non–muscle-invasive bladder cancer (NMIBC).
This revises the prior indication for adults with BCG-unresponsive NMIBC with carcinoma in situ with or without papillary tumors to include patients with high-grade papillary-only tumors.
QUILT-3.032
Efficacy for the combination regimen was previously demonstrated in Cohort A of the single-arm, multicenter, phase II/III QUILT-3.032 trial (ClinicalTrials.gov identifier NCT03022825), which included 77 patients with BCG-unresponsive, high-risk NMIBC with carcinoma in situ with or without Ta/T1 papillary disease following transurethral resection.
Patients received nogapendekin alfa inbakicept-pmln induction via intravesical instillation with BCG followed by maintenance therapy for up to 37 months. The main efficacy outcome measure was complete response, as determined by cystoscopy, urine cytology, and biopsy. Duration of response was an additional efficacy outcome measure. The complete response rate was 62% (95% confidence interval [CI] = 51%–73%). Fifty-eight percent of patients with a complete response had a duration of response of at least 12 months, and 40% had a duration of response of at least 24 months.
The current approval expands the indication to include patients with BCG-unresponsive high-grade NMIBC with papillary-only tumors based on review of available scientific information.
Although high-grade papillary and carcinoma in situ tumors have different architectural growth features, both are considered aggressive urothelial carcinomas, frequently coexist, can be difficult to distinguish pathologically, and, in the BCG-unresponsive setting, they are associated with high risk for tumor recurrence and progression.
Based on the overlapping clinical and nonclinical features of these two histologic types, the FDA concluded that the prior demonstration of efficacy in patients with BCG-unresponsive NMIBC containing carcinoma in situ could be extrapolated to patients with BCG-unresponsive high-grade papillary disease.
Therefore, the indication for nogapendekin alfa inbakicept-pmln with BCG was expanded to include patients with BCG-unresponsive NMIBC with papillary-only tumors. The FDA is working toward finalizing the Guidance for Industry, 'Bacillus Calmette-Guérin–Unresponsive Nonmuscle Invasive Bladder Cancer: Developing Drugs and Biological Products for Treatment' to address this approach.
The most common adverse reactions (≥ 15%), including laboratory test abnormalities, were increased creatinine, dysuria, hematuria, urinary frequency, micturition urgency, urinary tract infection, increased potassium, musculoskeletal pain, chills, and pyrexia.
The prescribing information includes a warning that delaying cystectomy can lead to the development of metastatic bladder cancer, which can be lethal.
Recommended Dosage
The recommended dose for nogapendekin alfa inbakicept-pmln is 400 mcg administered intravesically with BCG once a week for 6 weeks as induction therapy. A second induction course may be administered if patients have residual carcinoma in situ and/or high-grade Ta tumors at month 3. For maintenance after induction therapy, the recommended dose is 400 mcg administered intravesically with BCG once a week for 3 weeks at months 4, 7, 10, 13, and 19 (for a total of 15 doses).
For patients with no evidence of high-grade disease at month 25 and later, maintenance instillations with BCG may be administered once a week for 3 weeks at months 25, 31, and 37 for a maximum of 9 additional instillations. Treatment should be discontinued for disease persistence after second induction, disease recurrence or progression, or unacceptable toxicity. The maximum treatment duration is 37 months.
