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Jump to Key Points The FDA has approved nogapendekin alfa inbakicept-pmln (Anktiva, Altor BioScience/ ImmunityBio), in combination with bacillus Calmette-Guérin (BCG), for adults with BCG-unresponsive non-muscle invasive bladder cancer (NMIBC).
The approval expands the drug's prior indication for adults with BCG-unresponsive NMIBC with carcinoma in situ (CIS), with or without papillary tumors, to now include patients with high-grade papillary-only tumors.
It also marks what the FDA called a new approach to evaluating treatments for BCG-unresponsive NMIBC: The agency based its decision on the prior demonstration of efficacy in patients with NMIBC containing CIS, citing evidence that those data can be extrapolated to patients with BCG-unresponsive high-grade papillary disease.
"While high-grade papillary and CIS 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, are associated with high risk for tumor recurrence and progression," the FDA said in announcing the expanded indication.
- FDA expanded Anktiva + BCG for BCG-unresponsive NMIBC.
- New indication includes high-grade papillary-only tumors.
- FDA extrapolated CIS efficacy data to papillary disease.
- QUILT-3.032: 62% complete response; 58% lasted ≥12 months.
- Common AEs: creatinine ↑, dysuria, hematuria; cystectomy delay may ↑ metastatic risk.
Anktiva, an interleukin-15 receptor agonist, won approval in 2024 based on findings from QUILT-3.032, a single-arm trial of 77 patients with BCG-unresponsive, high-risk NMIBC with CIS, with or without Ta/T1 papillary disease, following transurethral resection. Patients received Anktiva induction via intravesical instillation with BCG, followed by maintenance therapy for up to 37 months.
Overall, 62% of patients had a complete response, as determined by cystoscopy, urine cytology, and biopsy. Of those patients, 58% had a duration of response of 12 months or more, and 40% had a duration of response lasting at least 24 months.
The most common adverse reactions (≥ 15%) 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.
The recommended dose is 400 µg administered intravesically with BCG once a week for 6 weeks as induction therapy, with an option for a second induction course if patients don't achieve a complete response at 3 months. For maintenance therapy, the recommended dose is 400 mcg with BCG once a week for 3 weeks at months 4, 7, 10, 13, and 19.
Patients with no evidence of high-grade disease at 25 months and beyond may receive maintenance instillations with BCG once a week for 3 weeks at months 25, 31, and 37. The maximum treatment duration is 37 months.
