FDA Approves IL-15 Receptor Agonist for BCG-Unresponsive NMIBC

FDA Approves IL-15 Receptor Agonist for BCG-Unresponsive NMIBC

The FDA has approved nogapendekin alfa inbakicept-pmln (Anktiva) plus Bacillus Calmette-Guérin (BCG) for the treatment of adult patients with BCG-unresponsive non-muscle invasive bladder cancer (NMIBC) with carcinoma in situ, with or without papillary tumors.¹

This FDA approval was based on findings from the QUILT-3.032 trial (NCT0302285). In this single-arm, multicenter trial, researchers assessed data from 77 patients with BCG-unresponsive, high-risk NMIBC with carcinoma in situ with or without Ta/T1 papillary disease after transurethral resection, according to the FDA’s release. Patients in this trial were treated with nogapendekin alfa inbakicept-pmln induction administered by intravesical instillation with BCG followed by maintenance therapy for up to 37 months.

Researchers assessed tumor status by cystoscopy and urine cytology every 3 months for up to 2 years. In addition, either random or cystoscopy-directed biopsy was required within the first 6 months after treatment was initiated. Local community standards were used to assess patients subsequently.

One of the major efficacy outcomes of the QUILT-3.032 trail was complete response (CR) at any time, defined as a negative cystoscopy with TURBT/biopsies, as applicable, and urine cytology. Duration of response (DOR) was another major efficacy outcome.

The rate of CR in this trial was 62% (95% CI, 51%-73%). Of note, 58% of patients with a CR had a DOR of at least 12 months, and 40% of patients had a DOR of at least 24 months.

The most common adverse reactions, occurring in at least 15% of patients, included dysuria, increased creatinine levels, hematuria, micturition urgency, urinary frequency, increased potassium levels, urinary tract infection, chills, musculoskeletal pain, and pyrexia.

According to the FDA’s release, the recommended dose of nogapendekin alfa inbakicept-pmln is 400 mcg given intravesically with BCG once a week for 6 weeks as induction therapy. If CR is not achieved at month 3, a second induction course may be administered. Maintenance after induction therapy can include a 400 mcg dose of nogapendekin alfa inbakicept-pmln administered intravesically with BCG once per week for 3 weeks at months 4, 7, 10, 13, and 19, for a total of 15 doses.

For patients who experience ongoing CR after 25 months, maintenance instillations with BCG may be given once per week for 3 weeks at months 25, 31, and 37 for a maximum of 9 additional instillations. Treatment discontinuation should occur if disease persists after the second induction, unacceptable toxicity, or disease recurrence or progression, according to the FDA. The maximum treatment duration with nogapendekin alfa inbakicept-pmln is 37 months.

Nogapendekin alfa inbakicept-pmln is an interleukin-15 receptor agonist that is indicated with BCG, according to the drug’s prescribing information.² It comes in a 400 mcg/0.4 mL dose as a clear to slightly opalescent and slightly yellow solution in single-dose vials. Although there are no contraindications, there is a warning that notes that delaying cystectomy can lead to metastatic bladder cancer.

References

1. FDA approves nogapendekin alfa inbakicept-pmln for BCG-unresponsive non-muscle invasive bladder cancer. News release. FDA. April 22, 2024. Accessed April 22, 2024. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-nogapendekin-alfa-inbakicept-pmln-bcg-unresponsive-non-muscle-invasive-bladder-cancer
2. Nogapendekin alfa inbakicept-pmln. Altor BioScience, LLC. April 2024. Accessed April 22, 2024. https://www.accessdata.fda.gov/drugsatfda_docs/label/2024/761336s000lbl.pdf