On April 22, 2024, the interleukin-15 receptor agonist nogapendekin alfa inbakicept-pmln was approved for use with bacillus Calmette-Guérin (BCG) for adults with BCG-unresponsive non–muscle-invasive bladder cancer with carcinoma in situ with or without papillary tumors.1
Supporting Efficacy Data
Approval was based on findings in the multicenter QUILT-3.032 trial (ClinicalTrials.gov identifier NCT0302285). In this study, 77 patients with BCG-unresponsive, high-risk non–muscle-invasive bladder cancer with carcinoma in situ with or without Ta/T1 papillary disease after transurethral resection received nogapendekin alfa inbakicept induction via intravesical instillation with BCG. This regimen was followed by maintenance therapy for up to 37 months.
OF NOTE
Nogapendekin alfa inbakicept has warnings/precautions for delaying cystectomy, which can lead to the development of metastatic bladder cancer. The agent may also cause fetal harm.
Complete response was observed in 48 patients (62%, 95% confidence interval [CI] = 51%–73%). Among patients with a complete response, 58% had a response duration of at least 12 months, and 40% had a response duration of at least 24 months.
How It Is Used
The recommended dose of nogapendekin alfa inbakicept is 400 µg given intravesically with BCG once a week for 6 weeks as induction therapy. A second induction course may be used if a complete response is not achieved at month 3. For maintenance, the recommended dose is 400 µg with BCG once a week for 3 weeks at months 4, 7, 10, 13, and 19 (total of 15 doses). For patients with an ongoing complete response at month ≥ 25, maintenance instillations with BCG may be given once a week for 3 weeks at months 25, 31, and 37, for a maximum of nine additional doses.
Treatment should be discontinued for disease persistence after second induction, disease recurrence or progression, or unacceptable toxicity. The maximum treatment duration is 37 months.
Safety Profile
Among 88 patients in the safety population of QUILT-3.032, the most common adverse events of any grade were dysuria (32%), hematuria (32%), urinary frequency (27%), micturition urgency (25%), urinary tract infection (24%), musculoskeletal pain (17%), chills (15%), and pyrexia (15%). The most common grade 3 or 4 adverse events included hematuria (3.4%), urinary tract infection (2.3%), and musculoskeletal pain (2.3%). The most common grade 3 or 4 laboratory abnormality was increased potassium (2%); any grade of increased creatinine and increased potassium occurred in 76% and 18% of patients, respectively.
Serious adverse events occurred in 16%, most commonly hematuria (3.4%). Adverse events led to discontinuation of treatment in 7%, most commonly musculoskeletal pain (2.3%). A fatal adverse event (cardiac arrest) was reported in one patient.
Nogapendekin alfa inbakicept has warnings/precautions for delaying cystectomy, which can lead to the development of metastatic bladder cancer. The agent may cause fetal harm; females of reproductive potential must be advised of the potential risk to a fetus and to use effective contraception while receiving nogapendekin alfa inbakicept.
REFERENCE
1. U.S. Food and Drug Administration: FDA approves nogapendekin alfa inbakicept-pmln for BCG-unresponsive non-muscle invasive bladder cancer. April 22, 2024. Available at https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-nogapendekin-alfa-inbakicept-pmln-bcg-unresponsive-non-muscle-invasive-bladder-cancer. Accessed May 1, 2024.
