On April 22, the U.S. Food and Drug Administration (FDA) approved nogapendekin alfa inbakicept-pmln (Anktiva) with bacillus Calmette-Guérin (BCG) for adults with BCG-unresponsive non–muscle invasive bladder cancer with carcinoma in situ with or without papillary tumors.
QUILT-3.032 Trial
Efficacy was evaluated in QUILT-3.032 (ClinicalTrials.gov identifier NCT0302285), a single-arm, multicenter trial in 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. Patients received nogapendekin alfa inbakicept-pmln induction via intravesical instillation with BCG followed by maintenance therapy for up to 37 months.
Tumor status was assessed with cystoscopy and urine cytology every 3 months for up to 2 years, and biopsy (random or cystoscopy-directed) was required within the first 6 months after treatment initiation. Subsequent assessment was performed per local community standards.
The major efficacy outcome measures were complete response at any time and duration of complete response. Complete response was defined by a negative cystoscopy (with transurethral resection/biopsies as applicable) and urine cytology.
The complete response rate was 62% (95% confidence interval = 51%–73%). Overall, 58% of patients with a complete response had a response duration of at least 12 months, and 40% had a response duration of at least 24 months.
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.
Dosage Recommendations
The recommended nogapendekin alfa inbakicept-pmln dose is 400 μg administered intravesically with BCG once a week for 6 weeks as induction therapy. A second induction course may be administered if a complete response is not achieved within 3 months. For maintenance after induction therapy, the recommended dose is 400 μg 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 an ongoing complete response at month 25 or later, maintenance instillations with BCG may be administered once a week for 3 weeks at months 25, 31, and 37, for a maximum of nine 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.
Expedited Programs
This review used the Assessment Aid, a voluntary submission from the applicant to facilitate the FDA’s assessment. The application was granted Breakthrough Therapy designation.
