On 22 April 2024, the US Food and Drug Administration (FDA) approved nogapendekin alfa inbakicept-pmln (Anktiva, Altor BioScience, LLC) with Bacillus Calmette-Guérin (BCG) for adult patients with BCG-unresponsive non-muscle invasive bladder cancer (NMIBC) with carcinoma in situ (CIS) with or without papillary tumours.
Efficacy was evaluated in QUILT-3.032 (NCT0302285), a single-arm, multicentre study of 77 patients with BCG-unresponsive, high-risk NMIBC with CIS 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.
Tumour 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 (CR) at any time and duration of complete response (DoR). CR was defined by a negative cystoscopy (with TURBT/biopsies as applicable) and urine cytology.
The CR rate was 62% (95% confidence interval 51, 73); 58% of patients with CR had a DoR ≥ 12 months and 40% had a DoR ≥ 24 months.
The most common adverse reactions (≥15%), including laboratory test abnormalities, were increased creatinine, dysuria, haematuria, urinary frequency, micturition urgency, urinary tract infection, increased potassium, musculoskeletal pain, chills, and pyrexia.
The recommended nogapendekin alfa inbakicept-pmln dose is 400 mcg administered intravesically with BCG once a week for 6 weeks as induction therapy. A second induction course may be administered if CR is not achieved 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 an ongoing CR 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 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.
This review used the Assessment Aid, a voluntary submission from the applicant to facilitate the FDA’s assessment.
This application was granted breakthrough designation.
Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA’s MedWatch Reporting System.
For assistance with single-patient INDs for investigational oncology products, healthcare professionals may contact FDA’s Oncology Center of Excellence Project Facilitate.