FDA D.I.S.C.O. Burst Edition: FDA approval of Adstiladrin (nadofaragene firadenovec-vncg) for patients with high-risk Bacillus Calmette-Guérin unresponsive non-muscle invasive bladder cancer with carcinoma in situ with or without papillary tumors
Regulatory approval: On December 16, 2022, the FDA approved nadofaragene firadenovec-vncg (Adstiladrin) for adult patients with high-risk Bacillus Calmette-Guérin (BCG)-unresponsive non–muscle invasive bladder cancer with carcinoma in situ (CIS), with or without papillary tumors. Approval was supported by Study CS-003, a multicenter single-arm trial. In the CIS evaluable cohort, complete response (CR) at any time was 51%, median duration of response was 9.7 months, and 46% of responders maintained CR for at least 1 year.
FDA approval (Dec 16, 2022)
The FDA approved nadofaragene firadenovec-vncg (Adstiladrin) for adult patients with high-risk Bacillus Calmette-Guérin (BCG)-unresponsive non–muscle invasive bladder cancer (NMIBC) with carcinoma in situ (CIS), with or without papillary tumors.
Supporting evidence
Efficacy was evaluated in Study CS-003, a multicenter, single-arm trial (N=157) enrolling patients with high-risk NMIBC; 98 patients had BCG-unresponsive CIS evaluable for response.
Patients received 75 mL intravesical instillation (3 × 10^11 viral particles/mL) once every 3 months for up to 12 months, until unacceptable toxicity, or recurrent high-grade NMIBC. Patients without high-grade recurrence could continue dosing every 3 months.
Primary efficacy outcomes: complete response (CR) at any time and duration of response. CR was defined as negative cystoscopy with applicable TURBT/biopsies and urine cytology; random bladder biopsies at five sites were conducted in patients remaining in CR at 12 months.
Results (CIS evaluable cohort): CR rate 51%; median duration of response 9.7 months; 46% of responders remained in CR for ≥1 year.
Safety
Most common adverse events (≥10%; including lab abnormalities >15%): increased glucose, instillation site discharge, increased triglycerides, fatigue, bladder spasm, micturition urgency, increased creatinine, hematuria, decreased phosphate, chills, dysuria, pyrexia.