The US Food and Drug Administration (FDA) has expanded the approved indication for nogapendekinalfainbakicept-pmln plus Bacillus Calmette-Guérin (BCG) to include adults with BCG-unresponsive, high-grade papillary-only nonmuscle-invasive bladder cancer (NMIBC).
The October 14, 2026, decision extends the combination's previous indication for BCG-unresponsive NMIBC with carcinoma in situ (CIS), with or without papillary tumors. The expansion was supported by previously established efficacy in patients with CIS and clinical and nonclinical similarities between the 2 tumor types, rather than a separate efficacy trial in patients with papillary-only disease.
The original approval was supported by Cohort A of QUILT-3.032 (NCT03022825), a single-arm, multicenter trial involving 77 patients with BCG-unresponsive, high-risk NMIBC with CIS, with or without Ta/T1 papillary disease, following transurethral resection.
Patients received intravesical nogapendekin alfa inbakicept-pmln with BCG during induction, followed by maintenance therapy for up to 37 months. The primary efficacy measure was complete response, assessed by cystoscopy, urine cytology, and biopsy.
The complete response rate was 62%. Among responders, 58% maintained a response for at least 12 months and 40% for at least 24 months.
For the expanded indication, the FDA determined that the overlapping characteristics of CIS and high-grade papillary tumors supported extrapolating the earlier efficacy findings. Although the tumors differ in their growth patterns, they frequently coexist, can be difficult to distinguish pathologically, and carry substantial risks of recurrence and progression following BCG treatment failure.
The recommended dose is 400 mcg administered intravesically with BCG weekly for 6 weeks. A second induction course may be administered for residual CIS and/or high-grade Ta tumors at month 3. Maintenance treatment consists of 3 weekly instillations at months 4, 7, 10, 13, and 19, with additional treatment possible administered weekly, for 3 weeks through month 37.
Common adverse reactions and laboratory abnormalities, occurring in at least 15% of patients, included increased creatinine, dysuria, hematuria, urinary frequency and urgency, urinary tract infection, increased potassium, musculoskeletal pain, chills, and pyrexia.
The prescribing information warns that delaying cystectomy may result in metastatic bladder cancer, which the FDA noted can be lethal. The agency advised treatment should be discontinued for persistent disease after a second induction course, recurrence, progression, or unacceptable toxicity.
The FDA is also finalizing guidance addressing the use of efficacy evidence from patients with CIS to support treatments for BCG-unresponsive high-grade papillary-only NMIBC.
Sources
US Food and Drug Administration. FDA approves an expanded indication for nogapendekinalfainbakicept-pmln for BCG-unresponsive non-muscle invasive bladder cancer. October 14, 2026.
US Food and Drug Administration. FDA approves nogapendekinalfainbakicept-pmln for BCG-unresponsive non-muscle invasive bladder cancer. April 22, 2024.
