FDA Expands Nogapendekin Alfa Inbakicept Plus Bacillus Calmette-Guérin Approval to Include High-Grade Papillary-Only Bladder Cancer

Clinical Summary: 

• Regulatory Update: The FDA has expanded the indication for nogapendekin alfa inbakicept plus Bacillus Calmette-Guérin (BCG) to include patients with BCG-unresponsive non-muscle-invasive bladder cancer with high-grade papillary-only tumors. The previous indication was limited to patients with carcinoma in situ, with or without papillary tumors. 
• Supporting Evidence: The expanded indication was supported by previously reported results from Cohort A of the QUILT-3.032 trial, in which the combination demonstrated durable complete responses. The FDA determined that these findings could be extrapolated to patients with high-grade papillary-only disease based on overlapping clinical and biological characteristics. 
• Clinical Relevance: The expanded indication provides another treatment option for patients with BCG-unresponsive high-grade papillary-only non-muscle-invasive bladder cancer, a population previously excluded from the approved indication for nogapendekin alfa inbakicept-pmln plus BCG.

The US Food and Drug Administration (FDA) has expanded the approval of nogapendekin alfa inbakicept (Anktiva; Altor BioScience) in combination with Bacillus Calmette-Guérin (BCG) to include patients with BCG-unresponsive non-muscle-invasive bladder cancer with high-grade papillary-only tumors.

This approval, supported by a review of existing clinical and scientific evidence, including previously reported findings from Cohort A of the QUILT-3.032 trial, broadens the previous indication, which was limited to patients with BCG-unresponsive non-muscle-invasive bladder cancer containing carcinoma in situ, with or without papillary tumors.

In this multicenter, single-arm trial, researchers enrolled 77 patients with BCG-unresponsive, high-risk non-muscle-invasive bladder cancer with carcinoma in situ, with or without Ta/T1 papillary disease, who underwent resection. Patients received intravesical nogapendekin alfa inbakicept plus BCG as induction, followed by maintenance for up to 37 months. 

The primary end point was complete response, assessed via cystoscopy, urine cytology, and biopsy. Key secondary end points included duration of response and safety.

At analysis, the complete response rate was 62%. Among patients who achieved a complete response, 58% maintained their response for at least 12 months, while 40% maintained their response for at least 24 months.

Although the original efficacy population included patients with carcinoma in situ, the FDA determined that the findings could support treatment of patients with high-grade papillary-only disease. The agency's decision was based on similarities between high-grade papillary tumors and carcinoma in situ, including their aggressive clinical behavior and elevated risks of recurrence and progression following BCG treatment.

The FDA also noted that these tumor types frequently occur together and may present challenges in pathological differentiation. Based on their overlapping clinical and nonclinical characteristics, the agency concluded that efficacy established in BCG-unresponsive non-muscle-invasive bladder cancer containing carcinoma in situ could be extrapolated to high-grade papillary-only disease.

The recommended induction regimen is 400 mcg of nogapendekin alfa inbakicept administered intravesically with BCG once weekly for 6 weeks. Patients with residual carcinoma in situ and/or high-grade Ta tumors at 3 months may receive a second induction course. Following induction, maintenance treatment consists of 400 mcg of nogapendekin alfa inbakicept administered intravesically with BCG once weekly for 3 weeks at months 4, 7, 10, 13, and 19. 

For patients without evidence of high-grade disease at month 25 and beyond, additional maintenance courses may be administered once weekly for 3 weeks at months 25, 31, and 37. Treatment should be discontinued in patients with persistent disease following a second induction course, disease recurrence or progression, or unacceptable toxicity. The maximum treatment duration is 37 months.

The most common adverse reactions and laboratory abnormalities occurring in at least 15% of patients included increased creatinine, dysuria, hematuria, urinary frequency, micturition urgency, urinary tract infection, increased potassium, musculoskeletal pain, chills, and pyrexia. 

The prescribing information also warns that delaying cystectomy may allow bladder cancer to progress to metastatic disease, which can be fatal. 

The FDA is working to finalize guidance addressing the development of treatments for BCG-unresponsive non-muscle-invasive bladder cancer, including the use of existing clinical evidence to support indications across different high-risk tumor presentations. 

Source: 

US Food and Drug Administration. FDA approves an expanded indication for nogapendekin alfa inbakicept-pmln for BCG-unresponsive non-muscle invasive bladder cancer. Accessed on: October 14, 2026. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-expanded-indication-nogapendekin-alfa-inbakicept-pmln-bcg-unresponsive-non-muscle