FDA Approval Expands Anktiva to BCG-Unresponsive Papillary Bladder Cancer

The FDA has expanded the approval of nogapendekin alfa inbakicept-pmln (Anktiva; Altor BioScience) given with Bacillus Calmette-Guérin (BCG) to include adults with high-grade papillary-only non–muscle-invasive bladder cancer (NMIBC) that has not responded to BCG. In a news release, the agency said the combination is the first FDA-approved treatment specifically for patients with BCG-unresponsive, high-grade papillary-only disease, a group that previously fell outside the drug's labeled indication.¹

The decision also departs from how these approvals are usually built. Rather than relying on a dedicated efficacy analysis in papillary-only disease, the FDA applied the evidence behind the drug's April 22, 2024, approval for BCG-unresponsive NMIBC with carcinoma in situ (CIS), with or without papillary tumors. The agency pointed to clinical and laboratory evidence that CIS and high-grade papillary tumors often occur together, can be difficult to tell apart under a microscope, and carry a high risk of recurrence or progression once BCG no longer works.^1,2

A New Regulatory Approach

"For Anktiva, our review of the similarities between these cancers allowed us to build on the results in patients with CIS and expand treatment options for people with high-grade papillary tumors alone," R. Angelo de Claro, MD, director of the FDA's Oncology Center of Excellence, said in the announcement. The agency added that it is working toward finalizing its draft guidance on developing drugs for BCG-unresponsive NMIBC, which is intended to address using CIS data to support approvals in papillary-only disease.¹

The CIS approval rested on QUILT-3.032 (NCT03022825), a phase 2/3, open-label, single-arm, multicenter trial. Among the 77 adults in the FDA's efficacy analysis, 62% achieved a complete response. Of those, approximately 58% maintained it for at least 12 months and 40% for at least 24 months.^1,3

Options in this population have been limited. Radical cystectomy can be curative but carries high morbidity and mortality, particularly among older adults, who make up most patients with NMIBC, according to the published CIS cohort results.⁴

Papillary Cohort Results

Although the FDA's announcement did not cite them as the basis for the expansion, QUILT-3.032 also enrolled a separate cohort of patients with BCG-unresponsive, high-grade Ta/T1 papillary-only NMIBC (cohort B), who received 400 μg of nogapendekin alfa inbakicept plus 50 mg of BCG intravesically weekly for 6 consecutive weeks.⁵

As of the data cutoff, disease-free survival rates at 12, 24, and 36 months were 58.2%, 52.1%, and 38.2%, respectively. Progression-free survival rates were 94.9% at 12 months and 83.1% at 36 months, and disease-specific survival rates were 98.7% and 96.0%. Cystectomy avoidance rates were 92.2% at 12 months and 81.8% at 36 months, with median time to cystectomy not reached.⁵

Administration and Safety Considerations

The treatment is instilled with BCG directly into the bladder through a catheter once weekly for 6 weeks, with additional courses based on response, for up to 37 months. Treatment should stop if cancer persists after a second 6-week course, recurs, or progresses, or if adverse effects (AEs) become unacceptable.¹ The recommended induction dose is 400 mcg intravesically with BCG.²

The most common AEs and laboratory abnormalities included painful or frequent urination, urinary urgency, hematuria, urinary tract infections, muscle or joint pain, chills, fever, and elevated serum creatinine and potassium, giving pharmacists concrete monitoring and counseling targets. The prescribing information also warns that delaying cystectomy can allow cancer to spread, which can be fatal.¹

In cohort B, most treatment-related AEs were grade 1 or 2 (61%), 3% were grade 3, and none were grade 4 or 5.⁵ In a pharmacokinetic subset of 25 patients from the earlier analysis, serum levels of the drug were below the lower limit of quantification, with no evidence of systemic exposure after intravesical administration.⁴

REFERENCES

1. FDA approves first treatment for certain people with BCG-unresponsive bladder cancer. News release. FDA. October 14, 2026. Accessed October 14, 2026. https://www.fda.gov/news-events/press-announcements/fda-approves-first-treatment-certain-people-bcg-unresponsive-bladder-cancer

2. FDA approves nogapendekin alfa inbakicept-pmln for BCG-unresponsive non-muscle invasive bladder cancer. News release. FDA. Accessed October 14, 2026. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-nogapendekin-alfa-inbakicept-pmln-bcg-unresponsive-non-muscle-invasive-bladder-cancer

3. QUILT-3.032: A multicenter clinical trial of intravesical Bacillus Calmette-Guerin (BCG) in combination with ALT-803 (N-803) in patients with BCG unresponsive high grade non-muscle invasive bladder cancer. ClinicalTrials.gov identifier: NCT03022825. Updated October 16, 2025. Accessed October 14, 2026. https://clinicaltrials.gov/study/NCT03022825

4. Chamie K, Chang SS, Kramolowsky E, et al. IL-15 superagonist NAI in BCG-unresponsive non-muscle-invasive bladder cancer. NEJM Evid. 2023;2(1). doi:10.1056/EVIDoa2200167

5. Chang SS, Chamie K, Kramolowsky E, et al. Prolonged progression-free survival, disease-free survival, and cystectomy avoidance with IL-15 receptor lymphocyte-stimulating agent NAI plus Bacillus Calmette-Guérin in Bacillus Calmette-Guérin-unresponsive papillary-only nonmuscle-invasive bladder cancer. J Urol. 2026;215(1):44-56. doi:10.1097/JU.0000000000004782