FDA Expands ANKTIVA Approval to High-Grade Papillary-Only Bladder Cancer

ImmunityBio announced on October 14, 2026, that the U.S. Food and Drug Administration (FDA) expanded the approval of ANKTIVA® (nogapendekin alfa inbakicept-pmln), administered with Bacillus Calmette-Guérin (BCG), to include adults with BCG-unresponsive, high-grade non-muscle-invasive bladder cancer (NMIBC) with papillary-only tumors. The decision broadens the April 2024 indication, which covered carcinoma in situ (CIS), with or without papillary tumors. ANKTIVA is the first FDA-approved treatment specifically for this papillary-only population.

Regulatory Rationale: Extending Evidence Across Tumor Types

The FDA based the expansion on its review of available scientific information, concluding that efficacy previously demonstrated in CIS-containing disease could be extrapolated to high-grade papillary-only NMIBC. Although the two histologic types have different growth architectures, the FDA identified overlapping clinical and nonclinical features. Both are aggressive urothelial carcinomas, frequently coexist, can be difficult to distinguish pathologically and carry substantial risks of recurrence and progression when BCG treatment fails.

The regulatory decision followed a supplemental biologics license application supported by QUILT-3.032 Cohort B results and a literature-based rationale. The FDA’s public approval summary, however, emphasizes extrapolation from the established CIS efficacy findings rather than presenting separate papillary-only response estimates. This distinction is important when interpreting the evidence supporting the broader indication.

Clinical Evidence: QUILT-3.032

QUILT-3.032 (NCT03022825) is an open-label, single-arm, multicenter Phase 2/3 trial sponsored by ImmunityBio. The original CIS indication was supported by Cohort A, which included 77 patients with BCG-unresponsive, high-risk NMIBC with CIS, with or without Ta/T1 papillary disease, following transurethral resection.

Patients received intravesical ANKTIVA with BCG, initially once weekly for six weeks, followed by maintenance treatment for up to 37 months. The complete-response rate was 62% (95% confidence interval [CI], 51–73). Among responders, 58% maintained a response for at least 12 months and 40% for at least 24 months.

The supplemental application also included Cohort B, which evaluated patients with high-grade papillary-only disease. In its May 2026 announcement, ImmunityBio reported a 12-month disease-free survival rate of 58.2% (95% CI, 46.6–68.2) among 80 patients. These company-reported results provide additional clinical context, although they should not be conflated with Cohort A’s complete-response endpoint or interpreted as comparative evidence against other treatments.

Safety Profile and Treatment Considerations

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

ANKTIVA is administered directly into the bladder with BCG. The prescribing information warns that delaying cystectomy can allow bladder cancer to progress to metastatic disease, which can be lethal. Cystectomy should be reconsidered when high-grade disease persists after a second induction course. The expanded indication does not remove the need for appropriate surveillance or timely reassessment of treatment response.

Mechanism of Action

ANKTIVA is an interleukin-15 (IL-15) receptor agonist designed to stimulate immune-cell activity. Its fusion complex combines an IL-15 mutant with an IL-15 receptor-alpha domain. IL-15 signaling supports natural killer cells and T cells involved in antitumor immunity. This mechanism provides the biological rationale for the treatment, but does not independently establish the magnitude of clinical benefit in each NMIBC subgroup.

Clinical Interpretation

The expanded indication addresses an unmet need in high-grade papillary-only NMIBC following BCG failure. However, the FDA’s decision relies on extrapolating established CIS efficacy based on similarities between the tumor types, rather than publicly reported papillary-specific response estimates in the October approval summary.

Although Cohort A and Cohort B provide evidence of treatment activity, their different endpoints and single-arm designs limit comparative conclusions. The clinical value of the expansion will depend on durable disease control and bladder preservation without delaying necessary cystectomy.

References

U.S. Food and Drug Administration. FDA approves an expanded indication for nogapendekin alfa inbakicept-pmln for BCG-unresponsive non-muscle invasive bladder cancer. October 14, 2026.

ImmunityBio, Inc. FDA Expands ANKTIVA Approval for BCG-Unresponsive Non-Muscle-Invasive Bladder Cancer to Cover Both Papillary and CIS Disease. October 14, 2026.

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 ID NCT03022825