FDA Expands Anktiva Approval to Papillary-Only BCG-Unresponsive NMIBC

The US Food and Drug Administration (FDA) has expanded the indication for nogapendekin alfa inbakicept-pmln (Anktiva) with Bacillus Calmette-Guérin (BCG) to include adults with BCG-unresponsive, high-grade non-muscle invasive bladder cancer (NMIBC) with papillary-only tumors.

The October 14, 2026, action revises the April 2024 indication, which was limited to BCG-unresponsive NMIBC with carcinoma in situ (CIS) with or without papillary tumors. Rather than relying on a new trial, the FDA concluded that efficacy shown in patients with CIS could be extrapolated to high-grade papillary disease, and the prescribing information continues to warn that delaying cystectomy can lead to metastatic bladder cancer, which can be lethal.

What did the FDA approve, and on what basis?

The expanded label now covers adults with BCG-unresponsive NMIBC regardless of whether CIS is present, provided disease is high grade.

According to the FDA, high-grade papillary tumors and CIS have different architectural growth patterns but are both aggressive urothelial carcinomas that frequently coexist, can be difficult to distinguish pathologically, and carry a high risk of recurrence and progression in the BCG-unresponsive setting. On the basis of these overlapping clinical and nonclinical features, the agency determined that the prior demonstration of efficacy in CIS-containing disease could be applied to papillary-only disease.

The FDA noted it is working to finalize its draft guidance on drug development for BCG-unresponsive NMIBC to address this extrapolation approach. The decision arrived ahead of the January 6, 2027, Prescription Drug User Fee Act target date that ImmunityBio announced when the supplemental application was accepted in May 2026. In March 2026, the National Comprehensive Cancer Network had added the combination as a category 2A option for BCG-unresponsive papillary-only disease.

Nogapendekin alfa inbakicept-pmln is an interleukin-15 (IL-15) receptor agonist that is designed to activate and expand natural killer cells and CD8-positive T cells.

What efficacy data supported the original approval?

Efficacy was established in cohort A of QUILT-3.032 (NCT03022825), a single-arm, multicenter trial of 77 patients with BCG-unresponsive, high-risk NMIBC with CIS with or without Ta/T1 papillary disease following transurethral resection. Patients received intravesical induction with BCG, followed by maintenance therapy for up to 37 months. Complete response (CR) was assessed by cystoscopy, urine cytology, and biopsy.

• CR rate: 62% (95% CI, 51%-73%)
• Among patients with a CR, 58% had a duration of response of at least 12 months
• Among patients with a CR, 40% had a duration of response of at least 24 months

Initial results from the trial were published in NEJM Evidence.

What do the papillary-only cohort data show?

The FDA notice does not cite results from QUILT-3.032 cohort B, which enrolled patients with papillary-only disease; the agency based the expansion on extrapolation. However, cohort B outcomes were published in the Journal of Urology and formed the basis of the supplemental application. That single-arm cohort enrolled 80 patients with histologically confirmed BCG-unresponsive, high-grade Ta/T1 papillary NMIBC without CIS. The primary end point was disease-free survival (DFS) at 12 months.

• DFS: 58.2% (95% CI, 46.6%-68.2%) at 12 months, 52.1% (95% CI, 40.3%-62.7%) at 24 months, and 38.2% (95% CI, 25.6%-50.6%) at 36 months; median DFS, 25.3 months
• Progression-free survival: 94.9% at 12 months and 83.1% at 36 months
• Disease-specific survival: 98.7% at 12 months and 96.0% at 36 months
• Cystectomy avoidance: 92.2% at 12 months and 81.8% at 36 months

Because cohort B had no comparator arm, these results cannot be directly compared with outcomes from other bladder-sparing therapies.

What adverse events should nurses monitor?

The most common adverse reactions (≥15%), including laboratory abnormalities, were increased creatinine, dysuria, hematuria, urinary frequency, micturition urgency, urinary tract infection, increased potassium, musculoskeletal pain, chills, and pyrexia.

In a pooled safety population of 180 patients from cohorts A and B, grade 1 or 2 treatment-related adverse events occurred in 61% of patients and grade 3 events in 3%, with no grade 4 or 5 treatment-related events. The most frequent treatment-related events were those expected with intravesical BCG, including dysuria, urinary frequency, and hematuria.

The prescribing information includes a warning that delaying cystectomy can lead to the development of metastatic bladder cancer, which can be lethal.

How is nogapendekin alfa inbakicept-pmln dosed?

The recommended dose is 400 mcg administered intravesically with BCG once a week for 6 weeks as induction. A second induction course may be given to patients with residual CIS and/or high-grade Ta tumors at month 3. Maintenance consists of 400 mcg with BCG once a week for 3 weeks at months 4, 7, 10, 13, and 19, for a total of 15 doses. For patients with no evidence of high-grade disease at month 25 and later, maintenance instillations with BCG may be given once a week for 3 weeks at months 25, 31, and 37, for up to 9 additional instillations.

Treatment should be discontinued for disease persistence after second induction, disease recurrence or progression, or unacceptable toxicity. The maximum treatment duration is 37 months.

How does this fit into current NMIBC care?

High-risk NMIBC includes high-grade invasive tumors, CIS, and large high-grade papillary tumors, and grade and stage determined from transurethral resection pathology drive risk category and treatment planning. Until this expansion, patients with BCG-unresponsive papillary-only disease had no FDA-approved bladder-sparing option specific to that population, and radical cystectomy remained the definitive treatment.

Nursing teams already managing intravesical therapy will recognize the toxicity profile. Previous Oncology Nursing News coverage highlighted that BCG commonly causes cumulative urinary tract infection-like and flu-like symptoms, that urinalysis and new symptoms should be reviewed before each instillation, and that treatment may be held for a urine culture when infection is suspected.

Limitations include the single-arm design of both QUILT-3.032 cohorts and a cohort B population that was 74% male and 89% White, which may limit generalizability.5 QUILT-3.032 is sponsored by ImmunityBio.

What are the key takeaways for oncology nurses?

• Eligibility has broadened: Adults with BCG-unresponsive, high-grade NMIBC with papillary-only tumors are now within the labeled indication, in addition to those with CIS with or without papillary tumors.
• Explain the evidence base: Approval for papillary-only disease rests on extrapolation from CIS data rather than a new trial, which may come up in shared decision-making conversations about bladder preservation vs cystectomy.
• Reinforce surveillance: The label warns that delaying cystectomy can lead to metastatic disease; adherence to scheduled cystoscopy, cytology, and assessments is essential.
• Monitor urinary and systemic symptoms: Dysuria, hematuria, frequency, urgency, urinary tract infection, chills, and pyrexia were among the most common reactions; increased creatinine and potassium were common laboratory abnormalities.
• Plan for a long treatment course: Induction plus maintenance can extend to 37 months, with weekly instillation blocks that affect patient travel, time, and caregiver burden.

References

1. FDA approves an expanded indication for nogapendekin alfa inbakicept-pmln for BCG-unresponsive non-muscle invasive bladder cancer. News release. US Food and Drug Administration. October 14, 2026. Accessed October 14, 2026. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-expanded-indication-nogapendekin-alfa-inbakicept-pmln-bcg-unresponsive-non-muscle
2. ImmunityBio announces FDA acceptance of supplemental BLA for ANKTIVA plus BCG in BCG-unresponsive non-muscle invasive bladder cancer with papillary disease; PDUFA date set for January 6, 2027. News release. ImmunityBio, Inc. May 19, 2026. Accessed October 14, 2026. https://immunitybio.com/immunitybio-announces-fda-acceptance-of-supplemental-bla-for-anktiva-plus-bcg-in-bcg-unresponsive-non-muscle-invasive-bladder-cancer-with-papillary-disease-pdufa-date-set-for-january-6-2027/
3. ANKTIVA with BCG demonstrates 96% survival from bladder cancer at three years with median survival not yet reached in BCG-unresponsive high-grade papillary-only non-muscle invasive bladder cancer. News release. ImmunityBio, Inc. December 16, 2025. Accessed October 14, 2026. https://www.businesswire.com/news/home/20251216185945/en
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):EVIDoa2200167. 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
6. Johnson K, Bologna S. Tumor grade, risk stratification, and patient counseling. Oncology Nursing News. September 17, 2026. Accessed October 14, 2026. https://www.oncnursingnews.com/view/tumor-grade-risk-stratification-and-patient-counseling
7. Johnson K, Bologna S. Managing adverse events with intravesical therapies. Oncology Nursing News. October 8, 2026. Accessed October 14, 2026. https://www.oncnursingnews.com/view/managing-adverse-events-with-intravesical-therapies