FDA Expands Anktiva Approval to Papillary-Only BCG-Unresponsive Bladder Cancer

The FDA has expanded the approval of nogapendekin alfa inbakicept-pmln (Anktiva) plus Bacillus Calmette-Guérin (BCG) to include adult patients with BCG-unresponsive non-muscle invasive bladder cancer (NMIBC) with papillary-only tumors, ImmunityBio announced on Oct. 14.¹ The label now covers patients with carcinoma in situ (CIS) with or without papillary tumors, as well as those with papillary-only disease. According to the company, it is the first FDA approval to include BCG-unresponsive NMIBC with papillary-only tumors.¹

The decision came nearly three months ahead of the Jan. 6, 2027 target action date.²

What did the FDA approve?

Anktiva’s original approval in April 2024 covered BCG-unresponsive NMIBC with CIS, with or without papillary tumors.¹ For the expanded indication, FDA extrapolated efficacy from the CIS population in Cohort A of the QUILT-3.032 trial to high-grade papillary-only disease, citing overlapping clinical and nonclinical features of the two histologies.² The company’s announcement does not present separate efficacy results for patients with papillary-only disease.¹

ImmunityBio estimates that papillary disease represents approximately 85% of the NMIBC patient population.¹

“Patients with high-grade papillary disease that no longer responds to BCG remain at meaningful risk for recurrence and progression and historically have had limited nonsurgical treatment options,” said Sam S. Chang, MD, professor of urology and chief surgical officer of the Vanderbilt Ingram Cancer Center.¹

How does Anktiva work?

Anktiva is an interleukin-15 (IL-15) receptor agonist fusion complex that combines a mutant IL-15 (IL-15N72D) with an IL-15 receptor alpha IgG1 fusion protein. It binds IL-15 receptors on natural killer (NK) cells and T cells.¹ It is administered intravesically, meaning it is delivered directly into the bladder, in combination with BCG. ImmunityBio says the molecule activates NK cells and supports the generation of memory killer T cells, which the company credits with helping to sustain complete responses.¹

The role of immune memory in durable cancer control has come up in previous BioPharm International® coverage. In a video interview on cancer vaccines, Eric von Hofe, PhD, chief executive officer of CellxLife, described what a lasting immune response can offer. “Once you mount a successful immune response, that will then, for your lifelong, be there policing,” von Hofe said.

What data support the expansion?

In Cohort A of QUILT-3.032, 62% of 77 patients with BCG-unresponsive CIS achieved a complete response.¹ Among responders, 58% maintained their response for at least 12 months and 40% for at least 24 months.¹

Most treatment-related adverse events were bladder instillation effects, including dysuria, urinary frequency, and hematuria, and were mostly grade 1 to 2.¹ The label warns that delaying cystectomy can lead to metastatic bladder cancer, which can be lethal.¹

“This approval marks an important expansion of Anktiva plus BCG for patients with BCG-unresponsive NMIBC and advances our goal of harnessing the patient’s own immune system to achieve durable, tumor-free outcomes,” said Patrick Soon-Shiong, MD, founder, executive chairman, and global chief scientific and medical officer of ImmunityBio.¹

How did the application reach approval?

The papillary indication followed a difficult regulatory path. FDA issued a refuse-to-file letter for ImmunityBio’s supplemental application in May 2025.² FDA had previously told the company that because disease-free survival is a time-to-event endpoint, a randomized trial was required for the papillary-only setting.² ImmunityBio refiled in March 2026, and FDA accepted the application in May 2026.²

Why does this patient population matter?

The American Cancer Society estimates approximately 84,530 new bladder cancer cases and 17,870 deaths in the US in 2026, with men accounting for about 64,730 of those new cases.³

Other immunotherapy combinations with BCG are also in development for high-risk NMIBC. In exploratory analyses of the POTOMAC trial, AstraZeneca’s durvalumab (Imfinzi) plus BCG reduced early recurrence risk in high-risk NMIBC.

References

1. ImmunityBio. FDA Expands ANKTIVA Approval for BCG-Unresponsive Non-Muscle Invasive Bladder Cancer to Cover Both Papillary and CIS Disease. Press release. Published October 14, 2026. Accessed October 15, 2026.
2. Liu A. FDA clears ImmunityBio’s Anktiva expansion in bladder cancer after regulatory whiplash. Fierce Pharma. Published October 14, 2026. Accessed October 15, 2026.
3. American Cancer Society. Key Statistics for Bladder Cancer. Accessed October 2026.