FDA Expands Anktiva to Papillary-Only BCG-Unresponsive Bladder Cancer. The Evidence Comes From CIS Patients.
On Oct. 14 the FDA extended nogapendekin alfa inbakicept-pmln, given with BCG, to high-grade papillary-only non-muscle invasive bladder cancer. The response figures behind it come from a single-arm trial in carcinoma in situ.
The Food and Drug Administration expanded the approved use of Anktiva on Oct. 14. Nogapendekin alfa inbakicept-pmln, given with Bacillus Calmette-Guérin (BCG), is now approved for adults with high-grade papillary-only bladder cancer that has not invaded the bladder muscle and has not responded to BCG. The FDA calls it the first approved treatment specifically for BCG-unresponsive, high-grade papillary-only disease. The approval went to Altor BioScience.
Anktiva, an interleukin-15 receptor agonist, was first approved in April 2024 (BLA 761336) for BCG-unresponsive non-muscle invasive bladder cancer with carcinoma in situ (CIS), with or without papillary tumors. The new indication covers patients whose disease is papillary only. For urology clinics, it adds an intravesical option before cystectomy for a group that had none labeled specifically for it.
What the evidence is
The FDA did not cite a trial in papillary-only patients. It applied the evidence from the CIS approval, reasoning that CIS and high-grade papillary tumors often occur together, can be hard to tell apart under a microscope and carry a high risk of recurrence or progression once BCG stops working. The agency describes this as a new approach to evaluating treatments for BCG-unresponsive disease.
That evidence is QUILT-3.032 (NCT03022825), a single-arm, multicenter trial in 77 adults. According to the prescribing information, 69 percent had CIS without papillary disease, 21 percent had CIS with Ta tumors and 10 percent had CIS with T1 tumors. The complete response rate was 62 percent (95% CI, 51 to 73), meaning no high-grade cancer on follow-up. Of the 48 responders, 58 percent stayed in response for at least 12 months and 40 percent for at least 24 months. The release gives no response or durability figures for papillary-only patients, and the label's efficacy section covers only patients with CIS.
The approval rests on extrapolation from carcinoma in situ. There is no papillary-only response rate to quote to a patient.
Dosing and stopping rules
Anktiva is instilled with BCG through a catheter. The label dose is 400 mcg once a week for six weeks of induction, with a second induction course if there is no complete response at month 3. Maintenance runs three weekly instillations at months 4, 7, 10, 13 and 19, with further courses at months 25, 31 and 37 for patients still in complete response. Treatment stops for disease that persists after the second induction, recurrence or progression, unacceptable toxicity, or at 37 months.
Safety and the cystectomy warning
The most common reactions in the label (15 percent or more) were increased creatinine, painful urination, blood in the urine, urinary frequency and urgency, urinary tract infection, increased potassium, musculoskeletal pain, chills and fever. Serious adverse reactions occurred in 16 percent of the 88 patients in the safety cohort.
The label warns that delaying cystectomy can lead to muscle-invasive or metastatic cancer, which can be lethal. In QUILT-3.032, 10 percent of the 77 evaluable patients progressed to muscle-invasive disease, with a median of 107 days from persistent or recurrent CIS to progression. The label tells clinicians to reconsider cystectomy if there is no complete response after a second induction.
What the FDA said
R. Angelo de Claro, M.D., director of the FDA's Oncology Center of Excellence, said: "We listen to patients, clinicians, and researchers, and we act when the science supports a new approach." The agency says it is working to finalize its August 2024 draft guidance on BCG-unresponsive disease (docket FDA-2018-D-0342), which is intended to discuss using CIS evidence to support approvals for papillary-only disease.
Why it matters
Urologists offering Anktiva to a papillary-only patient should set the response checkpoints at the outset, since the label's stopping rules and cystectomy warning define how long surgery can reasonably wait. As of Oct. 14, the label posted on DailyMed still showed only the CIS indication, so check for the updated prescribing information. Like the lirafugratinib approval for cholangiocarcinoma, the efficacy data here come from a single-arm trial without a control group.
Reported, fact-checked and edited by The Script Pad's editorial staff.
This article is for professional education and does not replace clinical judgment. Treatment decisions should be based on the individual patient and current guidelines.
