FDA approval sought for Anktiva in papillary NMIBC

ImmunityBio announced that it has submitted a supplemental biologics license application (sBLA) to the FDA seeking an expanded approval for nogapendekin alfa inbakicept-pmln (Anktiva) in combination with BCG for BCG-unresponsive non–muscle invasive bladder cancer (NMIBC) in the papillary indication.¹

The QUILT-3.032 trial is ongoing.

Anktiva was previously approved by the FDA in April 2024 for use in combination with BCG for patients with BCG-unresponsive NMIBC with carcinoma in situ (CIS) with or without papillary disease.

According to the company, “This combination immunotherapy wherein ANKTIVA rescues BCG efficacy, currently approved in the BCG-unresponsive CIS indication, may provide an effective therapeutic option for papillary patients who did not respond to BCG alone and face the prospect of a radical cystectomy.”

The sBLA is supported by data from cohort B of the pivotal QUILT-3.032 trial (NCT03022825), which assessed Anktiva in combination with BCG in patients with histologically confirmed BCG-unresponsive high-grade Ta/T1 papillary NMIBC.² The median age of patients in this cohort was 72 years (range, 46 to 93 years). The primary end point was disease-free survival (DFS).

Overall, the study found a DFS of 55.4% (95% CI, 42.0% to 66.8%) at 12 months, 51.1% (95% CI, 37.6% to 63.1%) at 18 months, and 48.3% (95% CI, 34.5% to 60.7%) at 24 months, per Kaplan-Meier estimates. The median DFS was 19.3 months (95% CI, 7.4 to NR).

Progression-free survival (PFS) was 97.1% (95% CI, 88.8% to 99.3%) at 12 months, 94.8% (95% CI, 84.3% to 98.3%) at 18 months, and 88.8% (95% CI, 74.1% to 95.4%) at 24 months. Overall survival was 98.6% (95% CI, 90.2% to 99.8%) at 12 months, 94.3% (95% CI, 82.9% to 98.1%) at 18 months, and 91.7% (95% CI, 79.0% to 96.9%) at 24 months. Disease-specific survival was 100% (95% CI, 100% to 100%) and 97.7% (95% CI, 84.6% to 99.7%) at 12 and 24 months, respectively.

At a median follow-up of 20.7 months (range, 2.9 to 37.1), the cystectomy rate was 7% (5 of 72).

According to ImmunityBio, “In 88% and 82% of subjects, the probability of avoiding surgical removal of the bladder was achieved for as long as 2 and 3 years, respectively, following treatment with ANKTIVA plus BCG.”

The majority (86%) of treatment-emergent adverse events (TEAEs) were grade 1 to 2. According to the authors, “The most frequently reported TEAEs for patients who received BCG plus NAI (cohorts A and B, n=161) were those expected for intravesical instillation of BCG and included dysuria, pollakiuria, and hematuria.”

The most common grade 3 TEAEs included hematuria (2%) and urinary tract infection (2%).

Overall, the QUILT-3.032 trial enrolled patients across 3 study cohorts. Cohorts A and C in the trial included patients with BCG-unresponsive bladder CIS with or without Ta/T1 papillary tumors who received Anktiva plus BCG (cohort A) or Anktiva alone (cohort C). The trial also enrolled patients with BCG-unresponsive high-grade Ta/T1 papillary NMIBC who received Anktiva plus BCG (cohort B).

The QUILT-3.032 trial is ongoing, with final completion expected in March 2029.³

REFERENCES
1. ImmunityBio announces FDA submissions of supplemental BLA for NMIBC papillary disease and for expanded access of ANKTIVA to treat lymphopenia. News release. ImmunityBio. April 15, 2025. Accessed April 15, 2025. https://immunitybio.com/immunitybio-announces-fda-submissions-of-supplemental-bla-for-nmibc-papillary-disease-and-for-expanded-access-of-anktiva-to-treat-lymphopenia/

2. Chamie K, Chang SS, Kramolowky 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

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. Last updated April 13, 2025. Accessed April 15, 2025. https://clinicaltrials.gov/study/NCT03022825