FDA Receives sBLA for Nogapendekin Alfa Inbakicept in Papillary NMIBC

Papillary NMIBC | Image Credit: © Sebastian Kaulitzki – stock.adobe.com

The FDA has received a supplemental biologics license application (sBLA) seeking the approval of nogapendekin alfa inbakicept-pmln (Anktiva) for the treatment of patients with Bacillus Calmette–Guérin (BCG)–unresponsive non–muscle-invasive bladder cancer (NMIBC) with papillary disease.1

Additionally, ImmunityBio—the developer of nogapendekin alfa inbakicept—has submitted an expanded access protocol for nogapendekin alfa inbakicept for the management of lymphopenia.

The sBLA is supported by data from the phase 2/3 QUILT-3.032 trial (NCT0302285). In the study, patients with papillary NMIBC (n = 72) were enrolled in cohort B, where they received nogapendekin alfa inbakicept in combination with BCG.2 Data published in NEJM Evidence demonstrated that, at a median follow-up of 20.7 months (range, 2.9-37.1), patients achieved a median disease-free survival (DFS) of 19.3 months (95% CI, 7.4-not reached). The 12-, 18-, and 24-month DFS rates were 55.4% (95% CI, 42.0%-66.8%), 51.1% (95% CI, 37.6%-63.1%), and 48.3% (95% CI, 34.5%-60.7%), respectively.

Previously reported findings from QUILT-3.032 supported the April 2024 FDA approval of nogapendekin alfa inbakicept in combination with BCG for the treatment of adult patients with BCG-unresponsive NMIBC with carcinoma in situ (CIS) with or without papillary tumors.3 These data showed that patients treated with the combination (n = 77) experienced a complete response (CR) rate of 62% (95% CI, 51%-73%), and 58% of patients with a CR achieved a duration of response (DOR) of at least 12 months. Forty percent of patients with a CR had a DOR lasting at least 24 months.

Deep Dive Into QUILT-3.032

The registrational, pivotal, open-label, single-arm, 3-cohort, multicenter trial enrolled patients at least 18 years of age with histologically confirmed BCG-unresponsive CIS with or without Ta/T1 papillary disease to cohorts A and C; patients with histologically confirmed BCG-unresponsive high-grade Ta/T1 papillary NMIBC were included in cohort B.2

All patients needed to be free from resectable disease after transurethral resection of bladder tumor, and patients with high-grade Ta an/or T1 disease needed complete resection before receiving study treatment.

Patients were excluded from the study if they had a life expectancy of less than 2 years; inadequate organ function; clinical signs of severe cardiac dysfunction; and a history or evidence of muscle-invasive, locally advanced, metastatic, and/or extravesical bladder cancer. Any other cancer within the past 5 years, other than non-melanoma skin cancer, disqualified patients from enrollment.

In cohorts A and B, patients received nogapendekin alfa inbakicept at 400 µg in combination with BCG at 50 mg administered via a urinary catheter once per week for 6 consecutive weeks. In cohort C, patients received nogapendekin alfa inbakicept alone at the same dose and schedule. Patients who did not achieve a response and did not have T1 or greater disease following treatment were allowed to undergo re-induction.

The primary end points of the study were 3- and 6-month CR rate for cohorts A and C; and 12-month DFS rate for cohort B.

Additional Efficacy and Safety Details

Further findings from cohort B showed that 7% of patients underwent cystectomy.

The 12-, 18-, and 24-month progression-free survival rates were 97.1% (95% CI, 88.8%-99.3%), 94.8% (95% CI, 84.3%-98.3%), and 88.8% (95% CI, 74.1%-95.4%), respectively. The disease-specific survival rates were 100% (95% CI, 100%-100%) at 12 months and 97.7% (95% CI, 84.6%-99.7%) at 24 months.

The 12-, 18-, and 24-month overall survival rates were 98.6% (95% CI, 90.2%-99.8%), 94.3% (95% CI, 82.9%-98.1%), and 91.7% (95% CI, 79.0%-96.9%), respectively.

Regarding safety, grade 1/2 treatment-emergent adverse effects (TEAEs) were reported in 86% of patients in cohorts A and B treated with nogapendekin alfa inbakicept plus BCG (n = 161). The rates of grade 3, grade 4, and grade 5 TEAEs were 20%, 2%, and 1%, respectively. The grade 5 TEAE was cardiac arrest with an outcome of death. Two percent of patients experienced a grade 3 immune-related TEAE.

The most common grade 3 TEAEs were hematuria and urinary tract infection, which were both reported in 2% of patients. All other grade 3 TEAEs occurred at rates of 1%.

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, 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
3. FDA approves nogapendekin alfa inbakicept-pmln for BCG-unresponsive non-muscle invasive bladder cancer. FDA. April 22, 2024. Accessed April 15, 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-nogapendekin-alfa-inbakicept-pmln-bcg-unresponsive-non-muscle-invasive-bladder-cancer