FDA Approves Nogapendekin Alfa-inbakicept/BCG in BCG-unresponsive NMIBC


Nogapendekin alfa-inbakicept is now approved for the treatment of patients with BCG-unresponsive non-muscle invasive bladder cancer.

This approval is based on the results of the phase 2/3 QUILT-3.032 trial (NCT03022825).

This approval is based on the results of the phase 2/3 QUILT-3.032 trial (NCT03022825).

The FDA has approved nogapendekin alfa-inbakicept (Anktiva) in combination with Bacillus Calmette-Guérin (BCG) as a treatment for patients with BCG-unresponsive, non-muscle invasive bladder cancer (NMBIC) with carcinoma in-situ, according to a press release from the agency.1


This approval is based on the results of the phase 2/3 QUILT-3.032 trial (NCT03022825). This trial assessed the treatment combination in patients with BCG-unresponsive NMIBC.

In the QUILT-3.032 trial, the overall complete response (CR) rate was 71.0% (95% CI, 59.6%-80.3%) in cohort A, which included patients treated with intravesical nogapendekin plus BCG.2 At the 3-month, 6-month, and 12-month response assessments, CR rates were 55% (95% CI, 43.5%-65.9%), 56% (95% CI, 44.7%-67.0%), and 45% (95% CI, 34.1%-56.5%), respectively.

The median duration of CR in those who experienced a response to treatment was 26.6 months (95% CI, 9.9-not reached [NR]). At the time of the data cutoff, 28 patients still had ongoing CRs. Of note, 2 patients who had initial CRs were reported at about 9 months because of COVID-19 or other illnesses that delayed the 6-month visit.

In cohort B, which included patients with BCG-unresponsive high-grade Ta/T1 papillary NMIBC, the estimated 12-month, 18-month, and 24-month disease-free survival (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. Investigators also highlighted a median DFS of 19.3 months (95% CI, 7.4-NR) in this cohort.

In cohort C, the median time of data cutoff was 7.9 months. At 3 months, 20% of patients achieved a CR, and 10 were given nogapendekin alone. Additionally, 6 patients had reinduction, and 1 maintained a CR at 6 months.


In this open-label, multicenter study, patients with histologically confirmed BCG-unresponsive carcinoma in situ with or without Ta/T1 papillary disease were enrolled in cohorts A (n = 84) and C (n = 10), and patients with histologically confirmed BCG-unresponsive high-grade Ta/T1 papillary NMIBC were enrolled in cohort B (n = 77). Patients in cohorts A and B were assigned intravesical nogapendekin at 400 μg/instillation plus intravesical BCG at 50 mg/instillation. Patients in cohort C were assigned intravesical nogapendekin alone at 400 μg/instillation. Patients in all cohorts received weekly treatment through a urinary catheter for 6 weeks, and response assessments were conducted every 3 months for 24 months and then every 6 months from months 24 to 60.

The primary end point for cohorts A and C was the incidence of CRs at 3 and 6 months, and the primary end point for cohort B was DFS at 12 months. Secondary end points included durability of response, cystectomy avoidance rate, progression-free survival (PFS), disease-specific survival (DSS), and overall survival (OS).

Patients were eligible for enrollment if they were absent of resectable disease after transurethral resection of bladder tumor procedures, and if those with high-grade Ta/T1 disease had a complete resection prior to enrollment. Exclusion criteria included life expectancy of less than 2 years, inadequate organ function, clinical signs of severe cardiac dysfunction, and history or evidence of muscle-invasive, locally advanced, metastatic and/or extravesical bladder cancer, or any other cancer, other than nonmelanoma skin cancer, within the past 5 years.


The most common treatment-emergent adverse effects (TEAEs) in cohorts A and B were dysuria, pollakiuria, and hematuria. A total of 86% of patients in these cohorts experienced at least one grade 1/2 TEAE, 20% experienced grade 3 toxicity, 2% had a grade 4 event, and 1% had grade 5 TEAEs. Grade 3 TEAEs included hematuria (2%) and urinary tract infection (2%). A grade 5 TEAE occurred in 1 patient from cardiac arrest, and 15% of patients experienced a TEAE that resulted in hospitalization.


Prior to the approval, the FDA accepted a resubmission of a biologics license application (BLA) for the treatment combination in October 20233 after previously declining to approve the application for the combination in May after observing deficiencies related to its pre-license inspection of developers’ third-party contract manufacturing organizations.4


  1. FDA approves nogapendekin alfa inbakicept-pmln for BCG-unresponsive non-muscle invasive bladder cancer. News release. FDA. April 22, 2024. Accessed April 22, 2024. https://shorturl.at/boswH
  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). doi:10.1056/EVIDoa2200167
  3. FDA accepts ImmunityBio’s BLA resubmission as complete and sets new PDUFA date. News release. ImmunityBio, Inc. October 26, 2023. Accessed April 22, 2024. https://shorturl.at/loqMN
  4. FDA declines to approve ImmunityBio's bladder cancer therapy, shares slump. News release. ImmunityBio, Inc. May 11, 2023. Accessed January 31, 2024. bit.ly/3nSoDnj
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