FDA Approves Nogapendekin Alfa Inbakicept Plus BCG for BCG-Unresponsive NMIBC


The FDA has approved nogapendekin alfa inbakicept-pmln plus BCG for BCG-unresponsive non–muscle-invasive bladder cancer with carcinoma in situ with or without papillary tumors.



The FDA has approved nogapendekin alfa inbakicept-pmln (Anktiva; N-803) in combination with Bacillus Calmette–Guérin (BCG) for the treatment of adult patients with BCG-unresponsive non–muscle invasive bladder cancer (NMIBC) with carcinoma in situ (CIS) with or without papillary tumors.

The regulatory decision was supported by data from the phase 2/3 QUILT-3.032 trial (NCT0302285), which demonstrated that patients treated with the combination (n = 77) experienced a complete response (CR) rate of 62% (95% CI, 51%-73%). Additionally, 58% of patients who achieved a CR had a duration of response (DOR) of at least 12 months, and 40% of patients with a CR had a DOR of at least 24 months.

In May 2023, the FDA issued a complete response letter to the initial biologics license application (BLA) for N-803. In the letter, the regulatory agency cited deficiencies related to the pre-license inspection of ImmunityBio’s third-party contract manufacturing organizations as the reason the application could not be approved in its prior form.2 The BLA was resubmitted in October 2023.3

Notably, the CRL did not request additional preclinical or phase 3 clinical trials evaluating N-803 plus BCG, updated data on DOR and safety from QUILT 3.032 were requested.

Findings from cohort A of QUILT 3.032 presented at the 2022 ASCO Annual Meeting demonstrated that at a median follow-up of 23.9 months, N-803 plus BCG experienced a CR rate of 71% (95% CI, 59.6%-80.3%). in patients with BCG-unresponsive NMIBC who experienced disease progression on prior treatment (n = 82). The median DOR was 26.6 months 95% CI, 9.9-not reached). The 12-, 18-, and 24-month DOR rates were 61.6% (95% CI, 47.3%-73.1%), 56.3% (95% CI, 41.5%-68.8%), and 53.2% (95% CI, 38.0%-66.2%), respectively.4

Cohort A included patients with histologically confirmed persistent or recurrent NMIBC with CIS with or without recurrent Ta/T1 disease who received adequate BCG within the past 12 months. Cohort B featured patients with papillary disease.

All patients received 50 mg of BCG plus 400 µg of intravesical N-803 once per week for 6 weeks.

The most common adverse effects reported in at least 15% of patients, included increased creatinine, dysuria, hematuria, urinary frequency, micturition urgency, urinary tract infection, increased potassium, musculoskeletal pain, chills, and pyrexia.1


  1. FDA approves nogapendekin alfa inbakicept-pmln for BCG-unresponsive non-muscle invasive bladder cancer. FDA. April 22, 2024. Accessed April 22, 2024.
  2. US Securities and Exchange Commission. Form 8-K. May 9, 2023. Accessed April 22, 2024.
  3. FDA accepts ImmunityBio’s BLA resubmission as complete and sets new PDUFA date. News release. ImmunityBio. October 26, 2023. Accessed April 22, 2024.
  4. Chamie K, Chang SS, Gonzalgo M, et al. Final clinical results of pivotal trial of IL-15RαFc superagonist N-803 with BCG in BCG-unresponsive CIS and papillary nonmuscle-invasive bladder cancer (NMIBC). J Clin Oncol. 2022:40(suppl 16):4508. doi:10.1200/JCO.2022.40.16_suppl.4508
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