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

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

References

1. FDA approves nogapendekin alfa inbakicept-pmln for BCG-unresponsive non-muscle invasive bladder cancer. FDA. April 22, 2024. Accessed April 22, 2024. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-nogapendekin-alfa-inbakicept-pmln-bcg-unresponsive-non-muscle-invasive-bladder-cancer
2. US Securities and Exchange Commission. Form 8-K. May 9, 2023. Accessed April 22, 2024. https://ir.immunitybio.com/static-files/307bb4e5-4082-4b4d-9f39-edbb7943ee51
3. FDA accepts ImmunityBio’s BLA resubmission as complete and sets new PDUFA date. News release. ImmunityBio. October 26, 2023. Accessed April 22, 2024. https://immunitybio.com/fda-accepts-immunitybios-bla-resubmission-as-complete-and-sets-new-pdufa-date/
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