EU/UK Approvals Sought for Nogapendekin Alfa Inbakicept Plus BCG in BCG-Unresponsive NMIBC With CIS

Marketing authorization applications (MAAs) for nogapendekin alfa inbakicept (Anktiva) plus Bacillus Calmette–Guérin (BCG) in adult patients with BCG-unresponsive non–muscle-invasive bladder cancer (NMIBC) with carcinoma in situ (CIS), with or without papillary tumors, have been submitted to the European Union’s European Medicines Agency and the United Kingdom’s Medicines and Healthcare Products Regulatory Agency.1

The combination was evaluated in the phase 2/3 QUILT-3.032 trial (NCT03022825), where it elicited a complete response (CR) rate of 62% (95% CI, 51%-73%) in evaluable patients (n = 77).2 Moreover, 58% of responders experienced a response that lasted at least 12 months and 40% had a response that lasted for at least 24 months. These data supported the FDA’s decision to approve the regimen for this population in April 2024.3

“The submission of our applications to EMA and MHRA represents a significant milestone in our efforts to address this critical need and improve patient outcomes globally,” Patrick Soon-Shiong, MD, founder, executive chairman and global chief scientific and medical officer of ImmunityBio, stated in a news release.1

A Deep Dive Into QUILT-3.032: Population, Treatment, Objectives

The single-arm, multicenter trial included patients with BCG-unresponsive, high-risk NMIBC with CIS with or without Ta/T1 papillary disease after transurethral resection.2 Those with a history of or evidence of muscle invasive, locally advanced, metastatic, and/or extravesical bladder cancer, were excluded.

Study participants received nogapendekin alfa inbakicept at 400 mcg with BCG weekly for 6 consecutive weeks in the induction period, followed by once a week, every 3 weeks at 4, 7, 10, 13, and 19 months for those with low-grade or no disease. Those who had persistent CIS or high-grade Ta disease at 3 months were able to have a second course of induction treatment. Those with ongoing CR at 25 months were able to have additional instillations once a week, every 3 weeks at months 25, 31, and 37.

Major efficacy outcome measures included CR at any time and duration of response.

The median patient age was 73 years (range, 50-91). Most patients were male (86%), White (90%), and had an ECOG performance status of 0 (83%) at baseline. With regard to tumor characteristics, 69% of patients had CIS without Ta/T1 papillary disease at the time of study entry, 21% had CIS with Ta papillary disease, and 10% had CIS with T1 ± Ta papillary disease. At baseline, the high-risk disease status was refractory for 43% of patients and relapsed for 57% of patients.

Patients had received a median of 12 prior doses of BCG, with a range of 8 to 45 doses, and 13% of patients had received a prior partial-dose of BCG. The baseline cystoscopy imaging modality was white light for 57% of patients or blue light or narrow band imaging for 40% of patients; this information was unknown for 3% of patients.

Updated Efficacy Report

Following enrollment of the 100th patient after the agent was approved by the FDA, updated data from the trial indicated that nogapendekin alfa inbakicept plus BCG elicited a CR rate of 71% in the expanded patient cohort, with responses ranging up to 54 months.4

Safety Spotlight

The safety of nogapendekin alfa inbakicept was examined in cohort A of the trial (n = 88). The median number of doses received was 12 (range, 2-30) and the median duration of exposure was 7.1 months (range, 0.26-36.3).

Sixteen percent of patients experienced serious adverse effects (AEs) with the regimen. Thirty-four percent of patients experienced AEs that required dose interruption and 7% experienced AEs that ultimately led to permanent treatment discontinuation. Although dose reductions due to AEs were not permitted for nogapendekin alfa inbakicept, 3.4% of patients required dose reductions of BCG.

The most common all-grade AEs experienced by at least 15% of patients in cohort A who received the regimen were dysuria (32%), hematuria (32%), urinary frequency (27%), micturition urgency (25%), urinary tract infection (UTI; 24%), musculoskeletal pain (17%), chills (15%), and pyrexia (15%). The most common grade 3 or 4 AEs were hematuria (3.4%), UTI (2.3%), and musculoskeletal pain (2.3%).

Looking Ahead

The assessment of both MAAs is expected to be completed by the fourth quarter of this year, according to a news release issued by ImmunityBio, Inc.1 The company noted that it is in “continued dialog for requests for information from the two agencies, with the potential of approval by 2026.”

References

1. ImmunityBio provides regulatory update on global submission for Anktiva + BCG in BCG unresponsive non-muscle invasive bladder cancer with carcinoma in situ in Europe and United Kingdom. News release. ImmunityBio, Inc. January 15, 2025. Accessed January 15, 2025. https://ir.immunitybio.com/news-releases/news-release-details/immunitybio-provides-regulatory-update-global-submission-anktiva?field_nir_news_date_value[min]=
2. Anktiva. Prescribing information. Altor BioScience, LLC; April 2024. Accessed January 15, 2025. https://www.accessdata.fda.gov/drugsatfda_docs/label/2024/761336s000lbl.pdf
3. FDA approves nogapendekin alfa inbakicept-pmln for BCG-unresponsive non-muscle invasive bladder cancer. FDA. April 22, 2024. Accessed January 15, 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-nogapendekin-alfa-inbakicept-pmln-bcg-unresponsive-non-muscle-invasive-bladder-cancer
4. ImmunityBio completes Anktiva’s post-approval enrollment of the 100th patient in BCG unresponsive NMIBC CIS trial and reports a complete response rate of 71% with a durable duration of response ranging up to 54 months. News release. ImmunityBio. November 19, 2024. Accessed January 15, 2025. https://immunitybio.com/immunitybio-completes-anktivas-post-approval-enrollment-of-the-100th-patient-in-bcg-unresponsive-nmibc-cis-trial-and-reports-a-complete-response-rate-of-71-with-a-durable-duration-of-response/