Anktiva under review in EU for BCG-unresponsive NMIBC with CIS

The European Medicines Agency (EMA) has accepted the marketing authorization application for nogapendekin alfa inbakicept-pmln (Anktiva) in combination with BCG for the treatment of patients with BCG-unresponsive non–muscle invasive bladder cancer (NMIBC) with carcinoma in situ (CIS) with or without papillary tumors, ImmunityBio announced in a news release.¹

The EMA submission is supported by data from cohort A of the ongoing QUILT 3.032 trial.

The EMA will now review the application for potential approval. If approved, the marketing authorization application would be valid in all 27 European Union member states as well as in Iceland, Liechtenstein, and Norway.

“We are encouraged by the speed in which the EMA accepted our marketing authorization application and determined it would begin its assessment of our innovative treatment for this serious condition, just 9 months after it was first approved by the FDA for use in the United States,” said Patrick Soon-Shiong, MD, Founder, Executive Chairman, and Global Chief Scientific and Medical Officer of ImmunityBio, in the news release.¹ “Along with our submission to the United Kingdom’s Medicines and Healthcare products Regulatory Agency (MHRA), this action by the EMA is strong evidence of the momentum for putting ANKTIVA+BCG into the hands of physicians who are treating patients with NMIBC.”

The EMA submission is supported by data from cohort A of the ongoing QUILT 3.032 trial (NCT03022825), in which the combination of Anktiva plus BCG demonstrated a complete response (CR) rate of 71% (95% CI, 59.6-80.3) among the 100 patients enrolled in the cohort.²

Among the responders, the duration of response (DOR) ranged as long as 54 months. According to the company, this exceeded the threshold for meaningful clinical results per a panel of experts at the International Bladder Cancer Group.

Data previously reported from the first 84 patients showed that among those with a CR at 24 months, the probability of avoiding a cystectomy was 89.2%, and the probability of disease-specific survival was 100%, per Kaplan-Meier estimates.³

Overall, the phase 2/3, open-label, multicenter study is assessing the use of Anktiva across 3 patient cohorts. Cohorts A and C in the trial include patients with BCG-unresponsive bladder CIS with or without Ta/T1 papillary tumors who received Anktiva plus BCG (cohort A) or Anktiva alone (cohort C). The trial also enrolled patients with BCG-unresponsive high-grade Ta/T1 papillary NMIBC who received N-803 plus BCG in cohort B.

The primary end point for the trial is the incidence of complete response at 3 and 6-month timepoints for cohorts A and C, and disease-free survival at 12 months for cohort B. Secondary end points for cohort A are durability, cystectomy avoidance, progression-free survival, disease-specific survival, and overall survival.⁴

Anktiva was approved in the US in April 2024 for use in combination with BCG in the treatment of patients with BCG-unresponsive NMIBC with CIS with or without papillary tumors. Earlier this month, ImmunityBio announced plans to submit a supplemental biologics license application to the FDA in 2025 for an additional approval of Anktiva for patients with BCG-unresponsive NMIBC in the papillary indication (cohort B).

Additional data from QUILT 3.032

Data from all 3 cohorts in the QUILT 3.032 trial were published in NEJM Evidence in November 2022.³ Findings from cohort A encompassed the first 84 patients enrolled and treated in the phase 2/3 study.

In cohort B (n = 72), the disease-free survival (DFS) rate was 55.4% (95% CI, 42% - 66.8%) at 12 months, with a median DFS of 19.3 months (95% CI, 7.4 months – not reached), per Kaplan-Meier.

In cohort C, data showed that 20% of patients achieved a CR at 3-month follow-up. Only 1 patient maintained a CR at 6 months. Six patients underwent reinduction. The median follow-up for all patients was 7.9 months at the time of data cutoff.

Regarding safety, 86% of treatment-emergent adverse events (TEAEs) from the combination therapy were grade 1 to 2, with 3 total grade 3 immune-related TEAEs.

The QUILT 3.023 study remains ongoing, with final study completion expected in October 2028.⁴

References

1. ImmunityBio announces European Medicines Agency acceptance of marketing authorization application for ANKTIVA for the treatment of patients with BCG-unresponsive non-muscle invasive bladder cancer carcinoma in situ. News release. ImmunityBio, Inc. Published online and accessed January 27, 2025. https://immunitybio.com/immunitybio-announces-european-medicines-agency-acceptance-of-marketing-authorization-application-for-anktiva-for-the-treatment-of-patients-with-bcg-unresponsive-non-muscle-invasive-bladder-canc/

2. 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 27, 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/

3. 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

4. QUILT-3.032: A multicenter clinical trial of intravesical bacillus calmette-guerin (BCG) in combination with ALT-803 (N-803) in patients with BCG unresponsive high grade non-muscle invasive bladder cancer. ClinicalTrials.gov. Last updated April 8, 2024. Accessed November 19, 2024. https://clinicaltrials.gov/study/NCT03022825