QUILT 3.032 trial: Anktiva achieves high response rate in BCG-unresponsive NMIBC

Nogapendekin alfa inbakicept-pmln (Anktiva; N-803) plus BCG demonstrated a high rate of complete response in patients with BCG-unresponsive non–muscle-invasive bladder cancer (NMIBC) with carcinoma in situ (CIS), according to updated data from the ongoing QUILT 3.023 trial (NCT03022825).¹

The QUILT 3.023 study remains ongoing to assess the durability of response and overall survival.

The preliminary findings, shared in a news release by ImmunityBio, encompass the first 100 patients enrolled and treated in the phase 2/3 study. At the time of data cutoff (November 2024), 71% of patients achieved a complete response following treatment. Among the responders, the duration of response ranged as long as 54 months.

According to ImmunityBio, “This data update will be submitted to the European Medicines Agency (EMA) in a Marketing Authorization Application (MAA) for ANKTIVA in the European Union (EU), which is anticipated during Q4 2024.”

The agent was approved by the FDA in April 2024.

“We are encouraged by the consistent complete response rates observed in our expanded patient cohort,” said Patrick Soon-Shiong, MD, executive chairman and global chief scientific and medical officer of ImmunityBio, in the news release.¹ “These results highlight the potential of ANKTIVA to transform the treatment landscape for patients with BCG-unresponsive NMIBC CIS, offering hope for improved outcomes and cystectomy avoidance, especially with the prolonged duration of response now ranging as much as 54 months in this 100-patient analysis. Duration of complete response is the key efficacy element in driving cystectomy avoidance in this BCG-unresponsive population. I am pleased that this updated ANKTIVA data confirms that one of the highest durable responses is achieved when compared to other approved products in this indication.”

Overall, the phase 2/3, open-label, multicenter study is assessing the use of N-803 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 N-803 plus BCG (cohort A; n = 84) or N-803 alone (cohort C; n = 10). The trial also enrolled patients with BCG-unresponsive high-grade Ta/T1 papillary NMIBC who received N-803 plus BCG in cohort B (n = 77).

Findings from cohort B of the study were the basis of the approval for the agent earlier this year.

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.²

Previous data on the QUILT-3.032 trial were published in NEJM Evidence in November 2022.³

In cohort A, 71% (95% CI, 59.6% – 80.3%) of patients achieved a CR with a median follow-up of 23.9 months. The median duration of CR was 26.6 months (95 CI, 9.9 months – not reached). 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.

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). At the time of the FDA approval, the complete response rate was 62% to 73% among the 77 evaluable patients included in the analysis. The duration of complete response was longer than 47 months at the time of data cutoff, which exceeded the threshold for meaningful clinical results per a panel of experts at the International Bladder Cancer Group. Among patients with a complete response, 58% demonstrated a duration of response (DOR) of 12 months or longer, and 40% demonstrated a DOR of 24 months or longer.

In cohort C, data from the published study in 2022 showed that 20% of patients achieved a complete response 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 grade 3 immune-related TEAEs.

The QUILT 3.023 study remains ongoing to assess the durability of response and overall survival. Final study completion is expected in October 2028.²

References

1. 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. Published online and accessed November 19, 2024. https://www.businesswire.com/news/home/20241119975432/en/ImmunityBio-Completes-ANKTIVA%E2%80%99s-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

2. 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

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