Updated data from the ongoing QUILT 3.023 trial (NCT03022825) demonstrate a high complete response rate with nogapendekin alfa inbakicept-pmln (Anktiva; N-803) plus BCG in patients with BCG-unresponsive non-muscle-invasive bladder cancer (NMIBC) with carcinoma in situ (CIS). The data, which includes the first 100 patients enrolled, showed that 71% of patients achieved a complete response following treatment, with durations extending up to 54 months. This offers hope for improved outcomes and cystectomy avoidance.
QUILT 3.023 Trial Details
The QUILT 3.023 study is an ongoing phase 2/3, open-label, multicenter trial evaluating N-803 across three patient cohorts. Cohorts A and C include patients with BCG-unresponsive bladder CIS with or without Ta/T1 papillary tumors, treated with N-803 plus BCG (cohort A; n = 84) or N-803 alone (cohort C; n = 10). Cohort B (n = 77) includes patients with BCG-unresponsive high-grade Ta/T1 papillary NMIBC who received N-803 plus BCG. The primary endpoint for cohorts A and C is the incidence of complete response at 3 and 6 months, while for cohort B, it is disease-free survival at 12 months. Secondary endpoints for cohort A include durability, cystectomy avoidance, progression-free survival, disease-specific survival, and overall survival.
Efficacy Data
In cohort A, 71% of patients achieved a complete response (95% CI, 59.6% – 80.3%) with a median follow-up of 23.9 months. The median duration of complete response was 26.6 months (95% CI, 9.9 months – not reached). Among those with a complete response at 24 months, the probability of avoiding cystectomy was 89.2%, and the probability of disease-specific survival was 100%, according to Kaplan-Meier estimates.
Cohort B showed a disease-free survival (DFS) rate of 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 FDA approval, the complete response rate in cohort B was 62% to 73% among 77 evaluable patients. The duration of complete response exceeded 47 months at data cutoff, surpassing the threshold for clinically meaningful results as determined by the International Bladder Cancer Group. 58% of patients with a complete response demonstrated a duration of response (DOR) of 12 months or longer, and 40% demonstrated a DOR of 24 months or longer.
In cohort C, 20% of patients achieved a complete response at 3-month follow-up, with only one patient maintaining a CR at 6 months. Six patients underwent reinduction. The median follow-up for all patients was 7.9 months at data cutoff.
Safety Profile
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.
Future Plans
ImmunityBio plans to submit this updated data to the European Medicines Agency (EMA) in a Marketing Authorization Application (MAA) for ANKTIVA in the European Union (EU) during Q4 2024. The QUILT 3.023 study is ongoing to assess the durability of response and overall survival, with final study completion expected in October 2028.
According to Patrick Soon-Shiong, MD, executive chairman and global chief scientific and medical officer of ImmunityBio, “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... 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.”
