KEY TAKEAWAYS
- The phase 2 & 3 trial aimed to investigate the efficacy of intravesical BCG plus N-803 in patients with BCG-unresponsive high-grade NMIBC.
- The primary endpoint was to determine CR.
- Researchers observed a high CRR with N-803 plus BCG in subjects failing multiple therapies, with a median response duration surpassing 28 months.
Patients with Non-muscle invasive bladder cancer (NMIBC) CIS unresponsive to BCG have limited treatment options. N-803 (Anktiva) is a mutant IL-15-based immunostimulatory fusion protein complex (IL15RaFc) that promotes proliferation and activation of natural killer (NK) cells and CD8+ T cells, but not regulatory T cells. An open-label, 3-cohort multicenter study (QUILT 3.032) of intravesical BCG plus N-803 in patients with BCG-unresponsive high-grade NMIBC (NCT03022825) was opened.
Patrick Soon-Shiong and the team aimed to report on the duration of response and the CR rate of subjects with BCG refractory, relapsed, checkpoint-failure, and chemotherapy-failure in 94 BCG-unresponsive CIS subjects.
They performed an inclusive analysis wherein all treated patients received intravesical N-803 plus BCG according to the standard induction/maintenance treatment schedule. The primary endpoint for CIS was the incidence of complete response (CR) of CIS at any time. Subset analyses were pre-planned per protocol.
About the CIS subjects: All received prior BCG, with a median of 12.0 prior BCG doses (range, 5 to 48 doses). The median time from the last prior BCG dose to the first documented CIS disease recurrence was 2.46 months (range, 0.7 to 11.1 months). 48 subjects received additional prior therapy including chemotherapy and checkpoint therapy, in addition to prior BCG therapy. In this highly pretreated group, 31 out of 48 had a CR of 65% (49.5, 77.8). 74 subjects received ≥12 prior BCG doses; 51 out of 74 had a CR, yielding a CR rate of 69% (57.1, 79.2), and 14 out of 20 subjects who received <12 doses of prior BCG had a CR rate of 70% (45.7, 88.1). A total of 53 were BCG-unresponsive/BCG-relapsed; the CR rate in this group was 72% (57.7, 83.2).
Both BCG-unresponsive/BCG-refractory and BCG-unresponsive/BCG-relapsed had CR rates comparable to the efficacy population. The median duration of response is 26.6 months (9.9, NR), with the upper end of the confidence interval not reached. By the Kaplan-Meier method, 61.3% of subjects had a duration of CR lasting >12 months and 53.2% had a duration of >24 months.
The study concluded that N-803 plus BCG demonstrated a notable increase in complete response rates (CRR) among subjects who had failed multiple therapies, including BCG, chemotherapy, and checkpoint inhibitors. Furthermore, the median duration of response exceeded 28 months, highlighting the potential of this combination therapy as an effective option for patients with NMIBC unresponsive to conventional treatments.
The study was sponsored by the ImmunityBio, Inc.
Source: https://www.auajournals.org/doi/10.1097/01.JU.0001008640.01272.9d.03
Clinical Trial: https://clinicaltrials.gov/study/NCT03022825
Shiong P S., Reddy S, Chamie K, (2024). “N-803 PLUS BCG COMPLETE RESPONSE RATE IN NMIBC CIS SUBJECTS: BCG REFRACTORY, RELAPSED, CHECKPOINT FAILURE, AND CHEMOTHERAPY FAILURE; UPDATED RESULTS (QUILT 3.032). “Presented at AUA 2024 (Abstract MP16-03).
