The combination of the novel interleukin-15 superagonist N-803 (Anktiva) and Bacille Calmette-Guérin (BCG) met the primary end point of disease-free survival (DFS) in patients with BCG-unresponsive, high-grade non–muscle-invasive bladder cancer (NMIBC) and papillary disease, according to updated findings from the phase 2/3 QUILT-3.032 trial.1
The DFS rate was 57% at 12 months and 53% at 18 months. The median follow-up time overall was 17.3 months. The responses were durable, with the treatment enabling 85% of patients to avoid cystectomy.
The papillary group made up cohort B of the QUILT-3.032 trial. Previously reported findings showed that the primary end point was also met in cohort A, which enrolled patients with carcinoma in situ (CIS).
"Intravesical BCG has been the standard of care for more than 30 years for patients with noninvasive papillary tumors, yet, unfortunately some 40% of them don’t respond," Patrick Soon-Shiong, MD, founder and executive chairman and Global Chief Scientific and Medical Officer of ImmunityBio, the manufacturer of N-803, stated in a press release. "Anktiva has demonstrated strong disease control in CIS, and based on the latest data from our study, it is showing the same effect in papillary tumors. This gives us confidence in the potential for all BCG-unresponsive NMIBC patients to benefit from this combination therapeutic."
Overall, QUILT 3.032 is a multicenter, open-label, 3-cohort study. In cohorts A (CIS) and B (papillary) patients are treated with BCG plus N-803. Cohort C is enrolling patients with CIS and treating them with N-803 alone. While the primary end point of cohort B is DFS rate, the primary end point for cohorts A and C is the rate of complete response (CR).
At the time the results were reported, 73 patients had enrolled in cohort B. Previously reported results for cohort A included data for 81 patients. Results presented for cohort A during the 2021 American Urological Association Annual Meeting showed that BCG plus N-803 reached a CR rate of 72% and a 58.6% probability of maintaining a CR for at least 12 months.2 Additionally, at a median follow-up of 20.4 months, the median duration of CR was 19.9 months.
A combined safety analysis of cohorts A and B (n = 154) showed that there were no immune-related or treatment-related severe adverse events in any patients.
In December 2019, the FDA granted N-803 a Breakthrough Therapy Designation for use in combination with BCG in patients with BCG-unresponsive NMIBC and CIS.
ImmunityBio plans to share full efficacy and safety data for cohorts A and B at the ASCO GU Symposium in February 2022.
1. ImmunityBio Announces Primary Endpoint Met in a Second Indication in Bladder Cancer Trial with 57% Disease-Free Survival in Patients with BCG Unresponsive Papillary Disease. Published online October 19, 2021. Accessed October 20, 2021. https://yhoo.it/3pkHMwp.
2. Chamie K, Chang S, Gonzalgo M, et al. Phase 2/3 clinical results of IL-15RαFc superagonist N-803 with BCG in BCG-unresponsive non-muscle invasive bladder cancer (NMIBC) carcinoma in-situ (CIS) patients (cohort A). Presented at: 2021 American Urological Association Annual Meeting; September 10-13, 2021; virtual. Abstract PD09-05