4 research outputs found
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Quality of life in QUILT 3.032 study: Patients with BCG-unresponsive non-muscle invasive bladder cancer (NMIBC) receiving IL-15RαFc superagonist N-803 plus BCG
495 Background: Patients (pts) with BCG-unresponsive NMIBC have limited treatment options and are at an increased risk for cystectomy. Nogapendekin alfa inbakicept (NAI, also known as N-803), is an interleukin-15 superagonist (IL-15RαFc), which synergizes with BCG to elicit innate immune memory resulting in durable complete responses (CRs) in this patient population. In an open-label, 3-cohort, multicenter Phase 2/3 study of intravesical BCG plus NAI in BCG-unresponsive high-grade NMIBC (QUILT 3.032; NCT03022825), pts with carcinoma in situ (CIS; Cohort A) have a CR rate of 71% (median duration 26.6 months), 89.2% cystectomy avoidance and 100% bladder cancer specific survival at 24 months. We submit here the first quality of life (QOL) data report in the same pts cohort. Methods: Cohort A: 86 pts (median age 73 years; 87% male) with histologically confirmed BCG-unresponsive CIS with or without Ta/T1 disease, treated with intravesical BCG 50 mg plus NAI 400 μg. Mean baseline ECOG score was 0.183, with 82% of pts having score = 0. QOL was measured by the EORTC QOL Questionnaire Core 30 (QLQ-C30) and QOL NIMBC-Specific 24 Questionnaire (QLQ-NMIBC24). Results: Multivariate analyses have shown no significant changes over time for any of the measured QOL domains. Mild worsening vs. baseline in feeling ill was reported by 6% and 3% of pts by week 27 and 52, while 4% and 6% reported improvement. By week 78 and 104, 7% and 9% of pts reported improvement vs. baseline in their wellbeing with the majority being stable (non-significant). No statistically significant variations were detected in the physical function (PF) score (baseline vs. week 27, 52, 78 and 104). Higher PF scores were observed in pts responding to the therapy vs. non-responders; however, baseline value of PF was also higher in responders vs. non-responders. In contrast to historical results of BCG alone, week 27 physical function scores were numerically higher than baseline, with a subsequent nadir at week 78 and recovery to baseline by week 104 (non-significant). Hospitalizations for any reason remained low (0% - 6% per assessments) during the study. Conclusions: QOL measurement supports good tolerability of the intravesical NAI plus BCG in BCG-unresponsive, high-grade NMIBC pts with CIS. These results further strengthen the evidence of a favorable benefit: risk ratio of this novel combination immunotherapy, in a challenging disease. Clinical trial information: NCT03022825
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Phase II/III clinical results of IL-15RαFc superagonist N-803 with BCG in BCG-unresponsive non-muscle invasive bladder cancer (NMIBC) carcinoma in situ (CIS) patients
510
Background: Patients with NMIBC CIS unresponsive to BCG have limited treatment options. N-803 (Anktiva) is a mutant IL-15-based immunostimulatory fusion protein complex (IL-15RαFc) that promotes proliferation and activation of natural killer (NK) cells and CD8+ T cells, but not regulatory T cells. Phase Ib data in BCG-naive patients with NMIBC demonstrate that intravesical administration of N-803 with BCG induced complete response in all patients, without recurrences for the study duration of 24 months. An open-label, 3 cohort multicenter phase II/III study (QUILT 3.032) of intravesical BCG plus N-803 in patients with BCG-unresponsive high-grade NMIBC (NCT03022825) was opened. We report here the interim analysis of Cohort A, BCG-unresponsive (CIS) [with or without Ta or T1 disease], as of December 2020 data cutoff. Methods: All treated patients received intravesical N-803 plus BCG, consistent with the standard induction/maintenance treatment schedule. The primary endpoint for Cohort A of this phase II/III study is incidence of complete response (CR) of CIS at any time. Results: To date, 80 patients have enrolled in cohort A of this phase II/III trial. Evaluable analysis at this time shows CR rate at any time of 72% (N=51/71); for patients achieving CR, the probability of maintaining a CR for 12 months is 59%, with a median duration of complete response of 19.2 (7.6, 26.4) months. Low-grade treatment related AEs include dysuria, hematuria, and pollakiurua (all 16%), urgency (14%), and bladder spasm (8%), all other AEs were seen at 6% or less. A total of 9 subjects experienced at least 1 treatment emergent SAE (Severe Adverse event), the SAE rate is 1% for any given AE. No treatment emergent SAE’s were considered treatment related. No immune related SAE’s have been seen. To date, 10/80 (12.5%) patients proceeded to cystectomy in this BCG unresponsive population. Conclusions:With a CR rate of 72%, N-803 has met its primary endpoint with 59% probability of CR patients maintaining CR for at least 12 months. With the observed strong efficacy and an SAE rate of 1%, N-803 represents a novel treatment option for BCG unresponsive CIS with a favorable benefit:risk ratio, in a therapeutically challenging disease. Clinical trial information: NCT03022825