MP16-03: N-803 plus BCG Complete Response rate in NMIBC CIS subjects: BCG refractory, relapsed, checkpoint failure, and chemotherapy failure; updated results (QUILT 3.032)

Author Block

Patrick Soon-Shiong*, El Segundo, CA, Sandeep Reddy, Los Alamitos, CA, Karim Chamie, Los Angeles, CA

Introduction

Patients with 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. We 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.

Methods

All treated patients received intravesical N-803 plus BCG, consistent with the standard induction/maintenance treatment schedule. The primary endpoint for CIS is incidence of complete response (CR) of CIS at any time. The subset analyses were pre-planned per protocol.

Results

All CIS subjects received prior BCG, the median number of prior BCG doses received was 12.0 doses (range, 5 to 48 doses). The median time from last prior BCG dose to first documented CIS disease recurrence was 2.46 months (range, 0.7 to 11.1 months). Forty-eight (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). With regard to prior BCG therapy, seventy-four (74) subjects received = 12 prior BCG doses. In this group, 51 out of 74 had a CR, yielding a CR rate of 69% (57.1, 79.2), and 14/20 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). Thus, 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 Kaplan-Meier method, 61.3% of subjects had a duration of CR lasting >12 months and 53.2% had a duration of >24 months.

Conclusions

N-803 plus BCG results in a high CR rate in subjects who failed both BCG and other therapies, including additional BCG, chemotherapy and checkpoint inhibitors, with a median duration of response of >28 months.

Source Of Funding

ImmunityBio