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(UroToday.com) Most patients newly diagnosed with bladder cancer have invasive non-muscle disease (NMIBC). For patients with intermediate or high risk NMIBC and those with carcinoma in situ (CIS), adjuvant therapy with BCG is recommended by the guidelines based on proven benefit in disease recurrence. Although BCG is effective, many patients eventually develop a disease that does not respond to BCG. For many years, the options for these patients have been very limited. A new treatment option is N-803 (Anktiva), a complex of immunostimulatory fusion proteins based on mutant IL-15 (IL-15RαFc) that promotes the proliferation and activation of natural killer cells (NK) and CD8 + T cells, but not regulatory T cells.
Preliminary data from a phase Ib trial in BCG-naïve patients with NMIBC demonstrate that intravesical administration of N-803 with BCG induced a complete response without recurrence over 24 months of follow-up. Thus, the QUILT 3.032 study was designed as a 3-cohort, open-label, multicenter phase II / III study of intravesical BCG plus N-803 in patients with high-grade NMIBC unresponsive to BCG (NCT03022825). In a plenary summary presentation at the Rapid Summary Session: Urothelial Carcinoma and Rare Tumors at the 2021 ASCO GU Cancer Symposium, Dr Karim Chamie and colleagues report the interim results of this trial in Cohort A , with BCG-insensitive CIS [with or without Ta or T1 disease].
Among patients with BCG-insensitive CIS [with or without Ta or T1 disease], all patients in the cohort received intravesical N-803 plus BCG according to the standard induction / maintenance treatment schedule. For this analysis, the primary endpoint in this cohort (A) is the incidence of CIS complete response (CR) at any time.
As of the data cut-off date of December 2020, to date, 80 patients are enrolled in Cohort A. Enrolled patients generally correspond to a BCG-refractory NMIBC cohort with a mean age of 73 years, a preponderance of males (86 %), most of them white (90%), and generally good performance (ECOG PS = 0 to 82%). In addition, most patients had CIS at the time of the first recurrence (69%) while 21% had CIS and Ta disease and 9% had CIS and T1 disease. Patients were recruited at a median of 6.2 months from the last dose of BCG and 2.3 months from the first detected recurrence. In particular, the median time between the last dose of BCG and the first recurrence detected was 2.7 months.
Dr Chamie noted that this was a heavily pretreated cohort with a median of 5 prior TURBTs and a median of 16 prior instillations of BCG. All the patients had previously received BCG. In addition, 78% of patients received additional treatment beyond BCG comprising checkpoint inhibitors in 3%, chemotherapy in 59%, interferon in 13% and vicinium in 3%.
Treatment was generally well tolerated with low-grade treatment-related AEs including dysuria (18%), hematuria 915%) and pollakiuria (14%), urgency (8%), bladder spasm (5%), fatigue (8%), chills (6%) and pyrexia (5%). All other AEs were observed at 6% or less. Serious adverse events occurring during treatment were noted in 9 subjects with a rate of 1% for any given AE. Notably, none of these adverse effects were considered to be related to treatment and no serious AEs of immunological origin were noted. In addition, there was no treatment discontinuation or Grade 5 treatment-related event.
At this time point (with a median follow-up of 10.7 months), a complete response at all times was noted in 51 of 72 evaluable patients (72%). As a result, the primary endpoint was met. To date, 10/80 (12.5%) patients have undergone cystectomy in this BCG-insensitive population.
Among those who achieved CR, the likelihood of maintaining CR for 12 months was 56%, with a median duration of CR of 19.2 months (7.6 to not achieved).
In comparison with other agents in this pathological space, Dr. Chamie pointed out that these data appear to be favorable for N-803.
Thus, the authors conclude that, in this cohort of the QUILT 3.032 trial, treatment achieved the primary endpoint with a CR rate of 72% and a probability of 56% that patients with CR will maintain CR for at least 12 months. In addition, there were no serious treatment-related adverse events and this treatment was well tolerated. This represents a new therapeutic approach in this rapidly evolving disease space.
Presented by: Karim Chamie, MD, Associate Professor of Urology David Geffen School of Medicine at UCLA University of California, Los Angeles
Co-authors: Sam Chang, Mark L. Gonzalgo, Eugene V. Kramolowsky, Wade J. Sexton, Sandeep K. Reddy, Paul Bhar, Chad Garner, Patrick Soon-Shiong
Written by: Christopher JD Wallis, Urologic Oncology Researcher, Vanderbilt University Medical Center Twitter @WallisCJD at the ASCO 2021 Genitourinary Cancer Symposium (ASCO GU), February 11-13, 2021
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