An Urgent Need to Treat Bladder Cancer and Prevent Radical Cystectomy
In the U.S., bladder cancer is the fourth most commonly-diagnosed solid malignancy in men and twelfth in women. The American Cancer Society estimates there will be 82,290 new cases and 16,710 deaths from bladder cancer in 2023. There is an urgent, unmet need to treat NMIBC and avoid radical cystectomy (removal) of the bladder in an attempt to control the disease.
While BCG is an effective treatment for many patients, it doesn’t work for an estimated 40% of NMIBC cases.1 That can mean a lifetime of invasive examinations followed by immediate treatment for a recurrence. The recurrence of NMIBC diminishes quality of life and poses a significant financial burden for most patients – and 30% of patients with a recurrence will decline and succumb over the course of 15 years. For another 50% of patients, controlling the disease will require them to undergo radical cystectomy of the bladder.2 The FDA has issued guidance for the design of studies for the development of NMIBC treatments that includes the goal of avoiding this drastic surgery.
Bladder Cancer Clinical Trials
QUILT 3.032 – BCG-Unresponsive Non-Muscle Invasive Bladder Cancer Carcinoma In Situ (CIS)
In our Phase 2/3 open-label multi-center trial of BCG-unresponsive high grade NMIBC patients, the patients are receiving BCG plus Anktiva weekly for six consecutive weeks during induction. The patients also receive additional treatment including three weekly maintenance instillations every three months for up to 12 months and then at month 18.
The primary endpoint of the BCG-unresponsive NMIBC CIS trial is a CR rate at any time equal to or greater than 30% and the lower bound of the 95% confidence interval must be greater than or equal to 20% for success. Complete response, or the disappearance of measurable disease in response to treatment, is evaluated at three months or six months following initial administration of BCG plus Anktiva (and every three months thereafter until 24 months). This endpoint would be achieved once at least 24 of the 80 patients in the trial achieve complete response.
A data cutoff occurred in January 2022, which provided a median follow-up in Cohort A of approximately 24 months. Data as published in NEJM Evidence in November 2022 showed a complete response in 58 of 82 patients with a 71% CR rate (95% CI: 59.6, 80.3) and a median duration of CR of 26.6 months (95% CI: 9.9, [upper bound not reached]). At 24 months in patients with complete response, the probability of avoiding cystectomy and disease-specific survival was 91.4% and 100%, respectively. Also at 24 months in all patients in Cohort A, the probability of avoiding cystectomy and of disease-specific survival was 84.1% and 100%, respectively.
In May 2022, we announced the submission of a BLA to the FDA for our product candidate, Anktiva in combination with BCG for the treatment of patients with BCG-unresponsive NMIBC with CIS with or without Ta or T1 disease. In July 2022, we announced that the FDA had accepted our BLA for review and set a target PDUFA action date of May 23, 2023.
QUILT 3.032 – BCG-Unresponsive Non-Muscle Invasive Bladder Cancer Papillary
In our Phase 2, open-label multi-center trial of BCG-unresponsive high grade NMIBC papillary patients (Cohort B), the patients are receiving BCG plus N-803 weekly for six consecutive weeks during induction. The patients also receive additional treatment including three weekly maintenance instillations every three months for up to 12 months and then every nine months for up to 24 months. The primary endpoint of the trial is a 12-month disease free rate greater than or equal to 30% and the lower bound of the 95% confidence interval must be greater than or equal to 20% for success. To meet the primary endpoint, 24 out of 80 patients must be disease free at 12 months.
A data cutoff occurred in January 2022, which provided a median follow-up in Cohort B of approximately 21 months. Data as published in NEJM Evidence in November 2022 showed a 12-month disease-free survival rate of 55% (95% CI: 42.0, 66.8), with median disease-free survival of 19.3 months (95% CI: 7.4, [upper bound not reached]). At the cutoff date 67 of 72 patients, 93.1%, had not progressed to radical cystectomy and the 24-month disease-free survival rate was 97.7%.
QUILT 2.005 – BCG-Naïve
N-803 has been awarded Fast Track designation by the FDA for the treatment of BCG-naïve NMIBC CIS. We are currently enrolling patients in our Phase 2b blinded, randomized, two-cohort, open-label, multi-center trial of intravesical BCG plus Anktiva versus BCG alone, in BCG naïve patients with high-grade NMIBC CIS (Cohort A) and NMIBC papillary (Cohort B). Planned enrollment for Cohort A (CIS) and Cohort B (papillary) is 366 and 230 patients, respectively.
The data suggest that a high percentage of patients who respond within the first three months to treatment will maintain that complete response for 18 months and possibly beyond. But most importantly, 85% of the patients in the cohort avoided a cystectomy.