Bladder Cancer

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 81,180 new cases and 17,100 deaths from bladder cancer in 2022. 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 this Phase 2/3 open-label multi-center trial of BCG-unresponsive high grade NMIBC CIS 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.

A data cutoff occurred in January 2022, which provided a median follow-up in Cohort A in excess of 24 months. Data presented at the ASCO® Genitourinary Cancers Symposium in February 2022 showed a complete response in 59 of 83 patients 71% CR rate (95% CI: 60.1, 80.5) and a median duration of CR of 24.1 months. In those patients who responded to the investigational therapeutic, the probability of avoiding both progression of bladder cancer and cystectomy at 24 months exceeded 90%. The combination of Anktiva and BCG had a well-tolerated profile with 0% treatment-related serious adverse events (SAEs), 0% immune-related AEs, and 100% bladder cancer-specific overall survival at 24 months.

QUILT 3.032 – BCG-Unresponsive Non-Muscle Invasive Bladder Cancer Papillary

In this Phase 2, open-label multi-center trial of BCG-unresponsive high grade NMIBC papillary patients (Cohort B), 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 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.

Data presented at the ASCO® Genitourinary Cancers Symposium in February 2022 showed a 12-month disease-free rate of 57% (95% CI: 44, 68) in the papillary Cohort B, in which 73 of 77 patients (95%) have not progressed to radical cystectomy after a median duration of follow-up of 20.7 months, and a 99% bladder cancer-specific survival through the January 2022 data cutoff.

QUILT 2.005 – BCG-Naïve

ImmunityBio is currently enrolling patients in a Phase 2b blinded, randomized, two-cohort, open-label, multi-center trial of intravesical Anktiva plus BCG 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 patients and 230 patients, respectively.

1. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2792453/
2. https://doi.org/10.1016/j.eururo.2018.09.028/