The standard of care for patients with Bacillus Calmette-Guérin (BCG)-unresponsive, high-risk non–muscle invasive bladder cancer is radical cystectomy. Novel therapies that allow patients to preserve their bladder are urgently needed. SWOG (formerly the Southwest Oncology Group), a member of the National Clinical Trials Network of the National Cancer Institute (NCI), recently launched the first federally funded immune checkpoint inhibitor trial for non–muscle invasive bladder cancer. This trial will accrue patients at cooperative-group and associated network institutions in both the United States and Canada.
S1605 is a phase II trial of atezolizumab (Tecentriq) in BCG-unresponsive, high-risk non–muscle invasive bladder cancer. It is sponsored by the NCI and conducted under NCI collaborative agreements with Genentech for atezolizumab. Results from this registration trial may be used to seek U.S. Food and Drug Administration approval for the use of atezolizumab in the treatment of these patients.
S1605 is a single-arm study enrolling patients who have persistent or recurrent high-grade Ta/T1 or carcinoma in situ after intravesical BCG treatment. Patients will be enrolled into predefined subgroups with Ta/T1 alone or with carcinoma in situ (with or without concomitant Ta/T1).
These patients will receive atezolizumab infusion every 3 weeks. They will have cytology and cystoscopy every 12 weeks to evaluate for response and event-free survival. An event in the context of this trial is defined as persistence of carcinoma in situ at week 25, recurrence of high-grade Ta/T1/carcinoma in situ, progression to muscle invasive bladder cancer, high-grade urothelial carcinoma of the upper tract or prostatic urethra, or evidence of metastatic disease.
All patients with carcinoma in situ at the time of registration will undergo a mandatory biopsy at 25 weeks. Patients who are responding and have no serious adverse effects from the medication will continue treatment for 1 year.
The goal of the trial is to accrue 148 patients within 3 years. The trial is designed with coprimary endpoints: (1) the rate of complete response at 25 weeks in patients with carcinoma in situ; and (2) event-free survival at 18 months in all patients (Ta/T1/carcinoma in situ). S1605 includes important translational medicine components focusing on predictive markers of response to atezolizumab. They will include programmed cell death ligand 1 (PD-L1) and CD8 expression by immunohistochemistry and tumor immune signatures by RNA sequencing.
“We will determine whether atezolizumab eliminates tumors within the bladder, keeps cancer from returning, and ultimately allows patient to keep their bladders,” said study Co-Chair Peter Black, MD, FRCSC, FACS, Associate Professor of Urology at the University of British Columbia, Vancouver. “We’re really excited to see whether this new immunotherapy can make a difference in this treatment-resistant type of bladder cancer. If it does, it might be a huge difference.”
The goal of [S1605] is to accrue 148 patients within 3 years. The trial is designed with coprimary endpoints: (1) the rate of complete response at 25 weeks in patients with carcinoma in situ; and (2) event-free survival at 18 months in all patients (Ta/T1/carcinoma in situ).— Parminder Singh, MD
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In addition to Dr. Black, the study’s other Co-Chair is Parminder Singh, MD, a medical oncologist at Mayo Clinic in Arizona. Seth P. Lerner, MD, FACS, is Senior Study Chair, providing guidance on the trial design and protocol. Dr. Lerner is the Beth and Dave Swalm Chair in Urologic Oncology at Baylor College of Medicine Medical Center, Co-Chair of the NCI’s Genitourinary Cancer Steering Committee, and Chair of the SWOG bladder cancer committee.
“Bladder cancer is a disease that disproportionately impacts older Americans, many of whom are unable to undergo the removal of their bladders. For patients who are unwilling [or unable] to have their bladders removed, the S1605 trial offers the possibility of a new treatment option, filling a significant gap in the treatment options available to the bladder cancer community. I will be excited to see results from this groundbreaking trial,” said Rick Bangs, SWOG’s patient advocate for bladder cancer and a bladder cancer (and radical cystectomy) survivor.
For more information, visit swog.org. ■
Disclosure: Drs. Black, Singh, Lerner, and Mr. Bangs reported no potential conflicts of interest.