One such novel agent is Vesigenurtacel-L (HS-410), an allogenic cell line vaccine that induces the expression of heat shock protein gp96-Ig, promoting activation of highly selective CD8+ cytotoxic T cells. From a phase 2 trial of HS-140 and BCG in NMIBC, 1-year recurrence free survival for combined therapy was not significantly lower than in patients treated with BCG alone. However, response rates were superior to historic rates with BCG alone. As such, they proceeded to assess the influence of blue-light cystoscopy (BLC) on RFS.
In this series, 78 patients with intermediate (n=5) or high-risk (n=73) NMIBC - who were either BCG-naïve or recurrent - were randomized to either 6 weeks of low-dose HS-410, high-dose HS-410, or placebo therapy during their 6-week induction BCG. Maintenance therapy during the first year consisted of 3-weekly treatments (combination therapy) at the 3, 6, and 12-month mark. The primary endpoint was 1-year RFS, which was analyzed with respect to use of BLC on initial TURBT.
Of the 78 patients, 21 (26.9%) underwent BLC at initial TURBT. Patients undergoing BLC had a higher rate of CIS and were more likely to be pTis rather than pT1/Ta. Median follow-up was 14 (IQR 13-16) months, during which 21 patients recurred. The estimated 1-year RFS and 1-year DFS was 95% (95%CI 86-100%) in patients with BLC compared to 70% (95%CI 59-83%) in patients without BLC (p=0.047). On univariable logistic regression, the use of BLC was associated with a significant reduction in the odds of recurrence at 1 year (OR 0.12; 95%CI 0.01-0.95; p=0.04).
However, it is unclear what the role of HS-410 in this study was. It was primarily focused on evaluating the role of BLC at the time of initial TURBT on 1-year RFS, which has been previously established. The authors conclude that BLC seems to significantly reduce RFS at one year, which is already well studied independent of HS-410. However, they do note that patients in all combination arms performed better than historical data on BCG alone – which may have contributed to the lack of statistically significant difference between the HS-410 and placebo arms. Even patients without BLC showed RFS in excess of historical reported rates – possibly due to initial TURBT being performed at tertiary centers.
As such, it is hard to make any conclusions from the results of this study, especially as it pertains to HS-410.
Presented by: Andrew Zganjar, MD
Co-Authors: William Parker MD¹, Jeffery Holzbeierlein MD¹, Gary Steinberg MD², Neal Shore MD³, Lawrence Karsh MD⁴, James Bailen MD⁵, Trinity Bivalacqua MD, PhD⁶, Karim Chamie MD⁷, James Cochran MD⁸, Richard David MD⁹, Robert Grubb MD¹⁰, Wael Harb MD¹¹, Ashish Kamat MD¹², Vijay Kasturi MD¹³, Edouard Trabulsi MD¹⁴, William Walsh MD¹³, Michael Williams MD¹⁵, Frederick Wolk MD⁹, Michael Woods MD¹⁶, Melissa Price PhD¹⁷, Brandon Early MS¹⁸ and Taylor Schreiber MD, PhD¹⁸
Affiliation: ¹University of Kansas Medical Center, Kansas City, KS; ²University of Chicago Medical Center, Chicago IL; ³Carolina Urologic Research Center, Myrtle Beach, SC; ⁴The Urology Center of Colorado, Denver, CO; ⁵First Urology, Jeffersonville, IN; ⁶Johns Hopkins University, Baltimore, MD; ⁷University of California Los Angeles, Los Angeles, CA; ⁸Urology of North Texas, Dallas, TX; ⁹Skyline Urology, Torrance, CA; ¹⁰Washington University of St. Louis, St. Louis, MO; ¹¹Horizon Oncology, Lafayette, IN; ¹²MD Anderson Cancer Center, Houston, TX; ¹³University of Massachusetts Memorial Medical Center, Worcester MA; ¹⁴Thomas Jefferson University, Philadelphia, PA; ¹⁵Urology of Virginia, Virginia Beach, VA; ¹⁶University of North Carolina, Chapel Hill, NC; ¹⁷Taris Biomedical LLC, Lexington, MA; ¹⁸Heat Biologics Inc., Durham, NC
Written by: Thenappan Chandrasekar, MD, Clinical Fellow, University of Toronto, twitter: @tchandra_uromd at the 18th Annual Meeting of the Society of Urologic Oncology, November 20-December 1, 2017 – Washington, DC