Immune response results from vesigenurtacel-l (HS-410) in combination with BCG from a randomized phase 2 trial in patients with non-muscle invasive bladder cancer (NMIBC)

Vesigenurtacel-L (HS-410) is a vaccine comprised of an allogeneic cell line, selected for high expression from a series of bladder tumor antigens, and transfected with gp96-Ig. Cell-secreted gp96-Ig delivers these cell-derived antigens to a recipient's own antigen presenting cells, activating CD8+ cytotoxic T cells. Here we present the secondary immune outcomes from a randomized Phase 2 trial with HS-410 in combination with BCG in NMIBC.

Methods:
78 patients with intermediate- (n = 5) or high-risk (n = 73) NMIBC who are either BCG-naïve or recurrent, with or without carcinoma in situ (CIS), were enrolled 1:1:1 to one of two doses of HS-410 (either 10⁶ or 10⁷cells/dose) or placebo in combination with 6 weeks of induction BCG, followed by 6 more weeks of HS-410 in the induction phase. Maintenance treatment consisted of 3-weekly treatments at the following timepoints: 3 mo., 6 mo., 12 mo. Concurrently, 16 patients (1 int. risk, 15 high-risk) were enrolled in an open-label monotherapy HS-410 arm for patients who did not receive BCG. The primary endpoint was 1-year RFS. Secondary immune evaluations include ELISPOT, tumor IHC, tumor antigen profiling, flow cytometry, urine cytokine analysis, and T cell receptor sequencing.

Results:
HS-410 treatment was well tolerated; AE profiles were similar across the treatment arms. HS-410 antigen expression showed prominent overlap with patient tumors. IFNγ ELISPOT assay demonstrated a high baseline response to HS-410; responses to overlapping peptide pools of HS-410 derived antigens defined immune responders (doubling of IFNγ-secreting cells). IHC demonstrated that ~60% of NMIBC patient tumor biopsies were TIL negative at baseline (n = 84), but that only ~15% of tumor biopsies were TIL negative post treatment (n = 40). Thus, TIL status may be used to define a responder and non-responder population to HS-410.

Conclusions:
Vesigenurtacel-L is well-tolerated, and immunologic responses consistent with vaccine mechanism of action may correlate with efficacy and suggest future biomarkers. Vesigenurtacel-L warrants further investigation as a potential treatment for NMIBC.

Gary D. Steinberg, Neal D. Shore, Lawrence Ivan Karsh, James L. Bailen, Trinity J. Bivalacqua, Karim Chamie, James S. Cochran, Richard David, Robert L. Grubb, Wael A. Harb, Jeffrey M. Holzbeierlein, Ashish M. Kamat, Edouard John Trabulsi, William Vincent Walsh, Michael Brandon Williams, Fredrick Wolk, Michael Woods, Melissa Leigh Price, Brandon Early, Taylor Houghton Schreiber

DOI: 10.1200/JCO.2017.35.6_suppl.319 Journal of Clinical Oncology 35, no. 6_suppl (February 2017) 319-319.

Clinical trial information: NCT02010203

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