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

abstract

  • 319 Background: 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. Trial ID NCT02010203. 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 further 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. Clinical trial information: NCT02010203.

authors

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

Publication Date

  • 2017

webpage

published in

Digital Object Identifier (DOI)

number of pages

  • 1

start page

  • 319

end page

  • 319

volume

  • 35

issue

  • 6_suppl