TY - JOUR
T1 - Phase II Trial of Nelipepimut-S Peptide Vaccine in Women with Ductal Carcinoma In Situ
AU - O’Shea, Anne E.
AU - Clifton, Guy T.
AU - Qiao, Na
AU - Heckman-Stoddard, Brandy M.
AU - Wojtowicz, Malgorzata
AU - Dimond, Eileen
AU - Bedrosian, Isabelle
AU - Weber, Diane
AU - Garber, Judy E.
AU - Husband, Alexander
AU - Pastorello, Ricardo
AU - Lee, J. Jack
AU - Hernandez, Mike
AU - Liu, Diane D.
AU - Vornik, Lana A.
AU - Brown, Powel H.
AU - Alatrash, Gheath
AU - Peoples, George E.
AU - Mittendorf, Elizabeth A.
N1 - Publisher Copyright:
© 2023 American Association for Cancer Research.
PY - 2023/6/1
Y1 - 2023/6/1
N2 - NeuVax is a vaccine comprised of the HER2-derived MHC class I peptide E75 (nelipepimut-S, NPS) combined with GM-CSF. We completed a randomized trial of preoperative vaccination with NeuVax versus GM-CSF alone in patients with ductal carcinoma in situ (DCIS). The primary objective was to evaluate for NPS-specific cytotoxic T lymphocyte (CTL) responses. Patients with human leukocyte antigen (HLA)-A2-positive DCIS were enrolled and randomized 2:1 to NeuVax versus GM-CSF alone and received two inoculations prior to surgery. The number of NPS-specific CTL was measured pre-vaccination, at surgery, and 1 and 3 to 6 months post-operation by dextramer assay. Differences in CTL responses between groups and between pre-vaccination and 1-month post-operation were analyzed using a two-sample t test or Wilcoxon rank sum test. The incidence and severity of adverse events were compared between groups. Overall, 45 patients were registered; 20 patients were HLA-A2 negative, 7 declined participation, 1 withdrew, and 4 failed screening for other reasons. The remaining 13 were randomized to NeuVax (n ¼ 9) or GM-CSF alone (n ¼ 4). Vaccination was well-tolerated with similar treatment-related toxicity between groups with the majority (>89%) of adverse events being grade 1. The percentage of NPS-specific CTLs increased in both arms between baseline (pre-vaccination) and 1-month postoperation. The increase was numerically greater in the NPSþGM-CSF arm, but the difference was not statistically significant. NPSþGM-CSF is safe and well-tolerated when given preoperatively to patients with DCIS. In patients with HLA-A2-positive DCIS, two inoculations with NPSþGM-CSF can induce in vivo immunity and a continued antigen-specific T-cell response 1-month postsurgery. Prevention Relevance: This trial showed that vaccination of patients with HLA-A2-positive DCIS with NeuVax in the preoperative setting can induce a sustained antigen-specific T-cell response. This provides proof of principle that vaccination in the preoperative or adjuvant setting may stimulate an adaptive immune response that could potentially prevent disease recurrence.
AB - NeuVax is a vaccine comprised of the HER2-derived MHC class I peptide E75 (nelipepimut-S, NPS) combined with GM-CSF. We completed a randomized trial of preoperative vaccination with NeuVax versus GM-CSF alone in patients with ductal carcinoma in situ (DCIS). The primary objective was to evaluate for NPS-specific cytotoxic T lymphocyte (CTL) responses. Patients with human leukocyte antigen (HLA)-A2-positive DCIS were enrolled and randomized 2:1 to NeuVax versus GM-CSF alone and received two inoculations prior to surgery. The number of NPS-specific CTL was measured pre-vaccination, at surgery, and 1 and 3 to 6 months post-operation by dextramer assay. Differences in CTL responses between groups and between pre-vaccination and 1-month post-operation were analyzed using a two-sample t test or Wilcoxon rank sum test. The incidence and severity of adverse events were compared between groups. Overall, 45 patients were registered; 20 patients were HLA-A2 negative, 7 declined participation, 1 withdrew, and 4 failed screening for other reasons. The remaining 13 were randomized to NeuVax (n ¼ 9) or GM-CSF alone (n ¼ 4). Vaccination was well-tolerated with similar treatment-related toxicity between groups with the majority (>89%) of adverse events being grade 1. The percentage of NPS-specific CTLs increased in both arms between baseline (pre-vaccination) and 1-month postoperation. The increase was numerically greater in the NPSþGM-CSF arm, but the difference was not statistically significant. NPSþGM-CSF is safe and well-tolerated when given preoperatively to patients with DCIS. In patients with HLA-A2-positive DCIS, two inoculations with NPSþGM-CSF can induce in vivo immunity and a continued antigen-specific T-cell response 1-month postsurgery. Prevention Relevance: This trial showed that vaccination of patients with HLA-A2-positive DCIS with NeuVax in the preoperative setting can induce a sustained antigen-specific T-cell response. This provides proof of principle that vaccination in the preoperative or adjuvant setting may stimulate an adaptive immune response that could potentially prevent disease recurrence.
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UR - http://www.scopus.com/inward/citedby.url?scp=85160810192&partnerID=8YFLogxK
U2 - 10.1158/1940-6207.CAPR-22-0388
DO - 10.1158/1940-6207.CAPR-22-0388
M3 - Article
C2 - 37259799
AN - SCOPUS:85160810192
SN - 1940-6207
VL - 16
SP - 333
EP - 342
JO - Cancer Prevention Research
JF - Cancer Prevention Research
IS - 6
ER -