PMID- 37259799
OWN - NLM
STAT- MEDLINE
DCOM- 20230602
LR  - 20240302
IS  - 1940-6215 (Electronic)
IS  - 1940-6207 (Print)
IS  - 1940-6215 (Linking)
VI  - 16
IP  - 6
DP  - 2023 Jun 1
TI  - Phase II Trial of Nelipepimut-S Peptide Vaccine in Women with Ductal Carcinoma In 
      Situ.
PG  - 333-341
LID - 10.1158/1940-6207.CAPR-22-0388 [doi]
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 = 9) or GM-CSF alone (n = 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 
      post-operation. The increase was numerically greater in the NPS+GM-CSF arm, but 
      the difference was not statistically significant. NPS+GM-CSF is safe and 
      well-tolerated when given preoperatively to patients with DCIS. In patients with 
      HLA-A2-positive DCIS, two inoculations with NPS+GM-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.
CI  - (c)2023 American Association for Cancer Research.
FAU - O'Shea, Anne E
AU  - O'Shea AE
AUID- ORCID: 0000-0003-0785-8563
AD  - Department of Surgery, Brooke Army Medical Center, Ft. Sam Houston, Texas.
FAU - Clifton, Guy T
AU  - Clifton GT
AUID- ORCID: 0000-0001-5962-3876
AD  - Department of Surgery, Brooke Army Medical Center, Ft. Sam Houston, Texas.
FAU - Qiao, Na
AU  - Qiao N
AUID- ORCID: 0009-0009-1912-4832
AD  - Department of Breast Surgical Oncology, The University of Texas MD Anderson 
      Cancer Center, Houston, Texas.
FAU - Heckman-Stoddard, Brandy M
AU  - Heckman-Stoddard BM
AUID- ORCID: 0000-0003-1686-7154
AD  - Division of Cancer Prevention, National Cancer Institute, Bethesda, Maryland.
FAU - Wojtowicz, Malgorzata
AU  - Wojtowicz M
AUID- ORCID: 0000-0001-9630-7530
AD  - Division of Cancer Prevention, National Cancer Institute, Bethesda, Maryland.
FAU - Dimond, Eileen
AU  - Dimond E
AUID- ORCID: 0000-0001-7628-1783
AD  - Division of Cancer Prevention, National Cancer Institute, Bethesda, Maryland.
FAU - Bedrosian, Isabelle
AU  - Bedrosian I
AUID- ORCID: 0000-0002-8775-8361
AD  - Department of Breast Surgical Oncology, The University of Texas MD Anderson 
      Cancer Center, Houston, Texas.
FAU - Weber, Diane
AU  - Weber D
AUID- ORCID: 0000-0001-9976-3451
AD  - Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer 
      Center, Houston, Texas.
FAU - Garber, Judy E
AU  - Garber JE
AUID- ORCID: 0000-0001-9449-3982
AD  - Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, 
      Massachusetts.
AD  - Breast Oncology Program, Dana-Farber Brigham Cancer Center, Boston, 
      Massachusetts.
AD  - Center for Cancer Genetics and Prevention, Dana-Farber Cancer Institute, Boston, 
      Massachusetts.
AD  - Harvard Medical School, Boston, Massachusetts.
FAU - Husband, Alexander
AU  - Husband A
AUID- ORCID: 0009-0000-6033-529X
AD  - Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, 
      Massachusetts.
AD  - Center for Cancer Genetics and Prevention, Dana-Farber Cancer Institute, Boston, 
      Massachusetts.
FAU - Pastorello, Ricardo
AU  - Pastorello R
AUID- ORCID: 0000-0002-0124-2437
AD  - Breast Oncology Program, Dana-Farber Brigham Cancer Center, Boston, 
      Massachusetts.
AD  - Division of Breast Surgery, Department of Surgery, Brigham and Women's Hospital, 
      Boston, Massachusetts.
FAU - Lee, J Jack
AU  - Lee JJ
AUID- ORCID: 0000-0001-5469-9214
AD  - Department of Biostatistics, The University of Texas MD Anderson Cancer Center, 
      Houston, Texas.
FAU - Hernandez, Mike
AU  - Hernandez M
AUID- ORCID: 0000-0002-5074-5460
AD  - Department of Biostatistics, The University of Texas MD Anderson Cancer Center, 
      Houston, Texas.
FAU - Liu, Diane D
AU  - Liu DD
AUID- ORCID: 0000-0003-3301-0259
AD  - Department of Biostatistics, The University of Texas MD Anderson Cancer Center, 
      Houston, Texas.
FAU - Vornik, Lana A
AU  - Vornik LA
AUID- ORCID: 0000-0002-1812-0305
AD  - Department of Clinical Cancer Prevention, The University of Texas MD Anderson 
      Cancer Center, Houston, Texas.
FAU - Brown, Powel H
AU  - Brown PH
AUID- ORCID: 0000-0002-3398-163X
AD  - Department of Clinical Cancer Prevention, The University of Texas MD Anderson 
      Cancer Center, Houston, Texas.
FAU - Alatrash, Gheath
AU  - Alatrash G
AUID- ORCID: 0000-0002-7648-4377
AD  - Department of Stem Cell Transplant and Cellular Therapy, The University of Texas 
      MD Anderson Cancer Center, Houston, Texas.
FAU - Peoples, George E
AU  - Peoples GE
AUID- ORCID: 0000-0001-7118-8205
AD  - Cancer Vaccine Development Program, San Antonio, Texas.
FAU - Mittendorf, Elizabeth A
AU  - Mittendorf EA
AUID- ORCID: 0000-0002-9762-8536
AD  - Breast Oncology Program, Dana-Farber Brigham Cancer Center, Boston, 
      Massachusetts.
AD  - Harvard Medical School, Boston, Massachusetts.
AD  - Division of Breast Surgery, Department of Surgery, Brigham and Women's Hospital, 
      Boston, Massachusetts.
LA  - eng
GR  - HHSN261201200034C/CP/NCI NIH HHS/United States
GR  - N01CN35159/CA/NCI NIH HHS/United States
GR  - UG1 CA242609/CA/NCI NIH HHS/United States
PT  - Clinical Trial, Phase II
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Cancer Prev Res (Phila)
JT  - Cancer prevention research (Philadelphia, Pa.)
JID - 101479409
RN  - 83869-56-1 (Granulocyte-Macrophage Colony-Stimulating Factor)
RN  - 0 (HLA-A2 Antigen)
RN  - 0 (Peptide Fragments)
RN  - 0 (Vaccines, Subunit)
RN  - 0 (Cancer Vaccines)
SB  - IM
MH  - Humans
MH  - Female
MH  - Granulocyte-Macrophage Colony-Stimulating Factor
MH  - *Carcinoma, Intraductal, Noninfiltrating/surgery
MH  - HLA-A2 Antigen
MH  - Neoplasm Recurrence, Local/pathology
MH  - Peptide Fragments
MH  - Vaccines, Subunit/adverse effects
MH  - *Cancer Vaccines/adverse effects
PMC - PMC10903526
MID - NIHMS1897631
COIS- Dr. Peoples has a patent to Nelipepimut-S issued and reports grants from Sellas 
      Life Sciences during conduct of the study. Dr. Mittendorf reports compensated 
      participation on the following scientific advisory boards: Merck, Genomic Health, 
      and Roche/Genetech. Dr. Mittendorf also receives trial support to institution 
      (DFCI) from Roche/Genetech through a SU2C grant.
EDAT- 2023/06/01 06:42
MHDA- 2023/06/02 06:43
PMCR- 2024/02/29
CRDT- 2023/06/01 04:23
PHST- 2022/08/29 00:00 [received]
PHST- 2023/01/31 00:00 [revised]
PHST- 2023/04/24 00:00 [accepted]
PHST- 2023/06/02 06:43 [medline]
PHST- 2023/06/01 06:42 [pubmed]
PHST- 2023/06/01 04:23 [entrez]
PHST- 2024/02/29 00:00 [pmc-release]
AID - 726436 [pii]
AID - 10.1158/1940-6207.CAPR-22-0388 [doi]
PST - ppublish
SO  - Cancer Prev Res (Phila). 2023 Jun 1;16(6):333-341. doi: 
      10.1158/1940-6207.CAPR-22-0388.