This phase II trial studies how well TPIV100 and sargramostim work in treating patients with
HER2 positive, stage II-III breast cancer that has remained after chemotherapy and surgery.
It also studies why some HER2 positive breast cancer patients respond better to chemotherapy
in combination with trastuzumab and pertuzumab. TPIV100 is a type of vaccine made from HER2
peptide that may help the body build an effective immune response to kill tumor cells that
express HER2. Sargramostim increases the number of white blood cells in the body following
chemotherapy for certain types of cancer and is used to alert the immune system. It is not
yet known if TPIV100 and sargramostim will work better in treating patients with HER2
positive, stage II-III breast cancer.
I. To evaluate invasive disease free survival (iDFS) of multi-epitope HER2 vaccine versus
(vs.) placebo in combination with ado-trastuzumab emtansine (TTT-DM1) in patients with stage
II-III HER2 positive (+) breast cancer (BC) with residual disease post-neoadjuvant
II. To evaluate the safety of multi-epitope HER2 vaccine given concurrently with
ado-trastuzumab emtansine (T-DM1) maintenance therapy.
I. To evaluate immunogenicity of multi-epitope HER2 vaccine in combination with T-DM1
II. To evaluate the immune-related tissue and blood biomarkers for complete pathological
response in patients with stage II-III HER2+ BC receiving neoadjuvant chemotherapy.
CORRELATIVE RESEARCH OBJECTIVES:
I. To determine host immune factors which are critical to prevent disease recurrence in HER2+
Ia. To determine if the development of T cell immunity, as assessed by IFN-gamma
enzyme-linked immunospot (ELISpot), to HER2 correlates with improved iDFS.
Ib. To determine the distribution of the helper T cell response among helper T cell
Ic. To determine if augmenting CD4 helper T cell immunity augments HER2-specific antibody
immunity induced by trastuzumab.
Id. To determine if human leukocyte antigen (HLA) genotypes are associated with antibody
responses before and after neoadjuvant therapy and vaccination.
Ie. To determine gene expression levels in tumors from patients who did not achieve complete
pathological response (pCR) that are associated with recurrence.
II. To determine tumor intrinsic genotyping and phenotyping features associated with
therapeutic failure to HER2 immune-based approaches.
IIa. To determine whether HER2 monoclonal antibody therapy induces HER2 loss and modulation
of HER2-specific adaptive immune responses.
IIb. To determine loss-of-function mutations in breast tumor that associate with lack of pCR
and lack of immune response to HER2+ neoadjuvant treatment.
pCR AFTER NEOADJUVANT CHEMOTHERAPY AND SURGERY: Patients receive standard of care maintenance
therapy with trastuzumab and pertuzumab for 1 year in the absence of disease progression or
NO pCR AFTER NEOADJUVANT CHEMOTHERAPY AND SURGERY: Patients are randomized to 1 of 2 arms.
ARM I: Patients receive standard of care maintenance therapy with trastuzumab emtansine and
receive TPIV100 intradermally (ID) and sargramostim ID on day 1. Treatment repeats every 21
days for up to 6 cycles in the absence of disease progression or unacceptable toxicity.
Patients then receive two additional booster injections of TPIV100 ID and sargramostim ID at
3 and 12 months after completion of trastuzumab emtansine maintenance therapy.
ARM II: Patients receive standard of care maintenance therapy with trastuzumab emtansine and
receive placebo ID and sargramostim ID on day 1. Treatment repeats every 21 days for up to 6
cycles in the absence of disease progression or unacceptable toxicity. Patients then receive
two additional booster injections of placebo ID and sargramostim ID at 3 and 12 months after
completion of trastuzumab emtansine maintenance therapy.
After completion of study treatment, patients with pCR are followed up at 30 days and 24
months. Patients with no pCR followed up at 30 days and at 3, 4, 12, 13, and 24 months. All
patients are then followed up every 6 months for up to 5 years.
Stage III Breast Cancer AJCC v7,
Stage IIIA Breast Cancer AJCC v7,
Stage IIIB Breast Cancer AJCC v7,
Stage IIIC Breast Cancer AJCC v7,
Adenocarcinoma of the Breast,
Stage II Breast Cancer AJCC v6 and v7,
Stage IIA Breast Cancer AJCC v6 and v7,
Stage IIB Breast Cancer AJCC v6 and v7
If you are confirmed eligible after full screening, you will be required to understand and sign the informed consent if you decide to enroll in the study. Once enrolled you may be asked to make scheduled visits over a period of time.
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