TPIV100 and Sargramostim for the Treatment of HER2 Positive, Stage II-III Breast Cancer in Patients With Residual Disease After Chemotherapy and Surgery

Stage IIIC Breast Cancer AJCC v7 Clinical Trial

Official title:

Phase II Trial to Evaluate Immune-Related Biomarkers for Pathological Response in Stage II-III HER2-Positive Breast Cancer Receiving Neoadjuvant Chemotherapy With Subsequent Randomization to Multi-Epitope HER2 Vaccine vs. Placebo in Patients With Residual Disease Post-Neoadjuvant Chemotherapy

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04197687
• Other study ID #: MC1835-ACCRU-BR-1701
• Secondary ID: NCI-2019-08038MC
• Status: Recruiting
• Phase: Phase 2
• Start date: February 20, 2020
• Est. completion date: January 15, 2025

Study information

• Verified date: May 2023
• Source: Academic and Community Cancer Research United
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This phase II trial studies how well TPIV100 and sargramostim work in treating patients with HER2 positive, stage II-III breast cancer that has residual disease after chemotherapy prior to 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.

Description:

PRIMARY OBJECTIVES:

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 chemotherapy.

II. To evaluate the safety of multi-epitope HER2 vaccine given concurrently with ado-trastuzumab emtansine (T-DM1) maintenance therapy.

SECONDARY OBJECTIVES:

I. To evaluate immunogenicity of multi-epitope HER2 vaccine in combination with T-DM1 maintenance therapy.

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+ BC patients.

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 differentiation states.

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.

OUTLINE:

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 unacceptable toxicity.

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 2: Patients receive standard of care maintenance therapy with trastuzumab emtansine and receive placebo 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 placebo ID and sargramostim ID at 3 and 12 months after completion of trastuzumab emtansine maintenance therapy.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 480
• Est. completion date: January 15, 2025
• Est. primary completion date: January 15, 2025
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• PRE-REGISTRATION FOR ALL PATIENTS (INCLUDE SAFETY LEAD-IN): Histologically confirmed adenocarcinoma of the breast stage >= T2 OR >= N1 based on the 7th edition of tumor, node, metastases (TNM) staging system from the American Joint Committee on Cancer

• PRE-REGISTRATION FOR ALL PATIENTS (INCLUDE SAFETY LEAD-IN): Any estrogen receptor (ER) or progesterone receptor (PR) but HER2 positive defined as 3+ staining intensity (on a scale of 0 to 3) by means of immunohistochemistry (IHC) analysis OR gene amplification on fluorescence in situ hybridization (FISH) ratio >= 2.0

• PRE-REGISTRATION FOR ALL PATIENTS (INCLUDE SAFETY LEAD-IN): Willingness to provide adequate pretreatment biopsy sample

• NOTE: Adequate tissue samples defined as core needle biopsy or incisional biopsy or excisional samples that can provide >= 3 core needle biopsies with at least 14 gauge (G) needle with 12 unstained sections of 5 micron thickness. Fine needle aspiration (FNA) sample alone is not sufficient

• NOTE: Patients without adequate pretreatment biopsy samples must be agreeable to have an additional research biopsy prior to neoadjuvant therapy

• PRE-REGISTRATION FOR ALL PATIENTS (INCLUDE SAFETY LEAD-IN): Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1, 2

• PRE-REGISTRATION FOR ALL PATIENTS (INCLUDE SAFETY LEAD-IN): Willing to employ adequate contraception from the time of pre-registration through 6 months after the final vaccine cycle

• PRE-REGISTRATION FOR ALL PATIENTS (INCLUDE SAFETY LEAD-IN): Willing to receive a tetanus vaccination if subject has not had one =< 1 year prior to pre-registration

• PRE-REGISTRATION FOR ALL PATIENTS (INCLUDE SAFETY LEAD-IN): Provide written informed consent

• PRE-REGISTRATION FOR ALL PATIENTS (INCLUDE SAFETY LEAD-IN): Willing to return to enrolling institution for follow-up (during the Active Monitoring Phase of the study)

• PRE-REGISTRATION FOR ALL PATIENTS (INCLUDE SAFETY LEAD-IN): Willing to provide mandatory tissue and blood samples for correlative research purposes

• PRE-REGISTRATION FOR ALL PATIENTS (INCLUDE SAFETY LEAD-IN): Negative pregnancy test done =< 7 days prior to pre-registration, for persons of childbearing potential only

• NOTE: If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required

• REGISTRATION (SAFETY LEAD-IN): Absolute neutrophil count (ANC) >= 1500/mm^3 (obtained =< 28 days prior to registration)

• REGISTRATION (SAFETY LEAD-IN): Platelet count >= 75,000/mm^3 (obtained =< 28 days prior to registration)

• REGISTRATION (SAFETY LEAD-IN): Hemoglobin >= 9.0 g/dL (obtained =< 28 days prior to registration)

• REGISTRATION (SAFETY LEAD-IN): Direct bilirubin < 1.5 x upper limit of normal (ULN) (obtained =< 28 days prior to registration)

• REGISTRATION (SAFETY LEAD-IN): Aspartate transaminase (AST) =< 3 x ULN (obtained =< 28 days prior to registration)

• REGISTRATION (SAFETY LEAD-IN): Creatinine =< 2 x ULN (obtained =< 28 days prior to registration)

• REGISTRATION (SAFETY LEAD-IN): Prothrombin time (PT)/international normalized ratio (INR)/ partial thromboplastin time (PTT) =< 1.5 x ULN OR if patient is receiving anticoagulant therapy and PT or PTT is within therapeutic range of intended use of coagulant (obtained =< 28 days prior to registration)

• REGISTRATION (SAFETY LEAD-IN): Completed planned curative breast surgeries (not including any future breast reconstructive surgery) and any radiation therapy >= 30 days prior to registration

• REGISTRATION (SAFETY LEAD-IN): Completed last cycle of chemotherapy >= 90 days prior to registration

• NOTE: Prior to registration, patients must not receive > 8 cycles of TDM-1 maintenance therapy after surgery

• REGISTRATION (SAFETY LEAD-IN): Any residual disease after trastuzumab +/- pertuzumab based neoadjuvant chemotherapy warranted T-DM1 as per treating physician

• REGISTRATION (SAFETY LEAD-IN): Adequate tissue specimens from both pre-treatment biopsy and surgery must be submitted. Adequate tissue samples defined as core needle biopsy or incisional biopsy or excisional samples that can provide >= 3 core needle biopsies with at least 14G needle with 12 unstained sections of 5 micron thickness

• NOTE: Fine needle aspiration (FNA) sample alone is not sufficient

• REGISTRATION (SAFETY LEAD-IN): Negative pregnancy test done =< 7 days prior to registration, for persons of childbearing potential only

• NOTE: If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required

• REGISTRATION (SAFETY LEAD-IN): ECOG performance status (PS) 0, 1, 2

• REGISTRATION (SAFETY LEAD-IN): Willing to employ adequate contraception from the time of registration through 6 months after the final vaccine cycle

• REGISTRATION - FOR PATIENTS WITH NO RESIDUAL DISEASE (pCR) - (PHASE II): ECOG performance status (PS) 0, 1, 2

• REGISTRATION - FOR PATIENTS WITH NO RESIDUAL DISEASE (pCR) - (PHASE II): Absolute neutrophil count (ANC) >= 1500/mm^3 (obtained =< 28 days prior to registration)

• REGISTRATION - FOR PATIENTS WITH NO RESIDUAL DISEASE (pCR) - (PHASE II): Platelet count >= 75,000/mm^3 (obtained =< 28 days prior to registration)

• REGISTRATION - FOR PATIENTS WITH NO RESIDUAL DISEASE (pCR) - (PHASE II): Hemoglobin >= 9.0 g/dL (obtained =< 28 days prior to registration)

• REGISTRATION - FOR PATIENTS WITH NO RESIDUAL DISEASE (pCR) - (PHASE II): Direct bilirubin < 1.5 x upper limit of normal (ULN) (obtained =< 28 days prior to registration)

• REGISTRATION - FOR PATIENTS WITH NO RESIDUAL DISEASE (pCR) - (PHASE II): Aspartate transaminase (AST) =< 3 x ULN (obtained =< 28 days prior to registration)

• REGISTRATION - FOR PATIENTS WITH NO RESIDUAL DISEASE (pCR) - (PHASE II): Calculated serum creatinine clearance of >= 50 mL/minute (min.) (obtained =< 28 days prior to registration)

• REGISTRATION - FOR PATIENTS WITH NO RESIDUAL DISEASE (pCR) - (PHASE II): PT/INR/PTT =< 1.5 x ULN OR if patient is receiving anticoagulant therapy and PT or PTT is within therapeutic range of intended use of coagulants (obtained =< 28 days prior to registration)

• REGISTRATION - FOR PATIENTS WITH NO RESIDUAL DISEASE (pCR) - (PHASE II): Negative pregnancy test done =< 7 days prior to registration, for person of childbearing potential

• NOTE: If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required

• RANDOMIZATION - PATIENTS WITH RESIDUAL DISEASE POST NEOADJUVANT TRATUZUMAB +/- PERTUZUMAB BASED CHEMOTHERAPY (NO pCR) - (PHASE II): Absolute neutrophil count (ANC) >= 1500/mm^3 (obtained =< 28 days prior to randomization)

• RANDOMIZATION - PATIENTS WITH RESIDUAL DISEASE POST NEOADJUVANT TRATUZUMAB +/- PERTUZUMAB BASED CHEMOTHERAPY (NO pCR) - (PHASE II): Platelet count >= 75,000/mm^3 (obtained =< 28 days prior to randomization)

• RANDOMIZATION - PATIENTS WITH RESIDUAL DISEASE POST NEOADJUVANT TRATUZUMAB +/- PERTUZUMAB BASED CHEMOTHERAPY (NO pCR) - (PHASE II): Hemoglobin >= 9.0 g/dL (obtained =< 28 days prior to randomization)

• RANDOMIZATION - PATIENTS WITH RESIDUAL DISEASE POST NEOADJUVANT TRATUZUMAB +/- PERTUZUMAB BASED CHEMOTHERAPY (NO pCR) - (PHASE II): Direct bilirubin < 1.5 x upper limit of normal (ULN) (obtained =< 28 days prior to randomization)

• RANDOMIZATION - PATIENTS WITH RESIDUAL DISEASE POST NEOADJUVANT TRATUZUMAB +/- PERTUZUMAB BASED CHEMOTHERAPY (NO pCR) - (PHASE II): Aspartate transaminase (AST) =< 3 x ULN (obtained =< 28 days prior to randomization)

• RANDOMIZATION - PATIENTS WITH RESIDUAL DISEASE POST NEOADJUVANT TRATUZUMAB +/- PERTUZUMAB BASED CHEMOTHERAPY (NO pCR) - (PHASE II): Creatinine =< 2 x ULN (obtained =< 28 days prior to randomization)

• RANDOMIZATION - PATIENTS WITH RESIDUAL DISEASE POST NEOADJUVANT TRATUZUMAB +/- PERTUZUMAB BASED CHEMOTHERAPY (NO pCR) - (PHASE II): PT/INR/PTT =< 1.5 x ULN OR if patient is receiving anticoagulant therapy and PT or PTT is within therapeutic range of intended use of coagulant (obtained =< 28 days prior to randomization)

• RANDOMIZATION - PATIENTS WITH RESIDUAL DISEASE POST NEOADJUVANT TRATUZUMAB +/- PERTUZUMAB BASED CHEMOTHERAPY (NO pCR) - (PHASE II): Completed last cycle of chemotherapy >= 90 days prior to randomization

• NOTE: Prior to randomization, patients must not receive >= 6 cycles of T-DM1 maintenance therapy after surgery

• RANDOMIZATION - PATIENTS WITH RESIDUAL DISEASE POST NEOADJUVANT TRATUZUMAB +/- PERTUZUMAB BASED CHEMOTHERAPY (NO pCR) - (PHASE II): Have residual disease with >= 1 cm residual tumor in the breast (>= ypT1c) and/or persistent lymph node positivity after trastuzumab +/- pertuzumab based neoadjuvant chemotherapy

• RANDOMIZATION - PATIENTS WITH RESIDUAL DISEASE POST NEOADJUVANT TRATUZUMAB +/- PERTUZUMAB BASED CHEMOTHERAPY (NO pCR) - (PHASE II): Adequate tissue specimens from both pre-treatment biopsy and surgery must be submitted. Adequate tissue samples defined as core needle biopsy or incisional biopsy or excisional samples that can provide >= 3 core needle biopsies with at least 14G needle with 12 unstained sections of 5 micron thickness

• NOTE: Fine needle aspiration (FNA) sample alone is not sufficient

• RANDOMIZATION - PATIENTS WITH RESIDUAL DISEASE POST NEOADJUVANT TRATUZUMAB +/- PERTUZUMAB BASED CHEMOTHERAPY (NO pCR) - (PHASE II): Negative pregnancy test done =< 7 days prior to randomization, for persons of childbearing potential only

• NOTE: If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required

• RANDOMIZATION - PATIENTS WITH RESIDUAL DISEASE POST NEOADJUVANT TRATUZUMAB +/- PERTUZUMAB BASED CHEMOTHERAPY (NO pCR) - (PHASE II): ECOG performance status (PS) 0, 1, 2

• RANDOMIZATION - PATIENTS WITH RESIDUAL DISEASE POST NEOADJUVANT TRATUZUMAB +/- PERTUZUMAB BASED CHEMOTHERAPY (NO pCR) - (PHASE II): Willing to employ adequate contraception from the time of randomization through 6 months after the final vaccine cycle

Exclusion Criteria:

• PRE-REGISTRATION FOR ALL PATIENTS (INCLUDE SAFETY LEAD-IN): Any of the following because this study involves an investigational agent whose genotoxic, mutagenic and teratogenic effects on the developing fetus and newborn are unknown:

• Pregnant person

• Nursing person unwilling to stop breast feeding

• Person of child bearing potential who are unwilling to employ adequate contraception from the time of registration through 6 months after the final vaccine cycle

• PRE-REGISTRATION FOR ALL PATIENTS (INCLUDE SAFETY LEAD-IN): Clinical evidence of active local recurrence or distant metastases

• NOTE: All patients must have either a positron emission tomography (PET)/computed tomography (CT) or CT chest, abdomen, and pelvis with bone scan to rule out distant metastases =< 365 days prior to preregistration. If any of these is concerning, follow-up imaging or biopsy should be performed if indicated rule out distant metastases

• PRE-REGISTRATION FOR ALL PATIENTS (INCLUDE SAFETY LEAD-IN): Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens

• PRE-REGISTRATION FOR ALL PATIENTS (INCLUDE SAFETY LEAD-IN): Immunocompromised patients including patients known to be human immunodeficiency virus (HIV) positive or those on chronic steroids

• NOTE: Must be off systemic steroids at least 14 days prior to pre-registration. However, topical steroids, inhalants or steroid eye drops are permitted

• PRE-REGISTRATION FOR ALL PATIENTS (INCLUDE SAFETY LEAD-IN): Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements

• PRE-REGISTRATION FOR ALL PATIENTS (INCLUDE SAFETY LEAD-IN): Uncontrolled acute or chronic medical conditions including, but not limited to the following:

• Active infection requiring antibiotics

• Congestive heart failure with New York Heart Association class III or IV; moderate to severe objective evidence of cardiovascular disease

• Myocardial infarction or stroke =< 6 months prior to pre-registration

• Significant cardiac arrhythmia or unstable angina

• PRE-REGISTRATION FOR ALL PATIENTS (INCLUDE SAFETY LEAD-IN): Receiving any other investigational agent

• PRE-REGISTRATION FOR ALL PATIENTS (INCLUDE SAFETY LEAD-IN): Other active malignancy at time of pre-registration or =< 3 years prior to preregistration

• EXCEPTIONS: Non-melanoma skin cancer or carcinoma-in-situ (e.g. of cervix, prostate)

• NOTE: If there is a history of prior malignancy, they must not be receiving other specific treatment (cytotoxics, monoclonal antibodies, small molecule inhibitors) for their cancer

• PRE-REGISTRATION FOR ALL PATIENTS (INCLUDE SAFETY LEAD-IN): Known history of active autoimmune disease that has required systemic treatment in the =< 30 days (i.e., with use of disease modifying agents, corticosteroids, or immunosuppressive drugs) prior to pre-registration. NOTE: Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment. Patients with vitiligo, Graves disease, or psoriasis not requiring systemic treatment within the past 30 days are not excluded. Patients with Celiac disease controlled with diet modification are not excluded

• PRE-REGISTRATION FOR ALL PATIENTS (INCLUDE SAFETY LEAD-IN): Any prior hypersensitivity or adverse reaction to granulocyte-macrophage colony stimulating factor (GM-CSF)

• PRE-REGISTRATION FOR ALL PATIENTS (INCLUDE SAFETY LEAD-IN): History of trastuzumab-related cardiac toxicity requiring interruption or discontinuation of therapy, even if left ventricular ejection fraction (LVEF) fully recovered

• PRE-REGISTRATION FOR ALL PATIENTS (INCLUDE SAFETY LEAD-IN): Baseline LVEF < 50%

• PRE-REGISTRATION FOR ALL PATIENTS (INCLUDE SAFETY LEAD-IN): Failure to fully recover from acute, reversible effects of prior chemotherapy regardless of interval since last treatment

• PRE-REGISTRATION FOR ALL PATIENTS (INCLUDE SAFETY LEAD-IN): History of myocardial infarction =< 168 days (6 months) prior to pre-registration, or congestive heart failure requiring use of ongoing maintenance therapy for life threatening ventricular arrhythmias

• PRE-REGISTRATION FOR ALL PATIENTS (INCLUDE SAFETY LEAD-IN): Patients who received tamoxifen or raloxifene or another agent for prevention of breast cancer =< 2 months prior to pre-registration

Related Conditions & MeSH terms

• Breast Adenocarcinoma
• Breast Neoplasms
• Stage II Breast Cancer AJCC v6 and v7
• Stage IIA Breast Cancer AJCC v6 and v7
• Stage IIB Breast Cancer AJCC v6 and v7
• Stage III Breast Cancer AJCC v7
• Stage IIIA Breast Cancer AJCC v7
• Stage IIIB Breast Cancer AJCC v7
• Stage IIIC Breast Cancer AJCC v7

Intervention

Biological:
• Multi-epitope HER2 Peptide Vaccine TPIV100
Given ID
• Pertuzumab
permitted at physician's discretion

Other:
• Placebo Administration
Given ID

Biological:
• Sargramostim
Given ID
• Trastuzumab
therapy are at the discretion of the treating physicians
• Trastuzumab Emtansine
at the discretion of the treating physicians.

Locations

Country	Name	City	State
United States	Emory University Hospital/Winship Cancer Institute	Atlanta	Georgia
United States	University of Maryland/Greenebaum Cancer Center	Baltimore	Maryland
United States	City of Hope Comprehensive Cancer Center	Duarte	California
United States	Essentia Health NCI Community Oncology Research Program	Duluth	Minnesota
United States	Marshfield Medical Center-EC Cancer Center	Eau Claire	Wisconsin
United States	Inova Fairfax Hospital	Falls Church	Virginia
United States	University of Florida Health Science Center - Gainesville	Gainesville	Florida
United States	Saint Vincent Hospital Cancer Center Green Bay	Green Bay	Wisconsin
United States	Mayo Clinic in Florida	Jacksonville	Florida
United States	UC San Diego Moores Cancer Center	La Jolla	California
United States	Dartmouth Hitchcock Medical Center/Dartmouth Cancer Center	Lebanon	New Hampshire
United States	Dean Hematology and Oncology Clinic	Madison	Wisconsin
United States	Middlesex Hospital	Middletown	Connecticut
United States	Vanderbilt University/Ingram Cancer Center	Nashville	Tennessee
United States	University Medical Center New Orleans	New Orleans	Louisiana
United States	University of Nebraska Medical Center	Omaha	Nebraska
United States	Illinois CancerCare-Peoria	Peoria	Illinois
United States	FirstHealth of the Carolinas-Moore Regional Hospital	Pinehurst	North Carolina
United States	Mayo Clinic in Rochester	Rochester	Minnesota
United States	Coborn Cancer Center at Saint Cloud Hospital	Saint Cloud	Minnesota
United States	Washington University School of Medicine	Saint Louis	Missouri
United States	Guthrie Medical Group PC-Robert Packer Hospital	Sayre	Pennsylvania
United States	Mayo Clinic in Arizona	Scottsdale	Arizona
United States	Siouxland Regional Cancer Center	Sioux City	Iowa
United States	Banner University Medical Center - Tucson	Tucson	Arizona
United States	University of Arizona Cancer Center-North Campus	Tucson	Arizona
United States	Carle Cancer Center NCI Community Oncology Research Program	Urbana	Illinois
United States	Lexington Medical Center	West Columbia	South Carolina
United States	Cleveland Clinic Florida	West Palm Beach	Florida
United States	Yuma Regional Medical Center	Yuma	Arizona

Sponsors (2)

Lead Sponsor	Collaborator
Academic and Community Cancer Research United	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Invasive disease-free survival (iDFS) between the 2 arms	iDFS will be defined from the time of randomization to ipsilateral invasive breast tumor recurrence, regional invasive breast cancer recurrence, distant recurrence, death attributable to any cause, including breast cancer, non-breast cancer, or unknown cause, contralateral invasive breast cancer, or second primary non-breast invasive cancer. Will be based on stratified log-rank test at one-sided 0.01 level in an intention-to-treat population, where the stratification is by the randomization stratification factors. The Cox proportional hazards model will be used to adjust for the trial stratification factors (hormone receptor, human leukocyte antigen A classification, status and clinical stage). Subgroup analyses of iDFS will also be performed by stratification factors and other baseline characteristics, with the caveat that statistical power for these subgroup analyses may be limited.	From time of randomization to recurrence, invasive breast cancer or death, assessed up to 5 years
Secondary	Overall survival	defined as the time from randomization to the date of death due to any cause. Patients who are lost to follow-up for OS will be censored at the date the subject was last known to be alive	From randomization to the date of death due to any cause, assessed up to 5 years
Secondary	Incidence of adverse events (AEs)	Will be assessed according to Common Terminology Criteria for Adverse Events 5.0 and defined as adverse events that are classified as either unrelated, unlikely to be related, possibly, probably, or definitely related to the study treatment. The maximum grade for each type of toxicity will be recorded for each patient, and frequency tables will be reviewed by primary disease site to determine toxicity patterns. Frequency tables will be generated to summarize the occurrence of treatment-related AE's by treatment arms. Comparisons of the rates of individual AE's will be done using tests of proportions such as Fisher's exact test or Chi-squared test. Additional analysis will use the Cochran-Mantel-Haenszel chi-squared test with study stratification factors.	Up to 24 months
Secondary	Immunogenicity assessment	To evaluate immunogenicity of multi-epitope HER2 vaccine in combination with T-DM1 maintenance therapy.	Up to 5 years
Secondary	Complete pathological response	Will be assessed using immune-related tissue and blood biomarkers.	Baseline
Secondary	Vaccine induced HER2-specific T cell responses	Will be defined as a 2-fold or greater increase in HER2-specific antibody concentration from pre-treatment levels at any point during treatment or HER2-specific antibodies above the lower limit of detection at any point during treatment if pre-treatment levels were non-detectable. Antibody response frequency at the post-treatment initiation time points will be compared among arms using a chi-squared test. Antibody response magnitude at the post-treatment initiation time point will be compared among arms using an analysis of variance F-test followed by Tukey pairwise comparisons between pairs of arms. Likelihood of antibody response at the post-treatment initiation time point will be compared among arms using logistic regression (the dependent variable is antibody response [yes/no] at the post-treatment initiation time point; the independent variables are the antibody response [yes/no] at the pre-treatment time point and a categorical variable capturing arm).	Baseline up to 24 months