Concurrent WOKVAC Vaccination, Chemotherapy, and HER2-Targeted Monoclonal Antibody Therapy Before Surgery for the Treatment of Patients With Breast Cancer

NCT04329065 | Recruiting Phase 2 DMC FDA Drug

• 4 other identifiers: RG1005296NCI-2020-01662W81XWH-16-1-038510159
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 1

Brief Summary

This phase II trial studies the immunologic response and side effects of using the WOKVAC vaccine in combination with chemotherapy and HER2-targeted monoclonal antibody therapy before surgery in treating patients with breast cancer. Vaccines like WOKVAC are made from tumor-associated antigens which may help the body build an effective immune response to kill tumor cells. Chemotherapy drugs, such as paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Trastuzumab and pertuzumab are forms of targeted therapy because they work by attaching themselves to specific molecules (receptors) on the surface of tumor cells, known as HER2 receptors. When trastuzumab and pertuzumab attach to HER2 receptors, the signals that tell the cells to grow are blocked and the tumor cell may be marked for destruction by the body's immune system. Giving the WOKVAC vaccine at the same time (concurrently) with paclitaxel, trastuzumab, and pertuzumab before surgery may kill more tumor cells.

Conditions

Anatomic Stage I Breast Cancer AJCC v8; Anatomic Stage II Breast Cancer AJCC v8; Anatomic Stage III Breast Cancer AJCC v8

Keywords

Breast

Outcome Measures

Primary Outcomes (1)

• Enumeration of the number of T-bet+, CD4+, and CD8+ T-cells in tumor infiltrating lymphocytes (TIL) after combination immune-chemotherapy

  Tumor tissue will be collected from prior diagnostic tumor biopsies as well as from an ultrasound guided core needle biopsy performed on day 13 of cycle 3. Tumor biopsies collected pre- and post- trial therapy will be processed and evaluated by immunohistochemistry for differences and changes in T cell content and T cell subtype. Specifically, will evaluate the differences in the presence of T-bet+ CD4+ and CD8+ T cells, a T cell subtype recently recognized to influence both the induced human epidermal growth factor receptor 2 (HER2)-specific cellular immunity and clinical outcomes. Changes in the tumor content of T-bet+ CD4+ and CD8+ T cells between the pre- and post-trial therapy time points will be evaluated.

  Up to completion of surgical resection

Secondary Outcomes (2)

• Incidence of adverse events

  Up to 5 years

• Induction of type 1 helper cell (Th1) immunity against HER2, IGF-1R, and IGFBP2

  Up to day 13 of cycle 4 (each cycle is 21 days)

Study Arms (1)

Treatment (WOKVAC, paclitaxel, trastuzumab, pertuzumab)

EXPERIMENTAL

Patients receive WOKVAC ID on day 13. Treatment repeats for up to 3 cycles in the absence of disease progression or unacceptable toxicity. Patients also receive paclitaxel via infusion on days 1, 8, and 15 or docetaxel IV and carboplatin IV on day 1, and trastuzumab IV and pertuzumab IV on day 1. The chemo and trastuzumab and pertuzumab will most likely be given by the patient's own oncologist per standard of care. Treatment repeats for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo ultrasound imaging or magnetic resonance imaging and biopsy on study and blood sample collection throughout the study.

Biological: pUMVC3-IGFBP2-HER2-IGF1R Plasmid DNA Vaccine; Drug: Paclitaxel; Biological: Trastuzumab; Biological: Pertuzumab; Drug: Docetaxel; Drug: Carboplatin; Procedure: Ultrasound Imaging; Procedure: Biopsy Procedure; Procedure: Biospecimen Collection

Interventions

pUMVC3-IGFBP2-HER2-IGF1R Plasmid DNA Vaccine BIOLOGICAL

Given ID

Also known as: pUMVC3-IGFBP2-HER2-IGF1R, pUMVC3-IGFBP2-HER2-IGF1R Vaccine, WOKVAC, WOKVAC Vaccine

Treatment (WOKVAC, paclitaxel, trastuzumab, pertuzumab)

Paclitaxel DRUG

Given via infusion

Also known as: Anzatax, Asotax, Bristaxol, Praxel, Taxol, Taxol Konzentrat

Treatment (WOKVAC, paclitaxel, trastuzumab, pertuzumab)

Trastuzumab BIOLOGICAL

Given IV

Also known as: Anti-c-erbB2 Monoclonal Antibody, Anti-ERB-2, Anti-erbB2 Monoclonal Antibody, Anti-HER2/c-erbB2 Monoclonal Antibody, Herceptin, Herceptin Biosimilar PF-05280014, Herceptin Trastuzumab Biosimilar PF-05280014, Herzuma, Disulfide with Human-Mouse Monoclonal RhuMab HER2 Light Chain, MoAb HER2, Monoclonal Antibody c-erb-2, Monoclonal Antibody HER2, Ogivri, Ontruzant, rhuMAb HER2, Trastuzumab Biosimilar ABP 980, Trastuzumab Biosimilar ALT02, trastuzumab biosimilar EG12014, Trastuzumab Biosimilar HLX02, Trastuzumab Biosimilar PF-05280014, Trastuzumab Biosimilar SB3, Trastuzumab-dkst, Trastuzumab-DTTB, Trastuzumab-pkrb, Trastuzumab-QYYP, Trazimera, Trastuzumab Biosimilar SIBP-01

Treatment (WOKVAC, paclitaxel, trastuzumab, pertuzumab)

Pertuzumab BIOLOGICAL

Given IV

Also known as: 2C4 Antibody, Immunoglobulin G1, Anti-(Human V (Receptor)) (Human-Mouse Monoclonal 2C4 Heavy Chain), Disulfide with Human-Mouse Monoclonal 2C4 Kappa-Chain, MoAb 2C4, Monoclonal Antibody 2C4, Omnitarg, Perjeta, rhuMAb2C4, RO4368451, Pertuzumab Biosimilar HS627, Pertuzumab Biosimilar EG1206A, Pertuzumab Biosimilar HLX11

Treatment (WOKVAC, paclitaxel, trastuzumab, pertuzumab)

Docetaxel DRUG

Given IV

Also known as: RP-56976, RP56976, Taxotere, Taxotere Injection Concentrate

Treatment (WOKVAC, paclitaxel, trastuzumab, pertuzumab)

Carboplatin DRUG

Given IV

Also known as: Paraplatin, Platinwas, Ribocarbo

Treatment (WOKVAC, paclitaxel, trastuzumab, pertuzumab)

Ultrasound Imaging PROCEDURE

Undergo ultrasound imaging

Also known as: US

Treatment (WOKVAC, paclitaxel, trastuzumab, pertuzumab)

Biopsy Procedure PROCEDURE

Undergo biopsy

Also known as: Bx

Treatment (WOKVAC, paclitaxel, trastuzumab, pertuzumab)

Biospecimen Collection PROCEDURE

Undergo blood sample collection

Also known as: Biological Sample Collection

Treatment (WOKVAC, paclitaxel, trastuzumab, pertuzumab)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must be at least \>= 18 years of age
• Clinical stage I-III breast cancer, HER2+ (per American Society of Clinical Oncology \[ASCO\]/College of American Pathologists \[CAP\] guideline update, 2018), regardless of estrogen receptor (ER)/ progesterone receptor (PR) status and planning to undergo neoadjuvant therapy with either paclitaxel, trastuzumab, and pertuzumab (THP) or docetaxel, carboplatin, trastuzumab, and pertuzumab (TCHP)
• Patients who have received prior neoadjuvant chemotherapy are allowed but may only receive paclitaxel, trastuzumab, and pertuzumab for the duration the study
• Subjects with Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1
• White blood cell (WBC) \>= 3000/mm\^3 (within 4 weeks of initiating study treatment)
• Lymphocyte count \>= 500/mm\^3 (within 4 weeks of initiating study treatment)
• Absolute neutrophil count (ANC) \>= 1,500/ uL (within 4 weeks of initiating study treatment)
• Platelets \>= 75,000/ uL (within 4 weeks of initiating study treatment)
• Total bilirubin =\< 1.5 x institutional upper limit of normal (ULN), except patients with Gilbert's syndrome in whom total bilirubin must be \< 3.0 mg/dL (within 4 weeks of initiating study treatment)
• Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =\< 3 x institutional upper limit of normal (ULN) (within 4 weeks of initiating study treatment)
• Creatinine =\< 2.0 mg/dL or creatinine clearance \> 30 ml/min (within 4 weeks of initiating study treatment)
• Left ventricular ejection fraction (LVEF) \>= lower limit of normal for institution performing the multi-gated acquisition (MUGA) or echocardiogram (ECHO) done within 3 months of initiating study treatment
• Female patients of child-bearing potential must agree to use dual methods of contraception and have a negative urine pregnancy test at screening, and male patients must use an effective barrier method of contraception if sexually active with a female of child-bearing potential. Acceptable methods of contraception are condoms with contraceptive foam, oral, implantable or injectable contraceptives, contraceptive patch, intrauterine device, diaphragm with spermicidal gel, or a sexual partner who is surgically sterilized or post-menopausal. For both male and female patients, effective methods of contraception must be used throughout the study and for three months following the last vaccine
• Ability to understand and willingness to sign a written informed consent document

You may not qualify if:

• Patients with any of the following cardiac conditions:
• Symptomatic restrictive cardiomyopathy
• Dilated cardiomyopathy
• Unstable angina within 4 months prior to enrollment
• New York Heart Association functional class III-IV heart failure on active treatment
• Symptomatic pericardial effusion
• Uncontrolled autoimmune disease requiring active systemic treatment
• Known hypersensitivity reaction to the granulocyte-macrophage colony stimulating factor (GM-CSF) adjuvant; any known contra-indication to GM-CSF
• Pregnant or breast feeding
• Known human immunodeficiency virus (HIV)-positive
• History of uncontrolled diabetes
• Known current or a history of hepatitis B or C virus, including chronic and dormant states, unless disease has been treated and confirmed cleared
• Major surgery within the 4 weeks prior to initiation of study vaccine
• Current use of immunosuppressive agents or systemic corticosteroids. Topical, ocular, intra-articular, intranasal, inhalational corticosteroids (with minimal systemic absorption) are allowed. Patients who have received systemic corticosteroids =\< 30 days prior to starting study drug will be excluded
• \* NOTE: Steroids given as supportive care for the neoadjuvant chemotherapy regimens is allowable per standard of care

Sponsors & Collaborators

• University of Washington: lead
• United States Department of Defense: collaborator

Study Sites (1)

Fred Hutch/University of Washington Cancer Consortium

Seattle, Washington, 98109, United States

RECRUITING

MeSH Terms

Interventions

Paclitaxel; Taxes; Trastuzumab; PF-05280014; Disulfides; Ogivri; Ontruzant; trastuzumab biosimilar HLX02; pertuzumab; 2C4 antibody; Immunoglobulin G; Docetaxel; Carboplatin; High-Energy Shock Waves; Biopsy

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Economics; Health Care Economics and Organizations; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Sulfides; Anions; Ions; Electrolytes; Inorganic Chemicals; Hydrogen Sulfide; Sulfur Compounds; Immunoglobulin Isotypes; Coordination Complexes; Ultrasonic Waves; Sound; Radiation, Nonionizing; Radiation; Physical Phenomena; Cytodiagnosis; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Specimen Handling; Diagnostic Techniques, Surgical; Surgical Procedures, Operative; Investigative Techniques

Study Officials

• William Gwin

  Fred Hutch/University of Washington Cancer Consortium

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jennifer Childs

CONTACT

206-616-2305; childj@uw.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 30, 2020
• First Posted: April 1, 2020
• Study Start: April 20, 2022
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2027
• Last Updated: May 19, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)