NCT07112053

Brief Summary

This phase II trial studies how well a vaccine, STEMVAC, works in combination with standard endocrine-based therapy (ET) with a CDK4/6 targeted drug therapy, or with the chemotherapy drug capecitabine, in treating patients with hormone receptor (HR)-positive, HER2-negative breast cancer that has spread from where it first started (primary site) to other places in the body (metastatic). STEMVAC is designed to target proteins that cancer cells use when they become more aggressive and start to spread, and it is believed to work by boosting the immune system to recognize and destroy the invader tumor cells that are causing the disease. Standard ET is treatment that adds, blocks, or removes hormones in order to slow or stop the growth of cancer. Standard CDK4/6 inhibitors may stop the growth of tumor cells and may kill them by blocking some of the enzymes needed for cell growth. Capecitabine is in a class of medications called antimetabolites. It is taken up by tumor cells and breaks down into fluorouracil, a substance that kills tumor cells. Giving STEMVAC in combination with standard ET or chemotherapy may be an effective treatment for metastatic HR positive, HER2 negative breast cancer.

Trial Health

77
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
40

participants targeted

Target at P25-P50 for phase_2

Timeline
32mo left

Started Nov 2025

Typical duration for phase_2

Geographic Reach
1 country

1 active site

Status
recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress15%
Nov 2025Dec 2028

First Submitted

Initial submission to the registry

July 18, 2025

Completed
21 days until next milestone

First Posted

Study publicly available on registry

August 8, 2025

Completed
3 months until next milestone

Study Start

First participant enrolled

November 17, 2025

Completed
2.7 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

July 31, 2028

Expected
5 months until next milestone

Study Completion

Last participant's last visit for all outcomes

December 31, 2028

Last Updated

March 9, 2026

Status Verified

December 1, 2025

Enrollment Period

2.7 years

First QC Date

July 18, 2025

Last Update Submit

March 6, 2026

Conditions

Outcome Measures

Primary Outcomes (2)

  • Incidence of adverse events (AEs)

    Safety and systemic toxicity will be determined by chemical and clinical parameters evaluated at various time points. Toxicity grading will be evaluated according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events version 6.0 and monitoring of AEs will be done per Food and Drug Administration and NCI guidelines. The type and grade of toxicities noted during the immunization regimen will be summarized. The duration of toxicities will also be summarized using descriptive statistics such as mean and standard deviation. All AEs noted by the investigator will be tabulated according to the affected body system. The frequency and severity of adverse events will be summarized with a proportion and a 95% confidence interval (CI).

    Up to 3 years after completion of study treatment

  • Incidence of immunogenicity

    Will be defined as the sum of the interferon gamma enzyme-linked immunosorbent spot of all STEMVAC antigens on blood samples collected pre-vaccine as compared to 1-month post dose #3 of the STEMVAC vaccine and again after 2 booster doses of STEMVAC vaccine. Both incidence and magnitude will be assessed. Immune responses will be summarized with mean and standard deviation or median and range (if skewness is observed) over time, the change over time will be summarized with graphs, and also analyzed using linear mixed-effects regression models with normalizing transformation if necessary.

    Pre-vaccine up to after 2 booster doses of STEMVAC vaccine (Up to 40 weeks)

Secondary Outcomes (3)

  • Progression-free survival (PFS)

    From the start of treatment to the worsening of cancer as determined by primary treating oncologist or death whichever occurs first, assessed up to 3 years after completion of study treatment

  • Circulating tumor DNA (ctDNA)

    Up to 3 years after completion of study treatment

  • Elimination of cancer cells associated with epithelial to mesenchymal transformation (EMT)

    Up to 3 years after completion of study treatment

Study Arms (2)

Cohort 1 (STEMVAC, ET + CDK4/6i)

EXPERIMENTAL

After completion of 2 cycles of SOC ET + CDK4/6i therapy, patients receive STEMVAC ID on the following schedule: 1) Three "priming" doses every 28 days; 2) Two "booster" doses at 6 and 9 months after "priming" dose #3; and 3) Additional "booster" doses every 6 months in the absence of disease progression or unacceptable toxicity. Patients also undergo CT or ultrasound-guided biopsies, as well as collection of blood samples and CT or PET scans throughout the trial.

Biological: CD105/Yb-1/SOX2/CDH3/MDM2-polyepitope Plasmid DNA VaccineProcedure: Computed TomographyDrug: Cyclin-Dependent Kinase 4 InhibitorDrug: Cyclin-Dependent Kinase 6 InhibitorDrug: Hormone TherapyProcedure: Positron Emission TomographyProcedure: Ultrasound ImagingProcedure: Biopsy ProcedureProcedure: Biospecimen Collection

Cohort 2 (STEMVAC, capecitabine)

EXPERIMENTAL

After completion of 1 cycle of SOC capecitabine treatment, patients receive STEMVAC ID on the following schedule: 1) Three "priming" doses every 28 days; 2) Two "booster" doses at 6 and 9 months after "priming" dose #3; and 3) Additional "booster" doses every 6 months in the absence of disease progression or unacceptable toxicity. Patients also undergo CT or ultrasound-guided biopsies, collection of blood samples, and FES PET scans, as well as CT or PET scans throughout the trial.

Biological: CD105/Yb-1/SOX2/CDH3/MDM2-polyepitope Plasmid DNA VaccineDrug: CapecitabineProcedure: Computed TomographyDrug: F-18 16 Alpha-FluoroestradiolProcedure: Positron Emission TomographyProcedure: Ultrasound ImagingProcedure: Biopsy ProcedureProcedure: Biospecimen Collection

Interventions

Given ID

Also known as: STEMVAC, STEMVAC Th1 Polyepitope Plasmid-based Vaccine, CD105/Yb-1/SOX2/CDH3/MDM2 Plasmid Vaccine
Cohort 1 (STEMVAC, ET + CDK4/6i)Cohort 2 (STEMVAC, capecitabine)

Given SOC capecitabine

Also known as: Ro 09-1978/000, Xeloda
Cohort 2 (STEMVAC, capecitabine)

Undergo CT or ultrasound-guided biopsies

Also known as: CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography, Computerized axial tomography (procedure), Computerized Tomography, Computerized Tomography (CT) scan, CT, CT Scan, tomography
Cohort 1 (STEMVAC, ET + CDK4/6i)Cohort 2 (STEMVAC, capecitabine)

Given SOC CDK4/6i

Also known as: CDK4 Inhibitor
Cohort 1 (STEMVAC, ET + CDK4/6i)

Given SOC CDK4/6i

Also known as: CDK6 Inhibitor
Cohort 1 (STEMVAC, ET + CDK4/6i)

Undergo FES PET

Also known as: 16 alpha-fluroestradiol-17 beta, F-18 FES, FES, Fluorine-18 16 alpha-fluoroestradiol, Fluoroestradiol F-18
Cohort 2 (STEMVAC, capecitabine)

Given SOC ET

Also known as: Chemotherapy-Hormones/Steroids, Endocrine Therapy, Hormonal, Hormonal Therapy, hormone treatment, Hormones
Cohort 1 (STEMVAC, ET + CDK4/6i)

Undergo PET or FES PET

Also known as: Medical Imaging, Positron Emission Tomography, PET, PET Scan, Positron emission tomography (procedure), Positron Emission Tomography Scan, Positron-Emission Tomography, PT
Cohort 1 (STEMVAC, ET + CDK4/6i)Cohort 2 (STEMVAC, capecitabine)

Undergo CT or ultrasound-guided biopsies

Also known as: 2-Dimensional Grayscale Ultrasound Imaging, 2-Dimensional Ultrasound Imaging, 2D-US, Ultrasonography, Ultrasound, Ultrasound Test, Ultrasound, Medical, US
Cohort 1 (STEMVAC, ET + CDK4/6i)Cohort 2 (STEMVAC, capecitabine)

Undergo CT or ultrasound-guided biopsies

Also known as: Biopsy, BIOPSY_TYPE, Bx
Cohort 1 (STEMVAC, ET + CDK4/6i)Cohort 2 (STEMVAC, capecitabine)

Undergo collection of blood samples

Also known as: Biological Sample Collection
Cohort 1 (STEMVAC, ET + CDK4/6i)Cohort 2 (STEMVAC, capecitabine)

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Patients must be at least ≥ 18 years of age
  • Histologically confirmed hormone receptor positive metastatic breast cancer: Tumors that are positive for estrogen receptor (ER) and/or progesterone receptor (PR)
  • HER2-negative or HER2-low will be included and defined as:
  • + HER2 expression by immunohistochemistry (IHC) OR
  • Fluorescence in situ hybridization (FISH) negative OR
  • HER2 2+ and FISH negative
  • HER2 low per standard of care in breast cancer
  • Patients should be receiving the following therapies to be eligible for the study:
  • Cohort 1: First or second line of endocrine therapy in the metastatic setting, in combination with a CDK4/6 inhibitor. Patients must have completed at least 2 cycles of CDK4/6 inhibitor. Patients who have stopped endocrine therapy for intolerance but remain on abemaciclib monotherapy will be considered for enrollment at the PI's discretion
  • Cohort 2: Progressed on endocrine-based therapies and after completion of at least 1 cycle of capecitabine
  • Subjects with Eastern Cooperative Oncology Group (ECOG) Performance Status Score of 0 or 1
  • Willing to undergo up to two serial biopsies while on study
  • Have at least 1 site of disease confirmed by the treating oncologist that could be biopsied during treatment
  • White blood cell (WBC) ≥ 2000/mm\^3 (within 28 days of receiving the study vaccine)
  • Lymphocyte count ≥ 500/mm\^3 (within 28 days of receiving the study vaccine)
  • +7 more criteria

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 hypertension
  • Uncontrolled cardiac arrhythmias
  • Patients with any autoimmune disease/comorbidity that require chronic steroids or immunosuppressants
  • A non-breast malignancy requiring radiation or systemic therapy within last 5 years
  • 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 history of human immunodeficiency virus (HIV) infection, hepatitis B (e.g., hepatitis B virus surface antigen \[HBsAg\] reactive), or hepatitis C (e.g., hepatitis C virus \[HCV\] ribonucleic acid \[RNA\] \[qualitative\] is detected)
  • 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, and inhalational corticosteroids (with minimal systemic absorption) are allowed. Patients who have received systemic corticosteroids ≤ 30 days prior to starting study drug will be excluded
  • +5 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Fred Hutch/University of Washington Cancer Consortium

Seattle, Washington, 98109, United States

RECRUITING

MeSH Terms

Interventions

CapecitabineCyclin-Dependent Kinase Inhibitor p16Cyclin-Dependent Kinase Inhibitor p1816-fluoroestradiolSteroidsHormonesMagnetic Resonance SpectroscopyHigh-Energy Shock WavesBiopsy

Intervention Hierarchy (Ancestors)

DeoxycytidineCytidinePyrimidine NucleosidesPyrimidinesHeterocyclic Compounds, 1-RingHeterocyclic CompoundsFluorouracilUracilPyrimidinonesDeoxyribonucleosidesNucleosidesNucleic Acids, Nucleotides, and NucleosidesCyclin-Dependent Kinase Inhibitor ProteinsIntracellular Signaling Peptides and ProteinsPeptidesAmino Acids, Peptides, and ProteinsCell Cycle ProteinsProteinsTumor Suppressor ProteinsNeoplasm ProteinsFused-Ring CompoundsPolycyclic CompoundsHormones, Hormone Substitutes, and Hormone AntagonistsPhysiological Effects of DrugsPharmacologic ActionsChemical Actions and UsesSpectrum AnalysisChemistry Techniques, AnalyticalInvestigative TechniquesUltrasonic WavesSoundRadiation, NonionizingRadiationPhysical PhenomenaCytodiagnosisCytological TechniquesClinical Laboratory TechniquesDiagnostic Techniques and ProceduresDiagnosisSpecimen HandlingDiagnostic Techniques, SurgicalSurgical Procedures, Operative

Study Officials

  • Natasha Hunter, MD

    Fred Hutch/University of Washington Cancer Consortium

    PRINCIPAL INVESTIGATOR

Central Study Contacts

Research Coordinator(s)

CONTACT

Study Design

Study Type
interventional
Phase
phase 2
Allocation
NON RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

July 18, 2025

First Posted

August 8, 2025

Study Start

November 17, 2025

Primary Completion (Estimated)

July 31, 2028

Study Completion (Estimated)

December 31, 2028

Last Updated

March 9, 2026

Record last verified: 2025-12

Data Sharing

IPD Sharing
Will not share

Locations