STEMVAC vaccine with hormone therapy plus CDK4/6 inhibitor or capecitabine for metastatic HR-positive, HER2-negative breast cancer

A Phase II Study of STEMVAC Vaccine Therapy for Patients With Hormone Receptor Positive Metastatic Breast Cancer

This trial tests whether adding the STEMVAC vaccine to standard hormone therapy with a CDK4/6 drug, or to capecitabine chemotherapy, helps people with metastatic hormone receptor–positive, HER2‑negative breast cancer.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 40 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: University of Washington (Academic / other)
• Drugs / interventions: radiation, chemotherapy
• Locations: 1 site (Seattle, Washington)
• Trial ID: NCT07112053 on ClinicalTrials.gov

What this trial studies

This phase II trial gives a multi‑epitope plasmid DNA vaccine (STEMVAC) together with standard endocrine-based therapy plus a CDK4/6 inhibitor for endocrine‑sensitive patients or with capecitabine for endocrine‑resistant patients. Participants are enrolled into two cohorts based on endocrine sensitivity and receive three monthly intradermal priming doses followed by boosters at months 6 and 9 and then every 6 months if there is no progression or unacceptable toxicity. The protocol includes serial image‑guided biopsies, blood sampling, and CT or PET imaging to measure tumor response and immune effects. After study treatment, participants are followed every six months for three years.

Who should consider this trial

Good fit: Ideal candidates are adults with metastatic hormone receptor–positive, HER2‑negative breast cancer who are either on first‑ or second‑line endocrine therapy with a CDK4/6 inhibitor (Cohort 1) or have progressed on endocrine therapy and are starting capecitabine (Cohort 2).

Not a fit: Patients whose tumors are not hormone receptor–positive and HER2‑negative, those needing immediate alternative treatment for rapidly progressing disease, or those unable to undergo intradermal vaccination or research biopsies are unlikely to benefit from this protocol.

Why it matters

Potential benefit: If successful, adding STEMVAC could help the immune system control metastatic HR‑positive, HER2‑negative breast cancer longer and potentially delay disease progression when combined with standard therapies.

How similar studies have performed: Tumor‑targeted DNA vaccines have produced immune responses and occasional clinical responses in small early‑phase studies, but their benefit in metastatic HR‑positive breast cancer—especially combined with endocrine or CDK4/6 therapy—remains experimental and not yet widely proven.

Eligibility criteria

Inclusion Criteria:

* 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:

  * 0-1+ 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)
* Absolute neutrophil count (ANC) ≥ 800/µL (within 28 days of receiving the study vaccine)
* Platelets ≥ 75,000/µL (within 28 days of receiving the study vaccine)
* 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 28 days of receiving the study vaccine)
* Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ≤ 3 x institutional upper limit of normal (ULN) (within 28 days of receiving the study vaccine)
* Creatinine ≤ 2.0 mg/dL or creatinine clearance \> 30 mL/min (within 28 days of receiving the study vaccine)
* 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 postmenopausal. Effective methods of contraception must be used throughout the study and until the end of treatment on study
* Must have recovered from major infections and/or surgical procedures; and in the opinion of the investigator, not have any significant active concurrent medical illnesses or condition precluding protocol treatment

Exclusion Criteria:

* 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
* Patient is currently enrolled in any other clinical protocol or investigational trial that involves administration of experimental therapy and/or therapeutic devices, or investigational drug

  * NOTE: Biomarker or tissue collection or any other non-interventional clinical trial enrollment is allowed
* Must be 14 days between a non-study vaccine and any STEMVAC vaccination

  * NOTE: The minimum of 14 days does not apply to the tetanus and diphtheria (Td) vaccine
* Any condition that may interfere with the patient's participation in the study per treating oncologist

Where this trial is running

Seattle, Washington

• Fred Hutch/University of Washington Cancer Consortium — Seattle, Washington, United States (Recruiting)

Study contacts

• Principal investigator: Natasha Hunter, MD — Fred Hutch/University of Washington Cancer Consortium
• Study coordinator: Research Coordinator(s)

Conditions Anatomic Stage IV Breast Cancer AJCC v8; Metastatic HER2-Negative Breast Carcinoma; Metastatic Hormone Receptor-Positive Breast Carcinoma