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

Plain English Summary

A Vaccine (STEMVAC) With Standard Endocrine-Based Therapy or Chemotherapy for the Treatment of Metastatic Hormone Receptor Positive, HER2 Negative Breast Cancer is a Phase 2 clinical trial sponsored by University of Washington studying Anatomic Stage IV Breast Cancer AJCC v8, Metastatic HER2-Negative Breast Carcinoma, Metastatic Hormone Receptor-Positive Breast Carcinoma. This trial tests a new vaccine called STEMVAC, given alongside standard treatments, to see if it can help fight hormone-receptor-positive, HER2-negative metastatic breast cancer. It is for patients with this specific type of advanced breast cancer who are either receiving initial treatment with endocrine therapy and a targeted drug, or who have progressed on prior endocrine therapies. Participation involves receiving the STEMVAC vaccine, standard therapy (either endocrine therapy with a targeted drug or chemotherapy), and potentially undergoing tumor biopsies. Alternative treatments include standard endocrine therapy, targeted drugs like CDK4/6 inhibitors, and chemotherapy, depending on the patient's treatment history. The trial aims to enroll 40 participants.

Official 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, including abemaciclib, 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.

Who Can Participate

Here is what you need to know about eligibility for this trial. Adults aged 18 and older with a confirmed diagnosis of hormone-receptor-positive, HER2-negative or HER2-low metastatic breast cancer. Patients must be starting or have progressed on specific types of endocrine-based therapies and be in good general health, with adequate blood counts and organ function. Individuals with certain heart conditions, autoimmune diseases requiring chronic steroids, recent major surgery, or active infections may not be eligible. Women who can become pregnant must agree to use effective contraception, and patients with a history of HIV, Hepatitis B, or Hepatitis C may be excluded. This trial is studying Anatomic Stage IV Breast Cancer AJCC v8, Metastatic HER2-Negative Breast Carcinoma, Metastatic Hormone Receptor-Positive Breast Carcinoma, so participants generally need a confirmed diagnosis. The trial is currently accepting new participants.

What They're Measuring

The primary outcomes measure how often side effects occur and how well the vaccine stimulates an immune response, indicating its safety and potential to activate the body's defenses against cancer. The specific primary outcome measures are: Incidence of adverse events (AEs) (Up to 3 years after completion of study treatment); Incidence of immunogenicity (Pre-vaccine up to after 2 booster doses of STEMVAC vaccine (Up to 40 weeks)). These endpoints are how researchers determine whether the treatment is effective and will form the basis of any future regulatory submissions.

About This Phase

This trial is in Phase 2, which tests whether the treatment actually works against the target condition. Phase 2 trials involve 100-300 patients and continue to monitor safety while evaluating effectiveness. This phase often tests different dosages to find the optimal amount. About 33% of Phase 2 drugs advance to Phase 3. If successful, the treatment will move to large-scale Phase 3 trials needed for FDA approval.

Why This Trial Matters

This trial addresses a need for new treatments for metastatic hormone receptor-positive breast cancer by exploring a novel vaccine approach to harness the immune system against the cancer. Phase 2 success would typically lead to larger Phase 3 trials needed for regulatory approval. This research targets Anatomic Stage IV Breast Cancer AJCC v8, Metastatic HER2-Negative Breast Carcinoma, Metastatic Hormone Receptor-Positive Breast Carcinoma, where improved treatment options are needed.

Investor Insight

This trial investigates a novel immunotherapy for a common subtype of breast cancer, potentially offering a new treatment option and representing an investment in the growing field of cancer vaccines. Phase 2 trials have approximately a 15-20% chance of eventually gaining FDA approval.

Is This Trial Right for Me?

Ask your doctor about the specific standard treatments you will receive alongside the vaccine and what the potential benefits and risks are. Be prepared for regular clinic visits for vaccine administration, treatment, and potential tumor biopsies to monitor your response. Understand that participation may involve up to two biopsies during the study to collect tissue samples for research. This trial is currently recruiting participants. The trial is being conducted at 1 site. Always discuss clinical trial participation with your healthcare provider before making any decisions. This information is for educational purposes only and is not medical advice.

AI-generated analysis for educational purposes only. This is not medical advice. Discuss clinical trial participation with your doctor. Data sourced from ClinicalTrials.gov.

Study Design

• Study Type: INTERVENTIONAL
• Allocation: NON_RANDOMIZED
• Model: PARALLEL
• Masking: NONE
• Enrollment: 40 participants

Interventions

• BIOLOGICAL: CD105/Yb-1/SOX2/CDH3/MDM2-polyepitope Plasmid DNA Vaccine — Given ID
• DRUG: Capecitabine — Given SOC capecitabine
• PROCEDURE: Computed Tomography — Undergo CT or ultrasound-guided biopsies
• DRUG: Cyclin-Dependent Kinase 4 Inhibitor — Given SOC CDK4/6i
• DRUG: Cyclin-Dependent Kinase 6 Inhibitor — Given SOC CDK4/6i

Primary Outcomes

• Incidence of adverse events (AEs) (Up to 3 years after completion of study treatment)
• Incidence of immunogenicity (Pre-vaccine up to after 2 booster doses of STEMVAC vaccine (Up to 40 weeks))

Secondary Outcomes

• 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)

Full 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

Trial Locations

• Fred Hutch/University of Washington Cancer Consortium, Seattle, Washington, United States

Frequently Asked Questions

Related Conditions

• Breast Cancer
• Metastatic Breast Cancer
• Hormone Receptor Positive Breast Cancer
• HER2 Negative Breast Cancer
• Stage IV Breast Cancer
• Endocrine-Resistant Breast Cancer
• Metastatic Cancer
• Cancer Immunotherapy
• Vaccine Therapy
• Oncology

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