Vaccine targeting HER2 in locally advanced breast cancer

Phase I Trial of a Chimeric (Trastuzumab-like and Pertuzumab-like) HER2 B Cell Peptide Vaccine Emulsified in ISA 720 Adjuvant for Locally Advanced HER2 Positive Breast Cancer

This trial will test a vaccine that boosts the immune system to attack HER2-positive breast cancer in adults with locally advanced or high-risk disease.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 36 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Indiana University (Academic / other)
• Drugs / interventions: trastuzumab, trastuzmab, pertuzumab, neratinib, chemotherapy, radiation
• Locations: 1 site (Indianapolis, Indiana)
• Trial ID: NCT06949410 on ClinicalTrials.gov

What this trial studies

This Phase 1 interventional study tests an investigational HER2-targeted vaccine given to adults with high-risk or locally advanced HER2-positive breast cancer. Participants must have histologically confirmed HER2-positive tumors and meet high-risk criteria such as residual invasive disease after neoadjuvant trastuzumab-based chemotherapy, inflammatory disease, clinical stage III, or local recurrence. The primary focus in Phase 1 is to determine safety, tolerability, and whether the vaccine induces an immune response, with participants receiving the vaccine at the Indiana University Melvin & Bren Simon Comprehensive Cancer Center. Study procedures include screening, vaccine administration visits, safety monitoring, and immune response testing.

Who should consider this trial

Good fit: Adults (≥18) with histologically confirmed HER2-positive breast cancer and high-risk or locally advanced disease who can provide informed consent and travel to the Indianapolis site are ideal candidates.

Not a fit: Patients without HER2-positive tumors, those with low-risk early-stage disease, or individuals with significant immune suppression are unlikely to benefit.

Why it matters

Potential benefit: If successful, the vaccine could help the immune system control HER2-positive tumors and lower the risk of recurrence for patients with high-risk disease.

How similar studies have performed: Prior early-phase HER2-targeted vaccines have generated immune responses in some patients but have not yet delivered consistent, large-scale clinical benefit.

Eligibility criteria

Inclusion Criteria:

1. ≥ 18 years old at the time of informed consent
2. Ability to provide written informed consent and HIPAA authorization CTO-IUSCC-0864
3. Histologically confirmed HER2 positive breast cancer

   1. Any Estrogen Receptor/Progesterone Receptor status is allowed.
   2. HER2 positive is defined as HER2 3+ by immunohistochemistry (IHC) or 2+ by IHC associated with a fluorescence in situ hybridization (FISH) ratio of \> 2.0 or \> 6 total HER2 gene copies per cell.
4. High-risk disease defined as one of the following:

   1. Any residual invasive carcinoma in the breast or axillary nodes in the final pathology from resected tumor following neoadjuvant taxane and trastuzumab-based chemotherapy
   2. Inflammatory phenotype at the time of diagnosis per the treating physician
   3. Clinical stage III disease at the time of diagnosis per the treating physician and/or clinical imaging
   4. Locally recurrent disease and have undergone definitive local therapy
5. Received at least six months of HER2 targeted therapy with trastuzmab +/- pertuzumab TDM-1, or others in the neoadjuvant or adjuvant setting

   a. Any combination of HER2 targeted therapy in the curative setting is allowed, including neratinib or others on a clinical trial
6. Completed last dose of HER2 targeted therapy no more than 6 months prior to registration
7. Completed last dose of cytotoxic chemotherapy or radiation at least 30 days prior to registration with resolution of any prior toxicity to ≤ 2 with the exception of alopecia
8. ECOG performance status of 0 to 2
9. Adequate organ function as indicated by:

   1. Total bilirubin \< 1.5 mg/dL (except in patients with documented Gilbert's disease, who must have a total bilirubin \< 3.0 mg/dL)
   2. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) \< 2.0 x ULN
   3. Calculated creatinine clearance of \> 60 mL/min using the Cockcroft-Gault formula
   4. Absolute neutrophil count (ANC) \> 1.0 K/mm3
   5. Platelets \> 100 K/ mm3
10. Adequate cardiac function defined as left ventricular ejection fraction (LVEF) above the institutional lower limit of normal by echocardiogram or MUGA obtained within 90 days of registration
11. Women of childbearing potential must have a negative serum pregnancy test within 14 days of protocol registration. Women are considered to have childbearing potential (regardless of sexual orientation, having undergone a tubal ligation, or remaining celibate by choice) unless they meet one of the following criteria:

    1. Has undergone a hysterectomy or bilateral oophorectomy; or
    2. Has been naturally amenorrheic for at least 12 consecutive months.
12. Women of childbearing potential and men must agree to use one effective contraception throughout the study and for 6 months after the last study treatment.

Note: Acceptable methods of birth control include abstinence, partner with previous vasectomy, placement of an intrauterine device (IUD), condom with spermicidal foam/gel/film/cream/suppository, diaphragm or cervical vault cap, or hormonal birth control (pills or injections).

Exclusion Criteria:

1. Any distant disease recurrence.
2. Patients with active malignancy other than breast cancer. Note: Patients with prior malignancies without recurrence after standard treatment will not be excluded.
3. Patients receiving or planned to receive adjuvant CDK4/6 inhibitor therapy
4. Patients who are {MVF-HER-2(266-296) and MVF-HER-2 (597-626)} immediate hypersensitivity skin test positive.
5. Patients who require or likely to require corticosteroids or other immunosuppressives
6. Patients with active autoimmune diseases including rheumatoid arthritis, systemic lupus erythematosus, scleroderma, polymyositis dermato-myositis, or a vasculitic syndrome.

   Note: At the discretion of the treating physician, patients who show disease control for at least 6 months and do not require immunosuppressives may be enrolled.
7. Patients who have developed anaphylactic responses to other vaccines.
8. Patients who have evidence of active infection that requires antibiotic therapy. Patients must have been off antibiotic treatment for at least 3 weeks prior to initiating treatment and must be confirmed to be clear of the infection.
9. Known seropositive or active viral infection with human immunodeficiency virus (HIV), hepatitis B (HBV), or hepatitis C (HCV). Seropositivity due to vaccination are eligible.
10. Uncontrolled illness that would limit safety or compliance with study procedures including, but not limited to, active infection, congestive heart failure, unstable angina, or cardiac arrhythmia.
11. Patients with serious uncontrolled cardiopulmonary disorders, including congestive heart failure, symptomatic coronary artery disease, serious cardiac arrhythmia, and symptomatic chronic obstructive pulmonary disease or patients with other serious uncontrolled medical diseases. At the discretion of the treating physician, patients who show disease control for at least 6 months may be enrolled.
12. History of splenectomy
13. Pregnant or breast feeding.

Where this trial is running

Indianapolis, Indiana

• Indiana University Melvin & Bren Simon Comprehensive Cancer Center — Indianapolis, Indiana, United States (Recruiting)

Study contacts

• Principal investigator: Pravin Kaumaya, PhD — Indiana University
• Study coordinator: Niraj Shah

Conditions Breast Cancer; HER2-positive Breast Cancer; vaccine; immune system; immunotherapy