Adoptive T Cell Therapy with Dendritic Cell Vaccine for HER2-positive Breast Cancer

Phase 1 Study of Adoptive T Cell Therapy Following HER2-Pulsed Dendritic Cell Vaccine and Pepinemab / Trastuzumab in Patients With Metastatic HER2-Positive Breast Cancer

This study is testing a new treatment that combines a special vaccine and immune cells to see if it can help people with HER2-positive metastatic breast cancer feel better.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 28 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: H. Lee Moffitt Cancer Center and Research Institute (Academic / other)
• Drugs / interventions: trastuzumab, chemotherapy, pepinemab, cyclophosphamide
• Locations: 1 site (Tampa, Florida)
• Trial ID: NCT05378464 on ClinicalTrials.gov

What this trial studies

This study aims to evaluate the safety of adoptive T-cell therapy following a dendritic cell vaccine in combination with pepinemab and trastuzumab for patients with HER2-positive metastatic breast cancer. Participants will receive six weekly injections of dendritic cell vaccines alongside standard care with trastuzumab and pepinemab. The approach involves expanding HER2-specific T cells ex vivo, which will then be infused into patients after lymphodepletion therapy. The study seeks to enhance the immune response against HER2-positive cancer cells.

Who should consider this trial

Good fit: Ideal candidates include patients with histologically confirmed HER2-positive metastatic breast cancer who have experienced disease progression on trastuzumab and have received no more than three lines of cytotoxic chemotherapy.

Not a fit: Patients who do not have HER2-positive breast cancer or those who have not progressed on trastuzumab may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a novel immunotherapy option that enhances the immune response against HER2-positive breast cancer.

How similar studies have performed: Other studies have shown promising results with similar immunotherapeutic approaches, suggesting potential for success in this novel combination.

Eligibility criteria

Inclusion Criteria:

* Must have a histologically confirmed HER2 positive breast cancer and must be candidates for trastuzumab therapy as per current standard of care. Note: HER2 positive breast cancer is defined by tumor tissue HER2 overexpression and or tumor HER2 amplification per ASCO/CAP criteria.
* Patients will be eligible regardless of ER/PR status which will be determined per 2020 ASCO/CAP guideline and hormonal therapy will be allowed to continue for patients with ER/PR positive disease.
* Must have evaluable disease, defined as at least one lesion that can be accurately measured ≥ 10 mm by standard imaging techniques that can be include but not limited to CT, PET, PET/CT, MRI. Skeletal disease which is measurable by PET/CT or bone scan will also be allowed.
* Must have had disease progression while on trastuzumab for the treatment of HER2+ MBC and received no more than 3 lines of cytotoxic chemotherapy in the setting of metastatic disease.
* ECOG performance status 0 or 1.
* Must have normal organ and marrow function as defined in protocol within 14 days of registration.
* Left ventricular ejection fraction above institutional lower limit of normal (by echocardiogram or MUGA scan)
* Female patients of childbearing potential must agree to use dual methods of contraception and have a negative serum or 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 3 months following the last dose. To be considered of not to be of childbearing potential, postmenopausal women must be amenorrheic for at least 12 months naturally (not in the setting of post chemotherapy) or patients must be surgically sterile.
* Must have the ability to understand and the willingness to sign a written informed consent prior to registration on study.
* Must have a life expectancy of at least 12 weeks.

Exclusion Criteria:

* Patients who have had chemotherapy or radiotherapy within 14 days prior to beginning protocol therapy.
* Patients may not be receiving any other investigational agents within 14 days or 5 half-lives (whichever is longer) prior to beginning protocol therapy.
* Patients with uncontrolled brain metastases or leptomeningeal disease
* Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
* Patients with active autoimmune disease or history of autoimmune disease that might recur, which may affect vital organ function or require immune suppressive treatment including chronic prolonged systemic corticosteroids (defined as corticosteroid use of duration one month or greater), should be excluded.
* Female patients who are pregnant or nursing are not eligible.
* Second invasive malignancy requiring active treatment
* Known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS) is not permitted.
* Any known positive test for Hepatitis B or Hepatitis C virus indicating acute or chronic infection is not permitted.
* Patients who have received a live attenuated vaccine ≤30 days of registration are not eligible.
* Patients not able to comply with the treatment schedule and study procedures for any reason are not eligible.
* Patients previously treated with any form of adoptive cell transfer therapy.

Where this trial is running

Tampa, Florida

• Moffitt Cancer Center — Tampa, Florida, United States (Recruiting)

Study contacts

• Principal investigator: Heather Han, MD — Moffitt Cancer Center
• Study coordinator: Kim Sprenger

Conditions HER2-positive Breast Cancer; Breast Cancer; T-Cell therapy