HER2 and HER3-Directed Dendritic Cell Vaccine for the Treatment of Early Stage Triple Negative or Hormone Receptor Low Breast Cancer, The DecipHER Trial
This phase I clinical trial evaluates the best dose, safety, and effectiveness of a HER2 and HER3-directed dendritic cell vaccine prior to chemotherapy and surgery for the treatment of triple-negative or hormone receptor low breast cancer. Dendritic cells are immune cells that can signal to the immune system to fight infection. The vaccines used in this trial are made of dendritic cells that have been sensitized to HER2 and HER3 receptors, which can be found on some tumor cells. Administering these vaccines may induce an immune response against tumor cells.
Inclusion Criteria
- A diagnosis of HER2-negative breast cancer * Note: HER2- breast is defined by tumor tissue absence of HER2 overexpression and or tumor HER2 amplification. The lack of HER2 overexpression by immunohistochemistry (IHC) is defined as 0 or 1+, whereas overexpression is defined as 3+. In the event of equivocal IHC, 2+, the tumor must be gene-nonamplified by fluorescence in situ hybridization (FISH)/dual in situ hybridization (DISH) performed upon the primary tumor (ratio < 2 and HER2 copy number < 4 define HER2- disease) * Note: HER2 testing with alternative in situ hybridization chromosome-7 probe may be performed if standard IHC and FISH show equivocal results, in accordance with standard of care
- Diagnosis of HR negative or HR low positive tumor * Note: Estrogen receptor (ER) and progesterone receptor (PR) expression negativity is defined as less than 1% of tumor cells nuclei positive by immunohistochemistry in the sample on testing. HR low positive is defined as: estrogen receptor (ER) and progesterone receptor (PR) expression positivity is defined equal to or less than 20% of tumor cells nuclei positive by immunohistochemistry in the sample on testing
- Clinical stage T1c, nodal stage N1-N2 or stage T2-4, nodal stage N0-N2 breast cancer. * Note: as defined by the American Join Committee on Cancer (AJCC) TNM Stating System for Breast Cancer * Note: patients must have breast tumor able to be visualized on ultrasound and amenable to direct injection * Note: patients with bilateral synchronous breast cancer are allowed * Note: patients with recurrent tumors are allowed as long as they had not received prior treatment with paclitaxel/carboplatin (TC) followed doxorubicin hydrochloride/cyclophosphamide (AC) in the past
- Participant must be medically and surgically appropriate to undergo neoadjuvant chemotherapy regimen followed by standard of care local therapy as determined by their treating physician
- Age >= 18 years
- Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
- Absolute neutrophil count (ANC) >= 1500/uL (within 14 days of registration)
- Platelets >= 75000/uL (within 14 days of registration)
- 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 14 days of registration)
- Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 3 x institutional ULN (within 14 days of registration)
- Creatinine =< 1.5 x institutional ULN (within 14 days of registration)
- Left ventricular ejection fraction above institutional lower limit of normal (by echocardiogram or multigated acquisition [MUGA] scan)
- Female patients of childbearing potential must agree to use dual methods of contraception and have a negative serum pregnancy test at screening. 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. Effective methods of contraception must be used throughout the study and for 5 months following the last dose. To show that women do not have childbearing potential, postmenopausal women must be amenorrheic for at least 12 months naturally (and not because of/following chemotherapy) or patients must be surgically sterile
- Ability to understand and the willingness to sign a written informed consent agreement prior to study registration
Exclusion Criteria
- Patients who received prior anthracycline-based chemotherapy for the treatment of any cancer
- Patients with inflammatory breast cancer
- Patients must not be receiving any other investigational agents or active antineoplastic therapies
- 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 corticosteroid use (defined as corticosteroid use lasting one month or more)
- Female patients who are pregnant or nursing
- No other prior malignancy is allowed, except for the following: * adequately treated basal-cell or squamous-cell skin cancer, * in situ cervical cancer, * or any other cancer from which the patient has been disease free for at least 3 years
- History of testing positive for human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS)
- History of positive test for hepatitis B or hepatitis C virus indicating acute or chronic infection
- Patients who have received a live attenuated vaccine =< 30 days prior to registration
- Unable to comply with the treatment schedule and study procedures for any reason
- Previously treated with breast cancer-directed vaccine therapies in prior 3 months
- Previously treated with any form HER2- or HER3-primed DC1 therapy
Additional locations may be listed on ClinicalTrials.gov for NCT05504707.
Locations matching your search criteria
United States
Florida
Tampa
PRIMARY OBJECTIVE:
I. To determine the maximum tolerated dose (MTD) of sequential HER2- and HER3-dendritic cell (DC1) intratumoral injections for the treatment of patients with clinical stage T1c, nodal stage N1-N2 or stage T2-4, nodal stage N0-N2 triple negative or hormone receptor (HR) low positive, HER2-negative breast cancers.
SECONDARY OBJECTIVES:
I. Determine the recommended phase 2 dose (RP2D).
II. To describe the toxicity profile and dose limiting toxicities (DLTs) of HER2- and HER3-DC1 intratumoral injections in the study population.
III. To assess anti-tumor activity of sequential HER2- and HER3-DC1 intratumoral injections in the study population.
IV. To assess anti-tumor activity of alternating HER2- and HER3-DC1 intratumoral injections in the study population.
V. To assess anti-tumor activity of HER2- and HER3-DC1 intratumoral injections in the study population.
TERTIARY/EXPLORATORY OBJECTIVES:
I. To assess the correlations between cell free tumor DNA, measures of immune activation in the blood stool or tumor tissue and clinical response among study participants.
II. To assess the correlations between measures of immune activation in the blood, stool, or tumor tissue and recurrence free survival (RFS) among study participants.
OUTLINE: This is a dose escalation study followed by a dose expansion study.
Patients undergo leukapheresis prior to starting treatment and then receive ultrasound-guided alternating HER2 and HER3 dendritic cell vaccines intratumorally 3 days apart twice a week for 4 weeks in the absence of disease progression or unacceptable toxicity. Patients also undergo collection of blood and stool samples in week 1 and day 5 of week 2, magnetic resonance imaging (MRI) in weeks 5-14, and ultrasound during vaccine administration in weeks 1-4.
After completion of study treatment, patients are followed up every 6 months for 3 years.
Trial PhasePhase I
Trial Typetreatment
Lead OrganizationMoffitt Cancer Center
Principal InvestigatorRicardo Lima Barros Costa
- Primary IDMCC-20897
- Secondary IDsNCI-2022-06875
- ClinicalTrials.gov IDNCT05504707