Dendritic Cell Vaccines against Her2/Her3 for the Treatment of Leptomeningeal Disease from Triple Negative Breast Cancer or HER2+ Breast Cancer

Inclusion Criteria

• Histologically or cytologically confirmed diagnosis of TNBC or HER2+BC per American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) guidelines (Wolff et. al. 2018). A tumor can be considered a TNBC if the estrogen receptor (ER) or progesterone receptor (PR) is < 10%
• Trial participants must have a diagnosis of LMD. They must have the presence of malignant cells in the cerebral spinal fluid (CSF) (CSF+; note now cytology is considered diagnostic of LMD if the cytology is read as positive or suspicious; (Chamberlain et al., 2017) OR characteristic radiographic abnormalities of LMD). Signs and symptoms of LMD in and of themselves are not sufficient for inclusion
• Patients must have an Eastern Cooperative Oncology Group performance scale of =< 3
• Coincident brain or spinal cord metastases are allowed if these are stable and do not require local therapy at the time of enrollment. Individuals with previously treated stable brain metastases are eligible to participate
• Stereotactic radiosurgery (SRS) and/or prior radiotherapy is permitted > 2 weeks prior to initial dendritic cell (DC) vaccine dose. A follow up brain MRI should be obtained prior to DC vaccine to determine stability of the lesions. An interval of at least 4 weeks after the end of whole brain radiation or for any surgical resection of brain lesions is permitted
• Be >= 18 years of age on the day of signing consent
• Life expectancy of >= 8 weeks
• Absolute neutrophil count >= 1500/mcL (performed with 14 days of treatment initiation)
• Platelets >= 100,000/mcL (performed with 14 days of treatment initiation)
• Hemoglobin >= 9 g/dL or >= 5.6 mmol/L (performed with 14 days of treatment initiation)
• Serum creatinine =< 1.5 X upper limit of normal (ULN) or measured/calculated creatinine clearance (CrCl) >= 60 mL/min for subject with creatinine levels > 1.5 X institutional ULN (performed with 14 days of treatment initiation) * Creatinine clearance should be calculated per institutional standard. Glomerular filtration rate can also be used in place of creatinine or CrCl
• Serum total bilirubin =< 1.5 X ULN or direct bilirubin =< ULN for patients with total bilirubin levels > 1.5 X ULN (performed with 14 days of treatment initiation)
• Asparate aminotransferase (SGOT) =< 2.5 X ULN (performed with 14 days of treatment initiation)
• Alanine aminotransferase (SGPT) =< 2.5 X ULN (performed with 14 days of treatment initiation)
• Provision of signed and dated informed consent form
• Corticosteroids at doses equivalent to 8 mg dexamethasone daily for symptom control are acceptable. This should be minimized wherever possible
• If the disease has progressed on current treatment in the central nervous system (CNS) prior to consent, patients may continue current systemic cancer therapies as per principal investigator (PI) discretion. Patients should not start a new anti-cancer agent until the 28 day safety period is completed
• Patients with systemic disease are eligible and will be managed
• Pregnancy test: negative serum or urine pregnancy test at screening for women of childbearing potential. Must be repeated once-monthly during treatment. Contraception: Highly effective contraception for both male and female subjects throughout the study and for at least 90 days after last treatment administration, if the risk of conception exists
• The patient has an Ommaya reservoir or equivalent device which allows routine access to CSF and administration of DC1s

Exclusion Criteria

• Receiving other treatments specifically administered to treat LMD within the last 2 weeks or 5 half-lives of the agent, whichever is less. However, all other treatments to control systemic disease or bulk CNS disease will be eligible, provided the therapy is not a phase I agent, an agent which significantly and unequivocally penetrates the CSF (e.g., high-dose methotrexate, thiotepa, high-dose ara-C) per PI discretion
• The use of any immunotherapy within the last four weeks
• Patients with a ventriculoperitoneal or ventriculoatrial shunt must have an on/off device in their shunt systems to be eligible for the study. Patients must be able to tolerate shunt closure for approximately 4 hours without development of clinical signs of increased intracranial pressure. Patients unable to tolerate shunt closure for approximately 4 hours will not be eligible for the study
• Unable or unwilling to have a contrast-enhanced brain MRI
• Known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or in situ cervical cancer that has undergone potentially curative therapy
• Has an active infection requiring systemic therapy which in the opinion of the investigator will increase the risk to the patient
• Had major surgical procedure, or significant traumatic injury within two weeks. Ommaya placement is allowed
• Known evidence of an intracranial thrombosis. The choice of modality is at the investigator or provider’s discretion
• Has a history of current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject’s participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator
• Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial
• Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 90 days after the last dose of trial treatment
• Has a known history of human immunodeficiency virus (HIV) (HIV 1, 2 antibodies). Testing is not mandatory
• Has known active or chronic hepatitis B (hepatitis B virus [HBV]) or hepatitis C virus (HCV). Testing is not mandatory
• Prior organ transplantation including allogenic stem-cell transplantation.
• Other severe acute or chronic medical conditions or psychiatric conditions including recent (within the past year) or active suicidal ideation or behavior; or laboratory abnormalities that may increase the risk associated with study participation or study treatment administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the patient inappropriate for entry into this study
• Has received a blood transfusion in the two weeks prior to leukapheresis
• Has received a live vaccine within 30 days prior to the first dose of study drug. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, bacillus Calmette–Guérin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (e.g., FluMist [registered trademark]) are live attenuated vaccines and are not allowed. Current coronavirus disease (COVID) vaccines are not live vaccines