Trial of Therapies With IT cDC1s Combined w/ IT Trastuzamab for Her+ or IT Nivolumab for Her- BC LMD

Patients with systemic disease are eligible and will be managed as detailed in Section 7.7.5.

Pregnancy test: negative serum or urine pregnancy test at screening for women of childbearing potential. Must be repeated once a month during treatment.

Contraception: Highly effective contraception for both male and female subjects throughout the study, and for the following specified durations after the last treatment administration as follows: highly effective contraception must be used by males for at least 90 days after the last treatment administration, if the risk of conception exists, to cover the spermatogenesis Cycle, and at least 5 months after the last dose of nivolumab or 7 months after the last dose of trastuzumab for females.

The patient has an Ommaya reservoir or equivalent device that allows routine access to CSF and administration of DC1s.

Patient must be able to tolerate MRIs of brain with contrast for routine disease assessments.

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 that significantly and unequivocally penetrates the CSF (eg, high-dose methotrexate, thiotepa, high-dose ara-C) by PI discretion. H \& P section: Patients may continue on IV trastuzumab, fam-trastuzumab deruxtecan-nxki, pertuzumab, tucatinib, or other HER2-directed, hormonal, or other therapeutic agents if controlling systemic disease and leptomeningeal metastases developed while on these therapies. In addition, at time of systemic progression, patients may start additional agents at the discretion of the treating physician according to criteria in Section 6.7.1. and not start on new systemic therapies until LMD disease assessment.

Use of any immunotherapy within the last 4 weeks.

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 investigator's opinion will increase the risk to the patient.

Had major surgical procedure, or significant traumatic injury within 2 weeks. Ommaya placement is allowed.

Patients with shunts are excluded from the study (including but not limited to ventriculoperitoneal and ventriculoatrial shunts).

History of an intracranial thrombosis or thrombi extending up to the skull base. 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 (HBV) or hepatitis C virus (HCV). Testing is not mandatory.

ORGAN TRANSPLANTATION: 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 live vaccine within 30 days before 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 (eg, FluMist) are live attenuated vaccines and are not allowed. Current COVID vaccines are not live vaccines.

What this study is about