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

Phase 2 Trial With a Safety Run-in of Combinatorial Therapies With Intrathecal (IT) Dendritic Cell Vaccines (cDC1s) inHER+ (Combined With IT Trastuzumab) and HER2- (Combined With IT Nivolumab) Breast Cancer (BC) Leptomeningeal Disease (LMD)

The purpose of this study is to learn about the effects of the study treatment, Dendritic Cell Vaccine (DCV), in combination with trastuzumab or nivolumab to confirm the highest dose of the study treatment that can be given safely to participants with Breast Cancer (BC) with Leptomeningeal Disease (LMD).

Study Overview

• Status: Recruiting
• Conditions: Breast Cancer; Leptomeningeal Disease
• Intervention / Treatment: Biological: cDC1 Vaccine; Drug: Nivolumab; Drug: Trastuzumab

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Julianne Hardesty; Phone Number: 813-745-4098; Email: Julianne.Hardesty@moffitt.org

Study Locations

• United States
  • Florida
    • Tampa, Florida, United States, 33612
      • Recruiting
      • Moffitt Cancer Center
      • Sub-Investigator: Hien Liu, MD
      • Principal Investigator: Peter Forsyth, MD
      • Sub-Investigator: Sepideh Mokhtari, MD
      • Sub-Investigator: Yolanda Pina, MD
      • Sub-Investigator: James Liu, MD
      • Sub-Investigator: Aixa Soyano Muller, MD
      • Sub-Investigator: Michael Yu, MD
      • Sub-Investigator: Hyo Han, MD
      • Sub-Investigator: Brian Czerniecki, MD
      • Sub-Investigator: Kamran Ahmed, MD
      • Sub-Investigator: Andre Beer Furlan, MD
      • Sub-Investigator: Arnold Etame, MD
      • Sub-Investigator: Joaquim Farinhas, MD
      • Sub-Investigator: Alisha Fell, ARNP
      • Sub-Investigator: Patrick Grogan, MD
      • Sub-Investigator: Nam Tran, MD
      • Sub-Investigator: Michael Vogelbaum, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Histologically or cytologically confirmed diagnosis of BC by ASCO/CAP guidelines (Wolff et al, 2018), or radiographically definite LMD from BC.
• Trial participants must have a diagnosis of LMD. They must have the presence of malignant cells in the 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 ECOG performance scale of ≤2.
• Proton cranial spinal RT OR cranial spinal RT using IMRT are the preferred modalities of RT to treat LMD if possible, before study. At least WBRT is required for participation.
• 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 before the initial dendritic cell (DC) vaccine dose. A follow-up brain MRI should be obtained before the DC vaccine to determine the stability of the lesions. An interval of at least 2 weeks after the end of brain radiation or surgical resection of brain lesions or cytotoxic, targeted, immune, or investigational agent is required.
• Must be ≥18 years of age on the day of signing the consent.
• Life expectancy of ≥8 weeks.
• Demonstrate adequate organ function as defined in Table 5. All screening labs should be performed within 14 days of treatment initiation.
• Ability to understand and the willingness to sign a written informed consent document.
• Corticosteroids at doses equivalent to ≤4 mg of dexamethasone daily or equivalent for symptom control are acceptable. This should be minimized when possible.
• If the disease has progressed on current treatment before consent, patients may continue current systemic cancer therapies by PI discretion see Section 7.7.5 (Systemic Therapies Allowed) and Section 5.2, 1 and 2 (Exclusion Criteria).
• 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.

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 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Safety Run-In HER2- Cohort; Participants with HER2-negative breast cancer leptomeningeal disease (TNBC or HR-positive) receive intrathecal HER3-pulsed cDC1 vaccines in combination with IT nivolumab.	Biological: cDC1 Vaccine; Autologous peptide-pulsed cDC1 vaccine administered intrathecally.; Other Names: Dendritic Cell Vaccine; Drug: Nivolumab; 50 mg intrathecal every 2 weeks for HER2-negative participants.
Experimental: Safety Run-In HER2+ Cohort; Participants with HER2-positive breast cancer leptomeningeal disease receive intrathecal (IT) HER2/HER3 peptide-pulsed cDC1 vaccines in combination with IT trastuzumab.	Biological: cDC1 Vaccine; Autologous peptide-pulsed cDC1 vaccine administered intrathecally.; Other Names: Dendritic Cell Vaccine; Drug: Trastuzumab; 150 mg intrathecal weekly for HER2-positive participants.
Experimental: Phase 2 Efficacy Cohort; Following completion of the safety run-in and confirmation of the RP2D, participants will receive treatment based on HER2 status: HER2-positive participants will receive IT cDC1 vaccines plus IT trastuzumab. HER2-negative participants will receive IT cDC1 vaccines plus IT nivolumab.	Biological: cDC1 Vaccine; Autologous peptide-pulsed cDC1 vaccine administered intrathecally.; Other Names: Dendritic Cell Vaccine; Drug: Nivolumab; 50 mg intrathecal every 2 weeks for HER2-negative participants.; Drug: Trastuzumab; 150 mg intrathecal weekly for HER2-positive participants.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety Run-In: Maximum Tolerated Dose (MTD)	MTD of IT cDC1s combined with IT trastuzumab for HER2+ patients or with IT nivolumab for HER2- patients.	Up to 28 days
Phase 2: Median Overall Survival	Median survival from initiation of study treatment.	Up to 1 year
Phase 2: One-Year Survival Rate	Proportion of participants alive at one year after treatment initiation.	Up to 1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression Free Survival (PFS)	Progression-free survival is defined as the time from first study treatment (Cycle 1 Day 1) until documented disease progression or death from any cause, whichever occurs first.	Up to 1 year
Objective Response Rate (ORR)	The proportion of participants achieving an objective response during study treatment. Response in leptomeningeal/CNS disease will be assessed using Response Assessment in Neuro-Oncology Leptomeningeal Metastases (RANO-LM) criteria, and response in non-CNS/systemic disease will be assessed using RECIST version 1.1 criteria.	Up to 1 Year

Collaborators and Investigators

• Sponsor: H. Lee Moffitt Cancer Center and Research Institute
• Collaborators: United States Department of Defense
• Investigators: Principal Investigator: Peter Forsyth, MD, Moffitt Cancer Center

Study record dates

Study Major Dates

• Study Start (Estimated): August 1, 2026
• Primary Completion (Estimated): August 1, 2029
• Study Completion (Estimated): August 1, 2030

Study Registration Dates

• First Submitted: July 6, 2026
• First Submitted That Met QC Criteria: July 6, 2026
• First Posted (Actual): July 10, 2026

Study Record Updates

• Last Update Posted (Actual): July 10, 2026
• Last Update Submitted That Met QC Criteria: July 6, 2026
• Last Verified: July 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nervous System Diseases; Neoplasms by Site; Neoplasms; Skin Diseases; Breast Diseases; Nervous System Neoplasms; Central Nervous System Neoplasms; Skin and Connective Tissue Diseases; Breast Neoplasms; Meningeal Neoplasms; Amino Acids, Peptides, and Proteins; Proteins; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins; Trastuzumab; Nivolumab
• Other Study ID Numbers: MCC-23481

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No