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

NCT07694986 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: MCC-23481
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

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).

Conditions

Breast Cancer; Leptomeningeal Disease

Outcome Measures

Primary Outcomes (3)

• 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 Outcomes (2)

• Progression Free Survival (PFS)

  Up to 1 year

• Objective Response Rate (ORR)

  Up to 1 Year

Study Arms (3)

Safety Run-In HER2- Cohort

EXPERIMENTAL

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; Drug: Nivolumab

Safety Run-In HER2+ Cohort

EXPERIMENTAL

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; Drug: Trastuzumab

Phase 2 Efficacy Cohort

EXPERIMENTAL

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; Drug: Trastuzumab; Drug: Nivolumab

Interventions

cDC1 Vaccine BIOLOGICAL

Autologous peptide-pulsed cDC1 vaccine administered intrathecally.

Also known as: Dendritic Cell Vaccine

Phase 2 Efficacy Cohort; Safety Run-In HER2+ Cohort; Safety Run-In HER2- Cohort

Trastuzumab DRUG

150 mg intrathecal weekly for HER2-positive participants.

Phase 2 Efficacy Cohort; Safety Run-In HER2+ Cohort

Nivolumab DRUG

50 mg intrathecal every 2 weeks for HER2-negative participants.

Phase 2 Efficacy Cohort; Safety Run-In HER2- Cohort

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically or cytologically confirmed diagnosis of BC by ASCO/CAP guidelines (Wolff et al, 2018), or radiographically definite LMD from BC.
• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• H. Lee Moffitt Cancer Center and Research Institute: lead
• United States Department of Defense: collaborator

Study Sites (1)

Moffitt Cancer Center

Tampa, Florida, 33612, United States

RECRUITING

MeSH Terms

Conditions

Breast Neoplasms; Meningeal Neoplasms

Interventions

Trastuzumab; Nivolumab

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Central Nervous System Neoplasms; Nervous System Neoplasms; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Peter Forsyth, MD

  Moffitt Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Julianne Hardesty

CONTACT

813-745-4098; Julianne.Hardesty@moffitt.org

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 6, 2026
• First Posted: July 10, 2026
• Study Start: August 1, 2026
• Primary Completion (Estimated): August 1, 2029
• Study Completion (Estimated): August 1, 2030
• Last Updated: July 10, 2026

Record last verified: 2026-07

Locations

US (1)