Dendritic Cell Vaccines Against Her2/Her3 and Pembrolizumab for the Treatment of Brain Metastasis From Triple Negative Breast Cancer or HER2+ Breast Cancer

NCT04348747 | Recruiting Phase 2 DMC FDA Drug

• 3 other identifiers: I-19-04120NCI-2020-01520W81XWH-19-0674
• Study Type: interventional
• Target: 23
• Locations: 1 country
• Sites: 3

Brief Summary

This phase IIa trial studies how well dendritic cell vaccines against Her2/Her3 and pembrolizumab work for the treatment of triple negative breast cancer or HER2+ breast cancer or HER+ Breast cancer that has spread to the brain (brain metastasis). Dendritic cell vaccines work by boosting the immune system (a system in the body that protect against infection) to recognize and destroy the cancer cells. . Pembrolizumab is an "immune checkpoint inhibitor" which is designed to either "unleash" or "enhance" the cancer immune responses that already exist by either blocking inhibitory molecules" or by activating stimulatory molecules. Giving dendritic cell vaccines and pembrolizumab may shrink the cancer.

Conditions

Anatomic Stage IV Breast Cancer AJCC v8; Metastatic Malignant Neoplasm in the Brain; Metastatic Triple-Negative Breast Carcinoma; Prognostic Stage IV Breast Cancer AJCC v8

Outcome Measures

Primary Outcomes (1)

• Central nervous system (CNS) objective response rate (ORR)

  Assessed per Response Assessment in Neuro-Oncology Brain Metastases (RANO-BM) working group. Will be summarized using frequencies and relative frequencies. A 90% confidence interval about the true ORR will be obtained using Jeffrey's prior method.

  Up to 2 years

Secondary Outcomes (10)

• Volumetric quantification of brain metastases

  Up to 2 years

• Non-CNS (i.e. of systemic disease) response rate

  Up to 2 years

• Median CNS progression free survival (PFS)

  Up to 2 years

• Non-CNS PFS

  Up to 2 years

• Overall PFS

  Up to 2 years

Other Outcomes (3)

• Changes in tumor circulating tumor lymphocyte (CTL)s

  Baseline up to 2 years

• Changes in tumor PDL-1 expression

  Baseline up to 2 years

• Changes in cytokine expression

  Baseline up to 2 years

Study Arms (1)

Treatment (anti-HER2/3 dendritic cell vaccine)

EXPERIMENTAL

TREATMENT PHASE: Patients receive anti-HER2/HER3 dendritic cell vaccine ID on days 1, 22, and 43. Patients will also receive pembrolizumab IV on the same days. MAINTENANCE PHASE: Patients receive pembrolizumab IV over 30 minutes on day 1. Cycles repeat every 21 days for 2 years in the absence of disease progression or unacceptable toxicity. Patients may also receive a booster dose of anti-HER2/3 dendritic cell vaccine ID, every 3-6 months in the opinion of principal investigator.

Biological: Anti-HER2/HER3 Dendritic Cell Vaccine; Biological: Pembrolizumab

Interventions

Anti-HER2/HER3 Dendritic Cell Vaccine BIOLOGICAL

Given ID

Also known as: Anti-HER2/3 DC Vaccine, Anti-HER2/3 Dendritic Cell Vaccine

Treatment (anti-HER2/3 dendritic cell vaccine)

Pembrolizumab BIOLOGICAL

Given IV

Also known as: Keytruda, Lambrolizumab, MK-3475, SCH 900475

Treatment (anti-HER2/3 dendritic cell vaccine)

Eligibility Criteria

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

You may qualify if:

• female participant is eligible to participate if she is not pregnant,not breastfeeding, and at least one of the following conditions applies:
• Not a woman of childbearing potential (WOCBP)
• A WOCBP who agrees to follow contraceptive guidance
• WOCBP must agree to use acceptable birth control methods for the duration of the study and until persistence of the study drug is no longer detected in the peripheral blood:this may be a period of several years. Methods for acceptable birth control include: condoms, diaphragm or cervical cap with spermicide, intrauterine device, and hormonal contraception; it is recommended that a combination of two methods be used. NOTE: If the risk of conception exists, patients must agree to use highly effective contraception throughout the study and for at least two years following the last study treatment administration
• Negative serum and highly sensitive urine pregnancy test(s):
• i) within 72 hours prior to study allocation; ii) following initiation of treatment, pregnancy testing will be performed for WOCBP and interpreted prior to every cycle of pembrolizumab (Initial Treatment Phase); iii) at the End of Treatment (EOT) Assessment; and iv) whenever pregnancy is otherwise suspected. Note: In the event that 72 hours have elapsed between the screening pregnancy test and the first dose of study treatment, another pregnancy test must be performed and must be negative in order for subject to start receiving study medication.
• Histologically or cytologically confirmed diagnosis of triple negative breast cancer (TNBC) (estrogen receptor \[ER\] =\< 1%, progesterone receptor \[PR\] =\< 1% HER2 negative) or HR+ breast cancer
• HER2 testing should be performed on the invasive component using a validated immunohistochemistry (IHC) or in situ hybridization (ISH) assay
• IHC staining is defined as:
• IHC 3+ if there is complete and intense circumferential membrane staining within \> 10 percent of tumor cells. All IHC 3+ tumors are considered HER2 positive
• IHC 2+ if there is incomplete and/or weak/moderate, circumferential membrane staining within \> 10 percent of tumor cells. All IHC 2+ tumors are reported as HER2 equivocal
• IHC 1+ if there is faint or barely perceptible, incomplete membrane staining within \> 10 percent of tumor cells. All IHC 1+ tumors are reported as HER2 negative
• IHC 0 if (1) no staining is observed, or (2) there is faint or barely perceptible, incomplete membrane staining within \< 10 percent of tumor cells. All IHC 0 tumors are reported as HER2 negative
• Equivocal HER2 testing should trigger reflex HER2 testing using ISH on the same specimen or a new test (using a different specimen with either IHC or ISH)
• Results from ISH are defined as the ratio of gene amplification of HER2 and the chromosome 17 enumeration probe (CEP17). Results are reported as:

You may not qualify if:

• Any condition which might confound the results of the study, interfere with the subject's participation for full participation (for the full duration of the study) or in the Investigator's opinion deems the participant an unsuitable candidate for the study
• Symptomatic brain metastases. Any neurologic symptoms present must have resolved with local therapy by the time of administration of study drugs
• May not be receiving any other investigational agents and may not have participated in a study of an investigational agent or using an investigational device within 4 weeks of the first dose of DC vaccine treatment
• Rapidly progressing systemic disease which might interfere with completion of all the vaccine doses
• Active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment and is allowed
• History of allogenic tissue/solid organ transplantation
• Has an active infection requiring systemic therapy which in the investigator's opinion will increase risk to the patient
• Has known active hepatitis B or hepatitis C infection (Testing is not mandatory)
• Has known immunosuppressive disease (e.g. human immunodeficiency virus \[HIV\], acquired immunodeficiency syndrome \[AIDS\] or other immune depressing disease). Testing is not mandatory
• Has received a blood transfusion in the two weeks prior to leukapheresis
• Pregnant or actively nursing (females who agree to stop nursing would be eligible) participants
• Unwilling or unable to follow protocol requirements
• Brain lesion size with significant midline shift or obstructive hydrocephalus
• The use of corticosteroids to control cerebral edema or treat neurologic symptoms will not be allowed unless at a low dose, not to exceed 10 mg of prednisone (or equivalent) per day
• History of stroke or transient ischemic attack within 6 months prior to study enrollment

Sponsors & Collaborators

• United States Department of Defense: collaborator
• Roswell Park Cancer Institute: lead

Study Sites (3)

Moffitt Cancer Center

Tampa, Florida, 33612, United States

ACTIVE NOT RECRUITING

Roswell Park Cancer Institute

Buffalo, New York, 14263, United States

RECRUITING

University of Virginia Comprehensive Cancer Center

Charlottesville, Virginia, 22903, United States

RECRUITING

MeSH Terms

Conditions

Brain Neoplasms; Triple Negative Breast Neoplasms

Interventions

pembrolizumab

Condition Hierarchy (Ancestors)

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

Study Officials

• Sheheryar Kabraji, BMBCh

  Roswell Park Cancer Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 13, 2020
• First Posted: April 16, 2020
• Study Start: December 19, 2022
• Primary Completion (Estimated): June 15, 2027
• Study Completion (Estimated): December 15, 2027
• Last Updated: February 12, 2026

Record last verified: 2026-02

Locations

US (3)