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Anatomic Stage IV Breast Cancer AJCC v8Phase 2NCT04348747

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

A Phase 2 study testing Anti-HER2/HER3 Dendritic Cell Vaccine and Pembrolizumab in people with Anatomic Stage IV Breast Cancer AJCC v8 and Metastatic Malignant Neoplasm in the Brain, run by Roswell Park Cancer Institute at 3 sites in United States.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
Search all trials

Trial 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). Read more about this study

Who is it for?
Ages 18 years and older, women only
What is being tested?
Anti-HER2/HER3 Dendritic Cell Vaccine and Pembrolizumab
Could I receive a placebo?
No, everyone receives an active treatment
How many people
23 participants
Where
3 sitesUnited States
Study dates
19 Dec 2022to 15 May 2028
Phase
Phase 2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • Women only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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):
  • At initial screening prior to eligibility confirmation
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  • within 72 hours prior to leukapheresis if >72 hours have passed between screening test and the Leukapheresis visit
  • Pregnancy testing will be performed for WOCBP and interpreted prior to every cycle of pembrolizumab (Initial Treatment Phase);
  • at the End of Treatment (EOT) Assessment; and
  • whenever pregnancy is otherwise suspected. Note: In the event that 72 hours have elapsed between the screening pregnancy test and leukapheresis, another pregnancy test must be performed and must be negative in order for subject to undergo leukapheresis
  • 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:
  • ISH positive if the HER2/CEP17 ratio is >= 2.0, and the HER2 copy number signals/cell is >= 4
  • Definitive diagnosis will be rendered pending further workup in the following instances:
  • If the HER2/CEP17 ratio is >= 2.0 and an average HER2 copy number is < 4.0 signals/cell - negative if confirmed on retesting
  • If the HER2/CEP17 ratio is < 2.0 and the average HER2 copy number is >= 6.0 signals/cell positive - if confirmed on retesting
  • If the HER2/CEP17 ratio is < 2.0 and an average HER2 copy number is between >= 4.0 and < 6.0 signals/cell negative - if confirmed on retesting
  • ISH negative if the HER2/CEP17 ratio is < 2.0 and average HER2 copy number is < 4.0 signals/cell
  • Measurable brain disease as per RANO-BM criteria modified to include the cut off point of 0.5 cm or higher. Have at least one untreated (includes irradiation) brain metastasis approved by a research team that meets the following size requirements:
  • >= 0.5 cm AND twice the magnetic resonance imaging (MRI) slice thickness; and
  • < 3.0 cm, that is asymptomatic and does not require local therapy at the time of enrollment (i.e. target lesion[s])
  • Of note, lesions >= 0.5 cm and < 3 cm may be determined ineligible by the research team because of location or symptoms. An untreated brain metastasis is defined as a lesion not present at the time of whole brain radiation therapy or not included in a stereotactic radiotherapy field (or within 0.5 cm of a treated lesion), or any lesion that is new or unequivocally progressing since prior radiation therapy or prior surgery.
  • Any brain metastasis >= 3.0 cm or causing symptoms must have previously been treated with local therapy (i.e. radiation or surgical resection, as clinically appropriate) prior to study enrollment. Any lesion present at the time of whole brain radiation therapy (WBRT) or included in the stereotactic radiotherapy field (or within 5 mm of the treated lesion) will NOT be considered evaluable unless it is new or documented to have progressed since treatment
  • Stereotactic radiosurgery (SRS) and/or prior radiotherapy is permitted >=2 weeks prior to initial Dendritic Cell (DC) vaccine dose (leaving one or more lesions which are not radiated and will be used as target lesions) but a follow up brain MRI should be obtained prior to dendritic cell (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 ; an interval of at least 4 weeks or 5 half-lives (whichever is sorter) after the last cytotoxic, targeted, immunotherapeutic or investigational agent is permitted (prior to the start of DC vaccine)
  • Previous whole brain radiation is allowed if patient has been diagnosed with recurrent, progressive brain metastasis. Previously irradiated lesions would be considered non-target lesions
  • Previously resected lesions or those treated with SRS would be considered nontarget lesions. There is no limitation on prior local therapies to other lesions.
  • If subject received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
  • Toxicity that has not recovered to <=Grade 1 is allowed if it meets the inclusion requirments for lab parameters (Participants with <= Grade 2 neuropathy may be eligible)
  • Patients must have adequate organ and marrow function as defined below (specimens must be collected within 10 days prior to the start of study treatment):
  • Hemoglobin >= 9 g/dL or >= 5.6 mmol/L
  • Leukocytes: >= 3 x 10^9/L
  • Absolute neutrophil count: >= 1.5 x 10^9/L
  • Platelets: >= 100 x 10^9/L
  • Total bilirubin: =< 1.5 x upper limit of normal (ULN) OR direct bilirubin =< ULN for participants with total bilirubin levels > 1.5 x ULN
  • Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]): =< 2.5 x institutional upper limit of normal (=< 5 x ULN for participants with liver metastases)
  • Creatinine OR Measured or calculated creatinine clearance (Glomerular Filtration Rate (GFR) can also be used in place of creatinine or CrCl): ≤1.5 × ULN OR ≥30 mL/min for participant with creatinine levels >1.5 × institutional ULN
  • International normalized ratio (INR) OR prothrombin time (PT) activated partial thromboplastin time (APTT) =< 1.5 x ULN unless participant is receiving anticoagulant therapy as long as PT or aPTT is within therapeutic range of intended use of anticoagulants
  • No evidence of leptomeningeal disease
  • If patient is on steroids, they must be on a steroid dose less than or = to an equivalent prednisone dose of 10 mg daily
  • Life expectancy of > 3 months
  • Prior checkpoint inhibitors permitted 3 weeks prior to enrollment
  • If the disease has progressed on current treatment in the CNS, prior to consent, patients may continue Her 2 directed antibody treatment (trastuzumab and pertuzumab); aromatase inhibitor or tamoxifen while on the study; patients with triple negative breast cancer may continue capecitabine, eribulin or paclitaxel while on study per PI discretion
  • Patients with systemic disease will be managed as detailed in Section 10.1 - Patients who develop systemic disease progression on the protocol will be managed as detailed in Section 10.4.2

Who cannot join

  • 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
  • Has had prior chemotherapy or targeted small molecule therapy (except treatment mentioned in inclusion criteria 17) within 4 weeks or 5 half-lives (whichever is sooner) prior to start of treatment (first DC vaccine) or who has not recovered (i.e., =< grade 1 or at baseline) from adverse events due to a previously administered agent. Previous radiation to extracranial sites may be completed at any time prior to initiation of study drugs (first DC vaccine) with a 2-week washout is required.
  • 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
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  • 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
  • History of (non-infectious) pneumonitis /interstitial lung disease that required steroids, or has current pneumonitis/ interstitial lung disease
  • Presence of leptomeningeal disease
  • Any contraindication to MRI (i.e., patients with pacemakers or other metal implanted medical devices). An MRI safety questionnaire is required prior to MR imaging
  • Has received prior radiotherapy within 2 weeks of start of study treatment with dendritic cell (DC) vaccine and/or has received SRS <2. weeks prior to the administration of the first DC vaccine dose. Participants must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted for palliative radiation (=< 2 weeks of radiotherapy) to non-CNS disease
  • Has received a live vaccine or live-attenuated vaccine within 30 days prior to the first dose of study drug. Seasonal influenza vaccines for injection are allowed; however, intranasal influenza vaccines (e.g., FluMist) are live attenuated vaccines and are not allowed. Administration of killed vaccines is allowed.
  • Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug (DC vaccine)
  • Has a known additional malignancy that is progressing or has required active treatment within the past 3 years. Note: Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ (e.g. breast carcinoma, cervical cancer in situ) that have undergone potentially curative therapy are not excluded
  • A WOCBP who has a positive urine or blood pregnancy test at screening and within 72 hrs prior to leukapheresis
  • Note: in the event that 72 hrs have elapsed between the initial screening pregnancy test and leukapheresis, another pregnancy test (urine or serum) must be performed and must be negative in order for subject to undergo leukapheresis
  • Known active carcinomatous meningitis
  • Known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.

Trial locations and contacts

3 sites in 1 country. Contact the study team or a site near you to ask about taking part.

United States3 sites, 2 recruiting

  • Roswell Park Cancer Institute

    Buffalo, New York, 14263

    Sheheryar Kabraji, BMBCh, 716-845-1486, Sheheryar.Kabraji@roswellpark.org

    Sheheryar Kabraji

    Recruiting

  • University of Virginia Comprehensive Cancer Center

    Charlottesville, Virginia, 22903

    Patrick Dillon, MD, 434-924-8073, PMD5B@uvahealth.org

    Patrick Dillon, MD

    Recruiting

  • Moffitt Cancer Center

    Tampa, Florida, 33612

    Active, not recruiting

Other trials in United States

About this study

Official title: A Phase IIa Study of Dendritic Cell Vaccines Against Her2/Her3 and Pembrolizumab in Patients With Asymptomatic Brain Metastasis From Triple Negative Breast Cancer (TNBC) or HER2+ Breast Cancer (HER2+BC) or Hormone Receptor Positive (HR+) Breast Cancer.

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.

Read the detailed description

PRIMARY OBJECTIVE:

  • I. The best overall central nervous system (CNS) response as per Response Assessment in Neuro-Oncology Brain Metastases (RANO-BM).

SECONDARY OBJECTIVES:

  • I. Volumetric quantification of brain metastases.
  • II. The non-CNS (i.e. of systemic disease) response rate as per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1.
  • III. The median CNS, non-CNS and overall progression free survival (PFS).
  • IV. The median overall survival (OS).
  • V. The safety of this regimen.
  • VI. The proportion of patients not requiring retreatment for their brain metastasis at 6 months since the first dose of anti-HER2/3 vaccine.
  • VII. Rate of failure of irradiated lesions.

OUTLINE:

TREATMENT PHASE: Patients receive anti-HER2/HER3 dendritic cell vaccine intradermally (ID) on days 1, 22, and 43. Patients also receive Pembrolizumab intravenous (IV) infusion on the same day.

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/HER3 dendritic cell vaccine ID, every 3-6 months in the opinion of principal investigator.

Being tested
Anti-HER2/HER3 Dendritic Cell Vaccine, Pembrolizumab
Medical subject headings
Brain Neoplasms, Triple Negative Breast Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Anti-HER2/HER3 Dendritic Cell VaccineBiological

    Also called Anti-HER2/3 DC Vaccine, Anti-HER2/3 Dendritic Cell Vaccine

    Given ID

  • PembrolizumabBiological

    Also called Keytruda, Lambrolizumab, MK-3475, SCH 900475

    Given IV

Study groups in NCT04348747
Study groupRoleWhat they receive
Treatment (anti-HER2/3 dendritic cell vaccine)ExperimentalTREATMENT 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.
Receives: Biological: Anti-HER2/HER3 Dendritic Cell Vaccine; Biological: Pembrolizumab

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: Within 6 months of treatment start date

Secondary outcomes (10)

  1. Volumetric quantification of brain metastases

    Measured: Up to 2 years

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

    Assessed per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1.

    Measured: Up to 2 years

  3. Median CNS progression free survival (PFS)

    Will be summarized using frequencies and relative frequencies. A 90% confidence interval about the true response rate will be obtained using Jeffrey's prior method.

    Measured: Up to 2 years

  4. Non-CNS PFS

    Will be summarized using frequencies and relative frequencies. A 90% confidence interval about the true response rate will be obtained using Jeffrey's prior method.

    Measured: Up to 2 years

  5. Overall PFS

    Will be summarized using frequencies and relative frequencies. A 90% confidence interval about the true response rate will be obtained using Jeffrey's prior method.

    Measured: Up to 2 years

  6. Proportion of patients who have a CNS PFS

    Measured: At 6 months

  7. Median overall survival (OS)

    Measured: Up to 2 years

  8. Incidence of adverse events

    Safety of the regimen characterized by type, frequency, severity (according to Common Terminology Criteria for Adverse Events [CTCAE] version 5.0), timing, seriousness and relationship to study treatment. All toxicities and adverse events will be summarized by grade using frequencies and relative frequencies.

    Measured: Up to 2 years

  9. Proportion of patients not requiring retreatment for their brain metastasis at 6 months since the first dose of anti-HER2/3 vaccine

    Will be summarized using standard Kaplan-Meier methods. Estimates of the median time and 6-month rates will be obtained with 90% confidence intervals.

    Measured: At 6 months

  10. Rate of failure of irradiated lesions

    Measured: Up to 2 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted16 Apr 2020
  2. Study start19 Dec 2022
  3. Primary completion15 May 2028 (estimated)
  4. Study completion15 May 2028 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
23 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04348747
Sponsor's protocol ID
I-19-04120
Other IDs
NCI-2020-01520, I-19-04120, W81XWH-19-0674
Status last verified
Jul 2026
First submitted
13 Apr 2020
Last updated
21 Jul 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Anti-HER2/HER3 Dendritic Cell Vaccine and Pembrolizumab in people with Anatomic Stage IV Breast Cancer AJCC v8 and Metastatic Malignant Neoplasm in the Brain, run by Roswell Park Cancer Institute at 3 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 51 inclusion and 27 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 21 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Each site lists its own contact: choose the nearest one under Trial locations. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Central nervous system (CNS) objective response rate (ORR) (time frame: Within 6 months of treatment start date). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04348747.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Jul 2026.

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