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Triple-negative Breast CancerPhase 2NSABP FB-14NCT04024800

Establishing the Recommended Biological Dose for AE37 Peptide Vaccine in Combination With Pembrolizumab That Will Enhance the Tumor-specific Immune Response and Demonstrate Efficacy in Patients With Advanced Triple-negative Breast Cancer

A Phase 2 study testing AE37 Peptide vaccine and Pembrolizumab in people with Triple-negative Breast Cancer, run by NuGenerex Immuno-Oncology at 6 sites in United States.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial summary

This study will look to establish the recommended biologic dose of AE37 in combination with pembrolizumab that will enhance the tumor-specific immune response and demonstrate efficacy in patients with advanced triple-negative breast cancer. This study will take place in two parts. Read more about this study

Who is it for?
Ages 18 years and older, women only
Conditions the study is for
Triple-negative Breast Cancer
What is being tested?
AE37 Peptide vaccine and Pembrolizumab
Could I receive a placebo?
No, everyone receives an active treatment
How many people
29 participants
Where
6 sitesUnited States
Study dates
3 May 2019to 30 Jun 2024
Phase
Phase 2
Are there results?
None posted in the registry

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

  • Have a performance status of 0 or 1 on the (Eastern Cooperative Oncology Group) ECOG Performance Scale.
  • Patients must have histologic or cytologic confirmation of the diagnosis of invasive adenocarcinoma of the breast.
  • The primary or metastatic tissue must be triple-negative (ER/PR less than or equal to 9%, HER2-negative [human epidermal growth factor receptor 2] by American Society of Clinical Oncology (ASCO)/ College of American Pathologists (CAP) guidelines).
  • There must be documentation that the patient has evidence of measurable metastatic breast cancer based on RECIST 1.1. Tumor lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions. Histologic confirmation of metastatic disease is not required.
  • At least 1 of the tumor sites must be amenable to core needle biopsy.
  • Patients with treated, stable, asymptomatic metastatic disease to the brain not requiring chronic corticosteroids are eligible (per discretion of the treating investigator).
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  • Patient must have resolution of toxic effect(s) of the most recent chemotherapy less than or equal to Grade 1 (except alopecia). If the patient has received major surgery or radiation therapy of greater than 30 Gy, they must have recovered from the toxicity and/or complication from the intervention.
  • Demonstrate adequate organ function, all screening labs should be performed within two weeks of treatment initiation.
  • ANC (absolute neutrophil count) count greater than or equal to 1,500/mm3
  • Platelets greater than or equal to 100,000/mm3
  • Hemoglobin greater than or equal to 9 g/dL
  • Creatinine less than or equal to 1.5x upper limit of normal (ULN) OR measured or calculated creatinine clearance (CrCl) greater than or equal to 30mL/min for patients with creatinine levels greater than 1.5x institutional ULN. (Glomerular filtration rate (GFR) can also be used in place of creatinine or CrCl.)
  • Total bilirubin less than or equal to 1.5x ULN OR Direct bilirubin less than or equal to ULN for patients with total bilirubin levels greater than 1.5 x ULN.
  • AST (SGOT) and ALT (SGPT) less than or equal to 2.5 x ULN OR less than or equal to 5 x ULN for patients with liver metastases.
  • A less than or equal to Grade 2 skin reaction to the first DTH inoculation is required to begin study therapy.
  • International normalized ratio (INR) or prothrombin time (PT) must be less than or equal to 1.5x ULN unless the patient is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants. Partial Thromboplastin Time (aPTT) must be less than or equal to 1.5 x ULN unless subject is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants.
  • Female patients of childbearing potential should have a negative urine or serum pregnancy within 72 hours prior to receiving the first dose of study medication. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
  • Study patients of childbearing potential must be willing to use an adequate method of contraception as outlined in the protocol or be surgically sterile, or abstain from heterosexual activity for the course of the study through 120 days after the last dose of study medication. Patients of childbearing potential are those who have not been surgically sterilized or have not been free from menses for greater than 1 year. Note: If there is any question that a participant of childbearing potential will not reliably comply with the requirements for contraception, that participant should not be entered into the study.

Who cannot join

  • Greater than 1 line of therapy for metastatic disease. Note: patients presenting with stage IV disease should have one line of standard therapy.
  • Is currently participating in or has participated in a study of an investigational agent or using an investigational device within 4 weeks of the first dose of treatment.
  • Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy (in dosing exceeding 10mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment. The use of physiologic doses of corticosteroids must be discussed with the NSABP Department of Site and Study Management (DSSM).
  • A greater than Grade 2 skin reaction to the first DTH inoculation will exclude that patient from beginning study therapy.
  • Has had a prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to study Day 1 or who has not recovered (i.e., less than or equal to Grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier.
  • Prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study Day 1 or who has not recovered (i.e., less than or equal to Grade 1 or at baseline) from adverse events due to a previously administered agent. Note: Patients with alopecia are an exception to this criterion and may qualify for the study.
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  • Blood products (including platelets or red blood cells) or administration of colony stimulating factors (including G-CSF, GM-CSF or recombinant erythropoietin) within 4 weeks prior to beginning study therapy.
  • Has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin that has undergone potentially curative therapy, or in situ cancers.
  • Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Patients with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least four weeks prior to the first dose of trial treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids for at least 7 days prior to trial treatment.
  • Has an active autoimmune disease that has required systemic treatment within the past 2 years (i.e., with use of disease modifying agents, corticosteroids, or immunosuppressive drugs). Note: Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency and bone anti-resorptive agents etc.) is not considered a form of systemic treatment.
  • Has a history of (non-infectious) pneumonitis that required steroids or current pneumonitis.
  • Has a history of or active interstitial lung disease, autoimmune lung disease, severe asthma requiring daily medication.
  • Malabsorption syndrome, ulcerative colitis, inflammatory bowel disease, resection of the stomach or small bowel, or other disease or condition significantly affecting gastrointestinal function.
  • Has an active infection requiring systemic therapy.
  • Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with a patient's participation for the full duration of the trial, or is not in the best interest of the patient 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 a child within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of trial treatment.
  • Prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-Cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) antibody (including ipilimumab or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways) is not allowed.
  • Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).
  • Has known active Hepatitis B or Hepatitis C infections or known to be positive for Hepatitis B antigen (HBsAg)/ Hepatitis B virus (HBV) DNA or Hepatitis C Antibody or RNA. Active Hepatitis C is defined by a known positive Hep C Ab result and known quantitative HCV RNA results greater than the lower limits of detection of the assay.
  • Has received a live vaccine within 30 days prior to the first dose of trial treatment. 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.
  • Note: Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (e.g., FluMist®) are live attenuated vaccines and are not allowed.
  • Has severe (greater than or equal to Grade 3) hypersensitivity to pembrolizumab and/or any of its excipients.

Trial locations and contacts

6 sites in 1 country.

6 sites in 1 country

United States6 sites

  • Cleveland Clinic

    Cleveland, Ohio, 44195

  • Stefanie Spielman Comprehensive Cancer Center

    Columbus, Ohio, 43212

  • Cancer Care Specialists of Central Illinois

    Decatur, Illinois, 62526

  • Crossroads Cancer Center

    Effingham, Illinois, 62401

  • West Virginia University

    Morgantown, West Virginia, 26506

  • Cancer Care Specialists of Central Illinois-Swansea

    Swansea, Illinois, 62226

Other trials in United States

About this study

Official title: A Phase II Clinical Trial of Pembrolizumab in Combination With the AE37 Peptide Vaccine in Patients With Metastatic Triple-Negative Breast Cancer

This study will look to establish the recommended biologic dose of AE37 in combination with pembrolizumab that will enhance the tumor-specific immune response and demonstrate efficacy in patients with advanced triple-negative breast cancer.

This study will take place in two parts. Stage 1 will be the safety cohort (13 patients) to determine the recommended dose of AE37 vaccine that can safely be administered with pembrolizumab. Stage 2 will be an expansion cohort (16 patients) that will consist of the recommended dose of AE37 determined in Stage 1.

Read the detailed description

The FB-14 is an open label, phase II study using pembrolizumab in combination with AE37 peptide vaccine (AE37) in patients with metastatic triple-negative breast cancer (mTNBC).

This study will have a Simon two-stage design. In Stage I (safety cohort), 13 patients will receive combination therapy of AE37 vaccine (without granulocyte macrophage-colony stimulating factor [GM-CSF] adjuvant) 1000 micrograms in two split intradermal injections on Day 1 of cycles 1 through 5 and pembrolizumab 200 mg intravenous infusion (IV) given Day 1 of each cycle for 2 years (1 cycle equals 21 days).

All patients (safety and expansion cohorts) will receive two delayed type hypersensitivity inoculations (DTH): the first within one week prior to beginning study therapy, which must meet the parameters of negative inoculation site assessment for eligibility as described in the protocol; and the second approximately 42 days after the last AE37 vaccine dose.

During a safety run-in, the first 3 patients will be closely followed for 6 weeks following the first dose of study therapy (2 cycles) without further accrual of patients. If one or less of the first 3 patients experience greater than or equal to Grade 3 systemic dose limiting toxicity (DLT) attributable to study therapy during the observation period, the safety run-in portion of the study will proceed with enrollment at the proposed study therapy dose (AE37 1000 micrograms and pembrolizumab 200 mg IV infusion). If there are two or more patients in the safety run-in with DLT during Cycle 1, the dose of AE37 will be decreased to dose level -1 (500 micrograms) to complete stage I accrual. The definition of a DLT is found in the protocol.

If DLT is observed during the safety run-in or in greater than 25% (4 or more) of patients in stage I, the AE37 dose will be de-escalated to 500 micrograms (dose level -1) for all patients to complete stage I accrual. If systemic toxicity occurs in greater than or equal to 3 patients at dose level -1, accrual will be halted and the toxicity reviewed by the study team.

Being tested
AE37 Peptide vaccine, Pembrolizumab
Keywords
Triple-negative Breast Cancer, Tumor-specific immune response, Open-Label, Pembrolizumab, Peptide vaccine, Metastatic Breast Cancer, Dose limiting toxicity, RECIST 1.1, AE37
Medical subject headings
Triple Negative Breast Neoplasms, Breast Neoplasms

What participants receive

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

  • AE37 Peptide vaccineBiological

    Also called AE37

    Starting dose: AE37 vaccine 1000 micrograms split into 2 doses given as intradermal injection on day 1 of every 3 week cycle (21 day cycle) for 5 cycles.

    Should ≥ grade 3 systemic toxicities (DLT) occur in > 25% (4) of the first 13 patients (4 or more) the study therapy vaccine dose will be de-escalated to 500 micrograms (dose level -1).

  • PembrolizumabBiological

    Also called MK-3475

    Pembrolizumab 200 mg IV on day 1 of every 3 week cycle (21 day cycle) for 2 years (35 cycles)

Study groups in NCT04024800
Study groupRoleWhat they receive
Arm 1ExperimentalAE37 peptide vaccine every 21 days for 5 doses + Pembrolizumab every 21 days for 2 years (Maximum 35 cycles)
Receives: Biological: AE37 Peptide vaccine; Biological: Pembrolizumab

What is being measured

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

  1. Recommended dose

    Recommended dose of AE37 that can be safely administered with pembrolizumab. If dose limiting toxicities occur in 4 of the first 13 patients the study therapy vaccine dose will be de-escalated to 500 micrograms (dose-level 1). If fewer than 4 patients experience DLTs then the expansion cohort of 16 patients will be added.

    Measured: Day 1, within 72 hours of vaccination (48-72 hours), and as adverse events occur in each cycle (21 days) of study therapy (first 13 patients).

  2. Objective response rate

    Objective response rate determined by RECIST 1.1 with modifications for progressive disease confirmation

    Measured: From study entry through disease progression or intolerable toxicity for a maximum of 35 cycles (21 days cycle) )or two years.

Secondary outcomes (4)

  1. Progression-free Survival

    Progression-free survival with pembrolizumab in combination with AE37

    Measured: From study entry through disease progression or intolerable toxicity for a maximum of 35 cycles (21 days cycle) or two years.

  2. Overall Survival

    Overall survival rate at 1 year from start of therapy.

    Measured: From study entry through disease progression or intolerable toxicity for a maximum of 35 cycles (21 days cycle) or two years.

  3. Clinical benefit rate

    Clinical benefit rate as measured by disease status by continuous tumor measurement

    Measured: From study entry through disease progression or intolerable toxicity for a maximum of 35 cycles (21 days cycle) or two years.

  4. Overall Toxicity

    Adverse events experienced by participants receiving AE37 in combination with pembrolizumab as a measure of toxicity

    Measured: Adverse events assessed from the beginning of study therapy through 90 days after the last dose of study therapy

Timeline

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

  1. First posted18 Jul 2019
  2. Study start3 May 2019
  3. Primary completion30 Jun 2023 (estimated)
  4. Study completion30 Jun 2024 (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
29 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04024800
Sponsor's protocol ID
NSABP FB-14
Other IDs
MK3475 KN 548
Acronym
NSABP FB-14
Status last verified
May 2021
First submitted
25 Jun 2019
Last updated
2 Jun 2021
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing AE37 Peptide vaccine and Pembrolizumab in people with Triple-negative Breast Cancer, run by NuGenerex Immuno-Oncology at 6 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 18 inclusion and 23 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: status not confirmed, as of the sponsor's last update on 2 Jun 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 6 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?

Results are not available in the source record.

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

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Recommended dose (time frame: Day 1, within 72 hours of vaccination (48-72 hours), and as adverse events occur in each cycle (21 days) of study therapy (first 13 patients).). The study lists 2 primary outcomes in all. 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 NCT04024800.

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 2 Jun 2021.

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