A Study to Evaluate Concurrent VRP-HER2 Vaccination and Pembrolizumab for Patients With Breast Cancer

  • STATUS
    Recruiting
  • End date
    Oct 26, 2022
  • participants needed
    39
  • sponsor
    Herbert Lyerly
Updated on 26 January 2021
measurable disease
metastasis
pertuzumab
HER2
trastuzumab
erbb2
mammogram

Summary

In this phase II study, study subjects will receive the VRP-HER2 immunizations plus pembrolizumab. There will be an initial Safety Arm during which subjects will receive the VRP-HER2 immunizations plus pembrolizumab. If there is no dose limiting toxicity in the Safety Arm, then subjects will be randomized into 3 arms. They will undergo a biopsy of their tumor and peripheral blood draw for immune cell analyses and be assigned to the applicable arm of the study. Arm A will consist of the the VRP-HER2 immunizations; Arm B will consist of pembrolizumab; Arm C will consist of the VRP-HER2 immunizations plus pembrolizumab.

Description

The primary objective of this phase II study is to determine whether pembrolizumab increases the tumor infiltrating and peripheral blood immune response to the VRP-HER2 vaccine. The investigators hypothesize that HER2 specific T cell responses and anti-tumor immunity induced with HER2 vaccination will be augmented by concurrent anti-PD-1 antibody therapy.

The investigators will additionally determine whether the administration of pembrolizumab is safe in patients with recurrent or metastatic HER2+ cancers who are receiving the anti-HER2 vaccine VRP-HER2.

There will be an initial Safety Arm (n=3) during which subjects will receive the VRP-HER2 immunizations plus pembrolizumab and if there is no dose limiting toxicity in the Safety Arm, subjects will then be randomized 1:1:1 into 3 arms (n=12 per arm). Subjects with metastatic HER2 overexpressing breast cancer receiving trastuzumab and pertuzumab will continue these antibodies. They will undergo a biopsy of their tumor and peripheral blood draw for immune cell analyses and be assigned to the applicable arm of the study. Arm A will consist of the the VRP-HER2 immunizations; Arm B will consist of pembrolizumab; Arm C will consist of the VRP-HER2 immunizations plus pembrolizumab. Tumor biopsies and peripheral blood draws will be performed following the course of immunizations.

Details
Condition Breast Cancer, Breast Cancer Diagnosis, HER2+ Breast Cancer, HER2+ Breast Cancer, breast carcinoma, cancer, breast, HER2+ Breast Cancer, HER2+ Breast Cancer, HER2+ Breast Cancer, HER2+ Breast Cancer
Treatment Pembrolizumab, VRP-HER2
Clinical Study IdentifierNCT03632941
SponsorHerbert Lyerly
Last Modified on26 January 2021

Eligibility

Yes No Not Sure

Inclusion Criteria

Is your age greater than or equal to 18 yrs?
Gender: Male or Female
Do you have any of these conditions: Breast Cancer or HER2+ Breast Cancer?
Do you have any of these conditions: Breast Cancer or HER2+ Breast Cancer or breast carcinoma or cancer, breast or Breast Cancer Diagnosis?
Do you have any of these conditions: Breast Cancer Diagnosis or cancer, breast or HER2+ Breast Cancer or Breast Cancer or breast carcinoma?
Do you have any of these conditions: Breast Cancer Diagnosis or breast carcinoma or cancer, breast or HER2+ Breast Cancer or Breast Cancer?
Do you have any of these conditions: Breast Cancer Diagnosis or cancer, breast or HER2+ Breast Cancer or breast carcinoma or Breast Cancer?
Have undergone treatment with trastuzumab plus pertuzumab for at least 3 weeks prior to initiation on this study
Be willing and able to provide written informed consent/assent for the trial
Resolution of all toxic side effects of prior chemotherapy, radiotherapy or surgical procedures to NCI CTCAE (version 4.03) Grade 1 (with the exception of grade 2 alopecia, grade 2 neuropathy and grade 2 fatigue)
Be >=18 years of age on day of signing informed consent
Have measurable disease based on RECIST 1.1
Be willing to provide tissue from a newly obtained core or excisional biopsy of a tumor lesion.. Subjects for whom newly-obtained samples cannot be provided may submit an archived specimen only upon agreement from the Sponsor
Have a performance status of 0 or 1 on the ECOG Performance Scale
Normal cardiac function defined as either a MUGA or ECHO with LVEF in normal institutional range
Demonstrate adequate organ function as defined below
System Laboratory Value Absolute neutrophil count (ANC) 1,500 /mcL Platelets
000 / mcL Hemoglobin 9 g/dL or 5.6 mmol/L without transfusion or EPO
dependency
Serum creatinine OR Measured or calculated creatinine clearance
5 X upper limit of normal (ULN) OR 60 mL/min for subject with creatinine levels > 1.5 X institutional ULN
Serum total bilirubin 1.5 X ULN OR Direct bilirubin ULN for subjects with
total bilirubin levels > 1.5 ULN AST (SGOT) and ALT (SGPT) 2.5 X ULN OR 5 X
ULN for subjects with liver metastases Albumin >2.5 mg/dL International
Normalized Ratio (INR) or Prothrombin Time (PT)
5 X ULN unless subject is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants
Activated Partial Thromboplastin Time (aPTT) 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 subject 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
Female subjects of childbearing potential must be willing to use an adequate method of contraception
Note: Abstinence is acceptable if this is the usual lifestyle and preferred
contraception for the subject
Male subjects of childbearing potential must agree to use an adequate method of contraception
Ability to return to Duke University Medical Center for adequate follow-up as required by this protocol

Exclusion Criteria

Patients in this study, may not receive cytotoxic chemotherapy, anti-estrogen therapy, targeted small molecule therapy, or radiation therapy in the 3 weeks before the first infusion of Pembrolizumab, during the injection period for VRP-HER2 and infusion period for Pembrolizumab or for at least 2 weeks after booster immunization with VRP-HER2 (Arm 1) or who has not recovered (i.e., Grade 1 or at baseline) from adverse events due to a previously administered agent
Has ER and or PR positive breast cancer
Patients may have received prior radiation including for brain metastases
Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Subjects with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least 3 months 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
Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapyor used an investigational device within 4 weeks of the first dose of treatment
Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment. Prior history of autoimmune thyroiditis or vitiligo is permitted
Has a known history of active TB (Bacillus Tuberculosis)
Hypersensitivity to pembrolizumab or any of its excipients
Has had a prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to study Day 1 or who has not recovered (i.e., Grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier
Has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer
Has active autoimmune disease that has required systemic treatment in the past 2 years
Has history of (non-infectious) pneumonitis that required steroids or active, non-infectious pneumonitis
Has an active infection requiring systemic therapy or systemic use of antimicrobials within 72 hours prior to the first study treatment
Has a history or 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 120 days after the last dose of trial treatment
Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent
Hypersensitivity to pembrolizumab or any of its excipients
Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies)
Has known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA is detected)
Has received a live vaccine within 30 days of planned start of study therapy
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