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

NCT03632941 | Active Not Recruiting Phase 2 Results DMC FDA Drug

• 1 other identifier: Pro00100093
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 1

Brief Summary

In this phase II study, participants will receive the VRP-HER2 immunizations plus pembrolizumab. 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.

Conditions

Breast Cancer; HER2+ Breast Cancer

Keywords

Cancer; Immunotherapy; PD-1 Antibody; HER2; T cell

Outcome Measures

Primary Outcomes (1)

• Number of Participants With a Positive T Cell Response Based on ELISpot Results

  The enzyme-linked immunosorbent spot (ELISpot) assay is a quantitative method that measures the frequency of cytokine secretion in a single cell.

  up to approximately 15 weeks

Secondary Outcomes (1)

• Number of Participants With a Severe Adverse Event as Assessed by CTCAE v5.0

  up to approximately 15 weeks

Other Outcomes (1)

• Number of Participants With Stable Disease as Overall Response Based on RECIST 1.1 Criteria

  up to approximately 15 weeks

Study Arms (3)

VRP-HER2 Vaccine

ACTIVE COMPARATOR

VRP-HER2 Vaccine 4 x 10EE8 IU given as a single injection every 2 weeks for 3 injections total (Cycle 1: Day 1 and Day 15 Cycle 2: Day 8)

Biological: VRP-HER2

Pembrolizumab

ACTIVE COMPARATOR

5 administrations of Pembrolizumab 200 mg every 3 weeks for 5 total IV infusions (Day 1 of each 3 week cycle x 5 cycles)

Biological: Pembrolizumab

VRP-HER2 Vaccine + Pembrolizumab

EXPERIMENTAL

VRP-HER2 Vaccine 4 x 10EE8 IU given as a single injection every 2 weeks for 3 injections total (Cycle 1: Day 1 and Day 15 Cycle 2: Day 8)+ 5 administrations of Pembrolizumab 200 mg every 3 weeks for 5 total IV infusions (Day 1 of each 3 week cycle x 5 cycles)

Biological: VRP-HER2; Biological: Pembrolizumab

Interventions

VRP-HER2 BIOLOGICAL

VRP (alphavirus-like replicon particles) containing self amplifying replicon RNA for HER2

Also known as: AVX901

VRP-HER2 Vaccine; VRP-HER2 Vaccine + Pembrolizumab

Pembrolizumab BIOLOGICAL

A humanized antibody specific for the programmed cell death 1 (PD-1) receptor.

Also known as: Keytruda

Pembrolizumab; VRP-HER2 Vaccine + Pembrolizumab

Eligibility Criteria

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

You may qualify if:

• 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 ≥100,000 / mcL Hemoglobin ≥9 g/dL or ≥5.6 mmol/L without transfusion or EPO dependency
• Serum creatinine OR Measured or calculated creatinine clearance
• 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)
• 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

You may not qualify if:

• 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.
• 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 therapy or 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.

Sponsors & Collaborators

• Herbert Lyerly: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (1)

Duke University

Durham, North Carolina, 27710, United States

Location

Related Publications (1)

• Crosby EJ, Acharya CR, Haddad AF, Rabiola CA, Lei G, Wei JP, Yang XY, Wang T, Liu CX, Wagner KU, Muller WJ, Chodosh LA, Broadwater G, Hyslop T, Shepherd JH, Hollern DP, He X, Perou CM, Chai S, Ashby BK, Vincent BG, Snyder JC, Force J, Morse MA, Lyerly HK, Hartman ZC. Stimulation of Oncogene-Specific Tumor-Infiltrating T Cells through Combined Vaccine and alphaPD-1 Enable Sustained Antitumor Responses against Established HER2 Breast Cancer. Clin Cancer Res. 2020 Sep 1;26(17):4670-4681. doi: 10.1158/1078-0432.CCR-20-0389. Epub 2020 Jul 30.

  PMID: 32732224 DERIVED

MeSH Terms

Conditions

Breast Neoplasms; Neoplasms

Interventions

pembrolizumab

Condition Hierarchy (Ancestors)

Neoplasms by Site; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Results Point of Contact

• Title: Michael Morse, M.D.
• Organization: Duke University

michael.morse@duke.edu

919-681-3480

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: August 9, 2018
• First Posted: August 16, 2018
• Study Start: March 1, 2019
• Primary Completion: October 3, 2023
• Study Completion: December 1, 2025
• Last Updated: March 12, 2025
• Results First Posted: December 11, 2024

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)