Concurrent VRP-HER2 Vaccination and Pembrolizumab for Patients With Breast Cancer
Enabling precision immunity by vaccination against a tumor oncogene in combination with PD-1 blockade
Phase I trial of HER2 vaccine supporting this Phase II trial
Impact of HER2 vaccination alone in HER2+ metastatic cancer patients
In a past-clinical trial, we found that our synthetic replicating RNA vaccine against HER2 could elicit striking HER2-specific immunity in mice and that its use as a solo agent in patients (in a Phase I trial) was safe and could elicit HER2-specific memory T-cell responses that associated with enhanced progression free survival.  This successful trial motivated our search for agents that would improve T-cell functionality in tumors.
Description of Cancer Vaccines
Pre-clinical Studies supporting the Phase II approach
Using HER2 vaccination + PD-1 antibodies significantly enhanced anti-tumor responses in mice
Using advanced animal models of HER2+ Breast Cancer, we tested the impact of HER2 vaccination in combination with anti-PD-1 mAbs. While HER2 vaccines could elicit HER2-specific T-cell, the use of PD-1 mAbs allowed these T-cells to function and kill tumor cells more effectively in the tumor microenvironment without becoming exhausted, leading to a significant survival advantage.
Trial Specifics
Rationale, Entry Criteria and Design
Trial Design
Trial Schema
The study started with an initial Safety Arm of 3 patients and is now in the randomization phase for subjects with metastatic HER2-overexpressing breast cancer receiving trastuzumab and pertuzumab. They will undergo a biopsy of their tumor and peripheral blood draw for immune cell analyses and be assigned randomly to Arm A which will consist of the VRP-HER2 immunizations or Arm B which will consist of pembrolizumab or Arm C which will consist of the VRP-HER2 immunizations plus pembrolizumab. Tumor biopsies and peripheral blood draws will be performed following the course of immunizations.
Detailed information regarding the specific treatment schedule is viewable at the link below.
Entry Criteria
Who is eligible?
-This Phase II clinical study is restricted to patients with locally recurrent or metastatic HER2+ Breast Cancer (of any positive type).
This trial is open to patients who are hormone receptor positive or negative.
-Patients on this trial must have undergone treatment with Trastuzumab and pertuzumab for at least three weeks prior to enrollment in this study
-Patients on this study may continue to receive HER2 mAb therapies and endocrine targeted therapies.Â
-Detailed eligibility criteria are viewable at the link below
Trial Risks
Possible Side Effects
Because this is the first time AVX901 in combination with Pembrolizumab has been given to humans, there may be risks, discomforts, drug interactions or side effects that are not yet known.Â
Based on our previous Phase I trial, there are several possible side effects, as with the FDA approved use of Pembrolizumab. These possible side effects and risks are details in the link below.