Final report on Phase I/II trial of E75 her2 bc vaccine
 

Ann Oncol. 2014 Jun 6. pii: mdu211. [Epub ahead of print]
Final Report of the Phase I/II Clinical Trial of the E75 (nelipepimut-S) Vaccine with Booster Inoculations to Prevent Disease Recurrence in High-Risk Breast Cancer Patients.
Mittendorf EA1, Clifton GT2, Holmes JP3, Schneble E4, van Echo D5, Ponniah S6, Peoples GE7.
Author information

Abstract
BACKGROUND:
E75 (nelipepimut-S) is a human leukocyte antigen (HLA)-A2/A3-restricted immunogenic peptide derived from the HER2 protein. We have conducted phase I/II clinical trials vaccinating breast cancer patients with nelipepimut-S and GM-CSF in the adjuvant setting to prevent disease recurrence. All patients have completed 60 months follow-up, and here, we report the final analyses.
PATIENTS AND METHODS:
The studies were conducted as dose escalation/schedule optimization trials enrolling node-positive and high-risk node-negative patients with tumors expressing any degree of HER2 (immunohistochemistry 1-3+). HLA-A2/3+ patients were vaccinated; others were followed prospectively as controls. Local and systemic toxicity was monitored. Clinical recurrences were documented, and disease-free survival (DFS) was analyzed by Kaplan-Meier curves; groups were compared using log-rank tests.
RESULTS:
Of 195 enrolled patients, 187 were evaluable: 108 (57.8%) in the vaccinated group (VG) and 79 (42.2%) in the control group (CG). The groups were well-matched for clinicopathologic characteristics. Toxicities were minimal. Five-year DFS was 89.7% in the VG versus 80.2% in the CG (P=.08). Due to trial design, 65% of patients received less than the optimal vaccine dose. Five-year DFS was 94.6% in optimally dosed patients (P=.05 versus the CG) and 87.1% in suboptimally dosed patients. A voluntary booster program was initiated, and among the 21 patients that were optimally boosted, there was only one recurrence (DFS=95.2%).
CONCLUSION:
The E75 vaccine is safe and appears to have clinical efficacy. A phase III trial evaluating the optimal dose and including booster inoculations has been initiated.
CLINICAL TRIALS:
NCT00841399, NCT00584789.
© The Author 2014. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.
KEYWORDS:
Breast cancer; immunotherapy; nelipepimut-S; vaccine

PMID: 24907636 [

Re: Final report on Phase I/II trial of E75 her2 bc vaccine
 

Lani,

Thanks for this post. I'm glad to hear that some vaccine trials for breast cancer are in phase III.

I recently asked my oncologist why we don't see more phase III vaccine trials. It's as if they never make it to that phase. He said that's because they only "tickle" the immune system in breast cancer patients. Not much more than that.

I've been approached a few times about participating in a HER2+ vaccine trial and had been discussing that option with my oncologist.

Last year, I became more interested in immunotherapy for breast cancer after seeing the PD-L1 session at ASCO. However, I also learned there at a meeting for advocates that some cancers are more amenable to immunotherapy, such as melanoma, and that breast cancer isn't. That perhaps melanoma and some other cancers have more immune receptors (for lack of a better way to describe it) than breast cancer? But that doesn't mean that scientists shouldn't keep trying.

Re: Final report on Phase I/II trial of E75 her2 bc vaccine
 

The Phase II for we Her2 3+ individuals will start this year. The current Phase III is for Her2 1+ and 2+, the PRESENT study.

Typically adjuvant vaccines require enrollment into the trial within 6 months of completing Herceptin.