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

[Lani]

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 [

[Joan M]

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.

['lizbeth]

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.

Apr 28, 2014

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Galena Biopharma Announces Department of Defense Grant for NeuVax(TM) (nelipepimut-S) Clinical Trial

• Phase 2 study in neoadjuvant, HER2 3+ Breast Cancer Patients to commence in 2014
• New study supports ongoing Phase 3 PRESENT study and Phase 2b in HER2 1+ and 2+ patients

PORTLAND, Ore., April 28, 2014 (GLOBE NEWSWIRE) -- Galena Biopharma (Nasdaq:GALE), a biopharmaceutical company developing and commercializing innovative, targeted oncology treatments that address major unmet medical needs to advance cancer care, today announced the Department of Defense (DoD) will provide funding towards a new clinical trial with NeuVax to prevent breast cancer recurrence in high-risk HER2 3+ patients. The grant, a Breast Cancer Research Program (BCRP) Breakthrough Award, was obtained by Elizabeth A. Mittendorf, M.D., Associate Professor, Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center who will oversee the investigator-sponsored trial. Galena will support the trial with study drug and funding and will have access to the research to support ongoing registrational studies.
"Receipt of this grant from the Department of Defense for a new clinical trial is a significant validation of the potential utility of NeuVax in a variety of cancer settings," said Mark J. Ahn, Ph.D., President and Chief Executive Officer of Galena Biopharma. "This trial significantly expands the breast cancer patient population for NeuVax, adding women who are HER2 3+ to our ongoing trials in the HER2 1+ and 2+ patients. We are excited to work with Dr. Mittendorf and her team to advance this trial that is expected to initiate in the second half of 2014."
The protocol for the multi-center, prospective, randomized, single-blinded Phase 2 trial is being finalized and is expected to enroll approximately 100 patients with a diagnosis of HER2 3+ breast cancer who are HLA A2+ or HLA A3+ and are determined to be at high-risk for recurrence. High-risk is defined as having received neoadjuvant therapy with an approved regimen that includes trastuzumab but not obtaining a pathological complete response at surgery, or those who undergo surgery as a first intervention and are found to be pathologically node-positive. These high-risk patients are known to have higher recurrence rates than other HER2 3+ breast cancer patients. Eligible patients will be randomized to receive NeuVax + GM-CSF (granulocyte macrophage-colony stimulating factor) + trastuzumab or trastuzumab + GM-CSF alone. The primary endpoint of the study is disease-free survival.
"Based on other encouraging studies using NeuVax and Herceptin in other treatment settings, this study explores this promising combination approach of complimentary targeted agents in clinically high-risk HER2 3+, or positive, patients," added Dr. Mittendorf.
The grant was awarded through the Congressionally Directed Medical Research Program (CDMRP), funded through the Department of Defense (DoD), via annual Congressional legislation known as the Defense Appropriations Act.