Interim Analysis of a Randomized Phase II Study of the Novel Ii-Key Hybrid HER2/<i>Neu</i> Peptide (AE37) Vaccine To Prevent Breast Cancer Recurrence: United States Military Cancer Institute Clinical Trials Group Study I-05.
Authors: G. Peoples, S. Perez, G. Clifton, J. Holmes, K. Georgakopoulou, L. Benavides, J. Gates, E. von Hofe, C. Baxevanis, E. Mittendorf, A. Ardavanis, S. Ponniah, M. Papamichail
Journal: Cancer Research (2009)

Abstract BACKGROUND: CD4+ T helper peptides from HER2/neu have been evaluated in vaccine trials. The Ii-Key addition, a 4-amino-acid (LRMK) modification, increases vaccine potency when compared to unmodified class II epitopes. We present results of a prospective, randomized, single-blinded phase II clinical trial of the Ii-Key hybrid HER2/neu peptide (AE37) + GM-CSF immunoadjuvant vaccine versus GM-CSF alone in the adjuvant setting in disease-free, high risk breast cancer (BCa) patients to prevent recurrence.METHODS: Disease-free, high risk BCa patients who have completed standard adjuvant therapy were enrolled and randomized to receive six monthly inoculations of either 500 mcg of AE37 with 62.5 or 125 mcg of GM-CSF (Peptide group; PG) or 62.5 or 125 mcg of GM-CSF alone (adjuvant group; AG). Toxicity was assessed after each inoculation using National Cancer Institute Common Terminology Criteria for Adverse Events v3.0 (CTCAE). Immunologic response was monitored using delayed type hypersensitivity reactions (DTH) and 3H-thymidine proliferative assays for both hybrid AE37 (LRMK+HER2/neu:776-790) and AE36 (unmodified HER2/neu:776-790) peptides. Patients were clinically, radiographically, and pathologically monitored for recurrence of BCa.RESULTS: Thus far, 120 (49 PG, 71 AG) of the planned 200 patients have completed the primary series. The PG and AG have similar demographic/prognostic characteristics (Table 1). Toxicity profiles in the PG and AG were almost identical with no grade 4-5 local toxicities and no grade 3-5 systemic toxicities in either arm. Median DTH reaction to AE36 and AE37 increased significantly from baseline at 1 month after completion of the primary series in the PG group (AE36: 0.0±0.8 cm to 15.3 ±2.1 cm; AE37: 0.0±0.7 cm to 24.5±2.6 cm; p&amp;lt;0.0001) and did not change in the AG group (AE36: 0.0±0.5 cm to 0.0±1.4 cm; AE37: 0.0±0.7 cm to 0.0±1.6 cm; p&amp;gt;0.05). Median proliferation response to AE36 and AE37 increased significantly from baseline at 3, 6, and 12 months after the start of the vaccine series in the PG (p&amp;lt;0.015) and did not change significantly in the AG. At a median follow up of 13 months, there have been no (0.0%) recurrences in the PG (0/49) compared to 7.0% (5/71) in the AG (p=0.08).CONCLUSIONS: The modified peptide AE37 is safe with mild toxicities observed primarily due to the GM-CSF immunoadjuvant. AE37 elicits a strong HER2/neu-specific in-vivo and ex-vivo immune response to the modified and unmodified peptides. Importantly, the AE37 peptide vaccine may protect against BCa recurrences. peptideadjuvantp valueN=4971 Age (median)49520.06Node Positive75.5%62.1%0,16Grade 348.9%57.8%0.44Tumor ≥2 cm55.1%56.1%1ER/PR negative38.8%40.9%0.84HER2 over-expressor59.2%60.6%1 Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 3183. NOTE: This abstract was accepted for presentation at the Symposium after the Abstract Book went to press.