Abstract P4-13-02: Preliminary results for the phase 1 trial of a dual HER2 peptide cancer vaccine in breast and ovarian cancer patients
Authors: Berry JS , Trappey AF , Vreeland TJ , Schneble EJ , Clifton GT , Hale DF , Sears AK , Ponniah S , Shumway NM , Mittendorf EA , Peoples GE 
Published: August 2014

Abstract
BACKGROUND: HER2 is a commonly expressed tumor-associated antigen in breast (BrCa) and ovarian cancer (OvCa) and, therefore, an attractive target for immunotherapy. We have investigated HER2-derived peptides as vaccines mixed with GM-CSF to include GP2 (a HLA-A2 and HLA-A3 restricted, CD8+ eliciting epitope) and AE37 (a HLA unrestricted, MHC class II, CD4+ eliciting epitope). Both peptide vaccines (PV) have shown clinical promise individually. There is clear rationale for combining GP2 and AE37 to elicit a more robust immune response (IR) of both CD4+ and CD8+ T cells. Here, we summarize initial toxicity (tox) and in vivo IR data from a phase 1 trial of the combined PV.
METHODS: The trial is being performed as a five cohort, 3+3 dose-escalation, safety trial. Clinically disease-free, HLA-A2+ and A3+, BrCa and OvCa patients with tumors expressing any level of HER2 (IHC 1-3+) and who have completed standard-of-care therapy are accrued. In the first cohort, three patients received six, monthly intradermal inoculations (R1-R6) of 100mcg of AE37, 100mcg of GP2, and 125mcg of GM-CSF or 100:100:125. The second cohort received 250mcg of AE37, 100mcg of GP2, and 125mcg of GM-CSF or 250:100:125. Three additional cohorts were vaccinated: 250:250:125, 500:250:125, and 500:500:125. Toxicity was graded 48-72 hours post vaccination using NCI Toxicity Criteria v4.0. After each inoculation, local reactions (LR) are measured via the sensitive ballpoint pen method and reported as the orthogonal mean (OM). IR is assessed in vivo by delayed type hypersensitivity (DTH) reactions with separate intradermal inoculations of AE37, AE36, and GP2 antigens, measured both pre-vaccination (R0) and after the vaccine series (R6) via the sensitive ballpoint pen method, and reported as the OM. Means were compared using paired t-tests.
RESULTS: 28 patients enrolled; 8 withdrew consent, 1 recurred prior to completing R6, 3 had an intercurrent illness, 14 patients completed R1-R6, and the vaccine series is ongoing in 2 patients. Six patients did not receive any inoculations and, therefore, are not included in this safety analysis. In 22 patients, the vaccine was well tolerated (max local tox: 23% Grade (Gr) 1, 73% Gr 2, 4% Gr 3; max systemic tox: 14% Gr 0, 50% Gr 1, 36% Gr 2). No dose-limiting toxicity was observed. For the 14 patients who completed the VS, the median age was 51(35-83). Breast tumor size was 3.3±1.1cm and ovarian tumor size was 10.0±2.3cm. Compared to GP2 LR at R1 (15.5±4.1mm), LR increased at R2 (31.7±5.9mm), R3 (42.9±7.4mm), R4 (35.3±7.3mm), R5 (45.0±9.9mm), and R6 (25.9±6.7mm, p = 0.17). Compared to the AE37 LR at R1 (18.5±3.8mm), LR increased at R2 (37.3±6.7mm), R3 (36.4±4.6mm), R4 (42.2±5.9mm), R5 (46.0±8.9mm), and R6 (36.2±6.6mm). Unless stated, all LR p-values &lt; 0.05. After the VS, AE37 DTH increased from 0.0±0.0mm to 19.6±6.7mm (p&lt;0.01), AE36 DTH increased from 0.0±0.0mm to 10.3±3.9mm (p&lt;0.01), and GP2 DTH reactions increased from 0.3±0.2mm to 4.1±2.0mm (p = 0.056).
CONCLUSIONS: Initial results from a phase I trial of a vaccine combining GP2 and AE37 peptides show that dual administration of the peptides is well tolerated at all tested dosing levels. Additionally, the combination is capable of stimulating strong peptide-specific in vivo immune responses. Continued testing of this vaccination strategy is underway.
Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P4-13-02.