OT1-02-10: Phase I-II Study of HER2 Vaccination with Poly(I) • Poly(C12U) (Ampligen®) as an Adjuvant in Optimally Treated Breast Cancer Patients.
Authors: Higgins DM , Childs J , Parker S , Guthrie KA , Disis ML , Salazar LG 
Published: June 2012

Abstract
Background
Despite improved response rates and overall survival, many HER2+ breast cancer (BC) patients have disease relapse suggesting residual microscopic disease. HER2 vaccines given with adjuvants that can enhance, sustain, and skew antigen immunogenicity toward a Th1 phenotype could induce robust tumor-specific Th1 immunity resulting in immunologic eradication of residual tumor cells and potentially prevent relapse. One such adjuvant is Ampligen which is highly selective as a TLR-3 agonist. Our pre-clinical studies show a dose effect in the tumor prevention efficacy of Ampligen when given as an adjuvant with vaccines. We hypothesize HER2 peptide vaccination given with standard adjuvant 100mcg GMCSF and Ampligen can induce a higher incidence and magnitude of protective HER2−specific Th1 immunity than with GMCSF alone.
Trial design: Phase I-II randomized 2-stage HER2 vaccine study. Stage I will enroll 40 patients (10/arm) into one of 4 Ampligen dose arms (4, 20, 79, or 495 mcg + HER2 vaccine). The Ampligen “maximum biologic dose” (MBD), the dose with the highest incidence/magnitude of immune response and lowest incidence of toxicity will be defined. Stage II will enroll 48 patients (24/arm) receiving Ampligen MBD + HER2 vaccine + GMCSF or HER2 vaccine + GMCSF to evaluate if Ampligen MBD increases the incidence and magnitude of immunity vs HER2 vaccine + GMCSF alone. Patients will be enrolled sequentially and randomized equally into all arms via a permuted block design. Patients will receive 3 monthly vaccines. Toxicity and immune response will be assessed.
Aims: 1) To evaluate toxicity and define the MBD of Ampligen as an adjuvant with HER2 vaccination 2) determine if Ampligen MBD when combined with GMCSF as adjuvant and HER2 vaccination increases incidence/magnitude of HER2 Th1 immunity compared to standard GMCSF alone.
Eligibility criteria: Stage II–IV HER2+ BC patients who: 1) have completed definitive standard treatment, and in clinical remission 2) 14 days post chemotherapy and steroids 3) have adequate blood counts 4) are off trastuzumab 5) have no active autoimmune disease.
Statistical methods: In aim 1, we expect mild toxicity between the 4 dose arms, thus lack of efficacy based on incidence of immune response will be evaluated. Six responses must be observed within a dose arm to move forward based on historical 60% response rate (RR) with standard GMCSF (probability of continuing if true RR is 40% and 70% is 0.17, 0.85, respectively). In aim 2, 24 patients/arm provides 80% power to detect 40% difference in incidence of immune response between the 2 groups (Pearson chi-square test, two-sided alpha of 0.05) and 82% power to assess a 0.85 SD unit difference in change between control and MBD, based on a 2-sample t-test (p=0.05) and effect size defined as the difference in the means divided by the common SD. Incidences of HER2 Th1 immunity will be compared across treatment arms via Pearson chi-square test; magnitude of immune response will be compared across groups via linear regression model.
Study Accrual: Target accrual is 88 patients: Stage 1 (n=40) and Stage II (n=48). There has been no accrual at this time.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr OT1-02-10.