Abstract CT202: A Phase I study of a first-in-man carbohydrate mimetic-peptide vaccine in Stage IV breast cancer subjects

Purpose: High levels of Tumor Associated Carbohydrate Antigens (TACAs) correlate with metastasis and worse prognosis. In this dose-escalation Phase I clinical trial, we analyzed the safety and immune response to a reverse-engineered Carbohydrate Mimetic Peptide (CMP), named P10s, in 6 subjects with advanced breast cancer. Experimental Design: A Phase I dose-escalation trial was conducted to determine a maximum tolerated dose of vaccine plus adjuvant in two cohorts of stage IV breast cancer patients. This trial utilized the traditional 3+3 cohort design, with 3 subjects at each dose if no toxicities were observed. Research participants were restricted to females of all races with histologically or cytologically confirmed stage IV breast cancer (newly diagnosed or relapsed after primary or adjunctive therapy and which have not required a treatment change for 2 months). P10s-PADRE was formulated at 300 and 500 ug/injection with MONTANIDE™ ISA 51 VG for the 1st and 2nd cohorts, respectively. Doses of the appropriate formulation were administered to research participants subcutaneously in rotating injection sites in the abdomen on weeks 1, 2, 3, 7 and 9. The primary endpoint was the safety of CMP vaccination. The secondary endpoints were immune responses as measured by antibody titer to P10s and reactivity to TACA-expressing human breast-cancer cell lines. Results: 16 women were consented, with 6 subjects receiving the CMP vaccine. Three subjects completed the vaccination schedule at 300 μg P10s-PADRE per injection, and 3 completed immunizations at the 500-μg dose. Patients were evaluated for signs of toxicity during and after vaccination. Adverse events were graded according to the National Cancer Institute's Common Terminology Criteria for Adverse Events Version 4.0. Toxicities assessed were the laboratory parameters listed in the study calendar, as well as any sign or symptom found during the history and physical examination not noted at pre-study or on the baseline evaluation. No dose-limiting toxicities were observed in the subjects. P10s vaccination was well-tolerated. All 6 subjects displayed a persistent IgG response to P10s after vaccination, and induced serum and plasma antibodies displayed cross-reactivity to TACA-expressing human breast-cancer cell lines. Antibody induced by P10s in 5 of the 6 subjects displayed statistically significant cytotoxic functionality to several human breast-cancer cell lines including a Trastuzumab-resistant line. Conclus