Feasibility study of multiple HLA-class IA restricted peptide vaccines (KRM-19) for metastatic triple negative breast cancer (TNBC).

Abstract

164 Background: Our previous phase II clinical trial has indicated that the therapeutic selected personalized peptide vaccines (PPV) were effective for boosting anticancer immunity and the immune response after PPV was associated with the clinical outcome as a prognostic factor for metastatic breast cancer (mBC). Based on the data from the PPV studies, we have conducted an early phase II study to evaluate the safety and the efficacy of a new regimen using multiple peptide vaccines (KRM-19) for pts with metastatic TNBC. Methods: KRM-19 consisted of 19 mixed peptides which were chosen from the previously reported 31 PPVs according to their anti-tumor immunologic effect and safety profile for mBC pts. All patients had histologically confirmed measurable ER-PgR-Her2- mBC and their human leukocyte antigen (HLA)-A molecules should be each of -A2, A3, A11, A24, A26, A31, or A33. KRM-19 (19mg/ml) was administrated subcutaneously in order with schedule of every week for a total of 6 doses. The concurrent conventional chemo- and/or endocrine therapy was not permitted for the combination, but was available for post-study treatment. Measurement of peptide-specific cytotoxic T lymphocyte (CTL) and IgG responses were conducted before and after vaccination. Levels of IgG reactive to each of the 19 peptides in the pre- and post-vaccination plasma were measured using the LUMINEX system at every 6 vaccinations. Peptide-specific CTL responses were examined by INF-ɤ ELISPOT. Clinical response was evaluated by RECIST criteria. Results: 10 patients with refractory metastatic TNBC received all 6 vaccines and 10/10 patients experienced Grade 1-2 skin reaction at injection site, 5/10 pts had Grade 2-3 liver function disorder, 3/10 and 1/10 pts had Grade 2 bone marrow suppression and nausea, respectively. The clinical responses were assessed in 8 pts included 1 PR case, 4 SD cases, and 3 PD cases. The evaluation of other clinical and immunologic data is underway. Conclusions: Subcutaneous KRM-19 vaccine administration was safe and resulted in a 12.5% objective response and 62.5% clinical benefit rate in TNBC pts, warranting further larger scale study. Clinical trial information: UMIN000014616.