Phase I Immunotherapy Trial with Two Chimeric HER-2 B-Cell Peptide Vaccines Emulsified in Montanide ISA 720VG and Nor-MDP Adjuvant in Patients with Advanced Solid Tumors.

摘要: Purpose: This first-in-human phase I study (NCT 01417546) evaluated the safety profile, optimal immunologic/biological dose (OID/OBD), and immunogenicity of combination two peptide B-cell epitope vaccines engineered to represent trastuzumab- pertuzumab-binding sites. Although trastuzumab pertuzumab have been approved for clinical use, patients often develop resistance these therapies. We advanced a new paradigm in immunotherapy that focuses on humoral responses based conformational vaccines. Patients Methods: The vaccine is comprised chimeric HER-2 incorporating “promiscuous T-cell epitope.” were immunized with constructs emulsified nor-muramyl-dipeptide adjuvant water-in-oil Montanide ISA 720VG vehicle. Eligible metastatic and/or recurrent solid tumors received three inoculations every 3 weeks. Results: Forty-nine median 4 prior lines chemotherapy at least 1 vaccination. Twenty-eight completed vaccination regimens. Six six-month boost after regimen, one patient 7 boosts. No serious adverse reactions or dose-limiting toxicities observed. was well tolerated level 2 as recommended II dose. most common related toxicity all injection-site (24%). Two had partial response, 14 stable disease, 19 progressive disease. Conclusions: safe, exhibits antitumor activity, shows preliminary indication may avoid therapeutic offer promising alternative monoclonal antibody