Abstract CT017: A Phase Ib of a combination of two chimeric (Trastuzumab-like and Pertuzumab-like) HER-2 B cell peptide vaccine emulsified in ISA 720 and nor-MDP adjuvant in patients with advanced solid tumors

Abstract

Abstract Background: HER-2 is a transmembrane receptor that is overexpressed in multiple epithelial tumors. We have previously shown that a first generation HER-2 B-cell peptide vaccine targeting epitopes (628-647) and (316-339) was safe and relatively active. We recently developed a novel B-cell epitope specific vaccine (HER-Vaxx) consisting of epitopes derived from the extracellular domain of HER-2 that correspond to amino acid sequences 597-626 (pertuzumab binding site) and 266-296 (trastuzumab binding site). Methods: This first-in-human Phase 1b study evaluated the safety, optimal immunologic/biologic dose (OID/OBD) and immunogenicity of HER-Vaxx. Using a 3+3 dose escalation design, 3 patients (pts) were treated at each dose level (DL). If <2 pts experience dose-limiting toxicity (DLT), we required an additional 3 pts to be entered at that DL for OID/OBD assessment (defined as the dose level inducing a strong immunogenic response for 5 out of 6 patients). We also required that at least 6 patients at each DL to receive 3 inoculations of the combination vaccines at 3-week intervals and that < 2 of the 6 pts experience DLT before dose escalation. DLs were 1.0 mg (DL1), 1.5 mg (DL2), 2.0 mg (DL3) and 2.5 mg (DL4) of each peptide. Each dose contained 0.025 mg of n-MDP. Results: 49 patients with metastatic and/or recurrent solid tumors and a median of 4 prior lines of chemotherapy received at least one inoculation of HER-vaxx. Common related toxicities include injection site reactions (56% grade 1/2 and 5% grade 3/4). There were no DLTs. The OID/OBD was found to be DL 2 (1.5 mg of each peptide vaccine).A total of 28 patients received ≥ 3 vaccinations including 2 with a partial response and 14 with stable disease. Of those, 6 patients received at least one 6-month boost. The vaccine generated sustained humoral response eliciting HER-2 specific antibodies in the majority of responding patients. Conclusion: We demonstrate that HER-Vaxx is well tolerated and able to generate sustained anti-HER-2 immune response. Given the promise, continuous development of the vaccine is ongoing at the suggested OBD in HER-2 overexpressing tumors. Citation Format: Tanios Bekaii-Saab, Lai Wei, Robert Wesolowski, Daniel Ahn, Christina Wu, Maryam Lustberg, Amir Mortazavi, Bhuvaneswari Ramaswamy, Jay Overholser, Pravin Kaumaya. A Phase Ib of a combination of two chimeric (Trastuzumab-like and Pertuzumab-like) HER-2 B cell peptide vaccine emulsified in ISA 720 and nor-MDP adjuvant in patients with advanced solid tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr CT017.