Abstract P3-10-16: Phase I/II of Personalized Neoantigen Peptide-Based Vaccine (PNeoVCA) in Combination with Pembrolizumab in Patients with Early-Stage Triple-Negative Breast Cancer with Residual Disease after Neoadjuvant Chemotherapy

Abstract Background: While immune checkpoint inhibitor (ICI) has significantly improved outcomes in patients with early-stage triple-negative breast cancer (TNBC), patients with residual disease after pembrolizumab-based neoadjuvant chemotherapy continue to have particularly poor outcomes. Patients with larger amounts of residual disease with residual cancer burden (RCB)-III and RCB-II had extremely poor outcomes, with 72.5% and 25.5% of patients developing recurrence within the first 3 years, respectively. Recent breakthroughs in identifying personal neoantigens via a comprehensive analysis of cancer sequencing data have brought increased attention to neoantigen cancer vaccines. Personalized cancer vaccines targeting neoantigens have shown early promising results in melanoma. While neoantigens have recently been investigated in some cancer types, the current neoantigen prediction algorithms have often focused on the MHC class-I subtype, single nucleotide mutations (SNM), small insertions, and deletions (INDEL). We recently developed an informatics workflow, REAL-neo, for the identification, quality control (QC), and prioritization of both class-I and class-II human leukocyte antigen (HLA) bound neoantigens that arise from somatic SNM, INDEL, aberrant RNA splicing, and gene fusions, generating much more potent neoantigen candidates. Furthermore, we demonstrated robust T-cell response and prolonged survival by combining ICI and cancer vaccines in preclinical models. This phase I/II clinical trial is in progress to assess the safety, feasibility, and immunogenicity of personalized neoantigen vaccines in combination with pembrolizumab in patients with advanced solid cancers with a phase II extension cohort in patients with early-stage TNBC with residual disease after neoadjuvant chemotherapy. Methods: Key eligibility criteria include females ≥ 18 years old with histologically confirmed stage I-III TNBC (ER<10%, PR <10%, and HER2 negative per ASCO/CAP guideline. Patients with evidence of residual disease ≥ 1 cm after neoadjuvant pembrolizumab-based chemotherapy on imaging will be enrolled in the pre-screening phase prior to surgery to collect fresh frozen samples for sequencing. After surgery, patients with histologically confirmed RCB-II and RCB-III will be pre-registered, and patient samples will be sequenced to identify patient-specific neoantigens using the REAL-neo algorithm. Patients will continue with standard-of-care therapy based on the treating physician's choice. Once PNeoVCA vaccine production is completed, eligible patients will receive the vaccine consisting of up to 20 peptides delivered with GM-CSF as an adjuvant. PNeoVCA will be administered with 4-5 peptides at 300 mcg/peptide and GM-CSF 125 mcg per injection site in each limb in combination with Pembrolizumab 200 mg i.v. PNeoVCA will be given via subcutaneous injection on days 1, 4, 8, 15, and 21, with boosters in weeks 5 and 8. Clinical trial information: NCT05269381 Citation Format: Saranya Chumsri, Yanyan Lou, Qian Shi, Jordan Reynolds, Brian Necela, Nadine Norton, Rohit Rao, Pooja Advani, Kostandinos Sideras, Michael Gustafson, Yan Asmann, Keith Knutson. Phase I/II of Personalized Neoantigen Peptide-Based Vaccine (PNeoVCA) in Combination with Pembrolizumab in Patients with Early-Stage Triple-Negative Breast Cancer with Residual Disease after Neoadjuvant Chemotherapy [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2024; 2024 Dec 10-13; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2025;31(12 Suppl):Abstract nr P3-10-16.