Ziv-aflibercept plus pembrolizumab in patients with advanced melanoma resistant to anti-PD-1 treatment

• DOI: 10.1007/s00262-023-03593-2
• Publication Date: 2024-01-18T12:01:32Z
• Authors: Joanna Baginska; Allison Nau; Ilana Gomez Diaz; Anita Giobbie-Hurder; Jason Weirather; Juliana Vergara; Charlotte Abrecht; Margaret Hallisey; Jenna Dennis; Mariano Severgnini; Julia Huezo; Isabella Marciello; Osama Rahma; Michael Manos; Andrew S. Brohl; Philippe L. Bedard; Daniel J. Renouf; Elad Sharon; Howard Streicher; Patrick A. Ott; Elizabeth I. Buch...; F. Stephen Hodi
• Keywords: Aflibercept; Combination therapy

Abstract Background Vascular endothelial growth factor is associated with reduced immune response and impaired anti-tumor activity. Combining antiangiogenic agents checkpoint inhibition can overcome this suppression enhance treatment efficacy. Methods This study investigated the combination of ziv-aflibercept anti-angiogenic therapy pembrolizumab in patients advanced melanoma resistant to anti-PD-1 treatment. Baseline on-treatment plasma PBMC samples were analyzed by multiplex protein assay mass cytometry, respectively. Results In Phase 1B (NCT02298959), ten PD-1-resistant treated a (at 2–4 mg/kg) plus 2 mg/kg), administered intravenously every weeks. Two (20%) achieved partial response, two experienced stable disease (SD) as best response. The responders had mucosal melanoma, while both SD ocular melanoma. demonstrated clinical activity acceptable safety, despite occurrence adverse events. Changes analytes such platelet-derived PD-L1 explored, indicating potential alterations myeloid cell function. Higher levels circulating CXCL10 non-responding may reflect pro-tumor Specific subsets γδ T cells poor outcomes, suggesting T-cell function patients. Conclusions Although limited sample size follow-up, these findings highlight need for further research improve outcomes anti-PD-1-resistant Trial registration number NCT02298959.