In a phase Ib clinical trial, cabozantinib (anti-VEGFR2, c-MET, AXL) and nivolumab (anti-PD-1) were used as a neoadjuvant therapy in patients with HCC that was not eligible for resection. Neoadjuvant therapy enhanced tumor resectability. 12 patients were able to undergo surgical resection; 1 achieved a complete pathological response and 4 achieved major pathological responses. Responders showed signs of increased antitumor immunity, including increased tertiary lymphoid structures and T cells, and decreased HCC cells. Aggregates of B cells were associated with responses, while Arg-1+ macrophages were associated with resistance.
Contributed by Lauren Hitchings
ABSTRACT: A potentially curative hepatic resection is the optimal treatment for hepatocellular carcinoma (HCC) but most patients are not candidates for resection and most resected HCCs eventually recur. Until recently, neoadjuvant systemic therapy for HCC has been limited by a lack of effective systemic agents. Here, in a single-arm phase 1b study, we evaluated the feasibility of neoadjuvant cabozantinib and nivolumab in patients with HCC, including patients outside of traditional resection criteria (ClinicalTrials.gov ID NCT03299946). Of 15 patients enrolled, 12 (80%) underwent successful margin-negative resection and 5 out of 12 (42%) had major pathological responses. In-depth biospecimen profiling demonstrated an enrichment in effector T cells, as well as tertiary lymphoid structures, CD138+ plasma cells, and a distinct spatial arrangement of B cells in responders compared to nonresponders, indicating an orchestrated B cell contribution to antitumor immunity in HCC.
Author Info: (1) Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA. (2)
Department of Pathology, Johns Hopkins U
Author Info: (1) Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA. (2)
Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA. (3) Fluidigm Corporation, San Francisco, CA, USA. 4Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD, USA. (5) Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA. (6) McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA. (7) Division of Biostatistics and Bioinformatics, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA. (8) Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, USA. (9) Department of Applied Mathematics and Statistics, Johns Hopkins University Whiting School of Engineering, Baltimore, MD, USA. (10) These authors contributed equally: Won Jin Ho, Qingfeng Zhu.
