Correlative analyses of the SARC028 trial reveal an association between sarcoma-associated immune infiltrate and response to pembrolizumab

Emily Z. Keung, Melissa Burgess, Ruth Salazar, Edwin R. Parra, Jaime Rodrigues-Canales, Vanessa Bolejack, Brian A. Van Tine, Scott M. Schuetze, Steven Attia, Richard F. Riedel, James Hu, Scott H. Okuno, Dennis A. Priebat, Sujana Movva, Lara E. Davis, Damon R. Reed, Alexandre Reuben, Christina L. Roland, Denise Reinke, Alexander J. LazarWei Lien Wang, Jennifer A. Wargo, Hussein A. Tawbi

Research output: Contribution to journalArticle

5 Scopus citations

Abstract

Purpose: We recently reported a 17.5% objective RECIST 1.1 response rate in a phase II study of pembrolizumab in patients with advanced sarcoma (SARC028). The majority of responses occurred in undifferentiated pleomorphic sarcoma (UPS) and dedifferentiated liposarcoma (DDLPS). We sought to determine whether we can identify immune features that correlate with clinical outcomes from tumor tissues obtained pre- and on-treatment. Patients and Methods: Pretreatment (n ¼ 78) and 8-week on-treatment (n ¼ 68) tumor biopsies were stained for PD-L1 and multiplex immunofluorescence panels. The density of positive cells was quantified to determine associations with anti-PD-1 response. Results: Patients that responded to pembrolizumab were more likely to have higher densities of activated T cells (CD8þ CD3þ PD-1þ) and increased percentage of tumor-associated macrophages (TAM) expressing PD-L1 pre-treatment compared with non-responders. Pre-treatment tumors from responders also exhibited higher densities of effector memory cytotoxic T cells and regulatory T cells compared with non-responders. In addition, higher density of cytotoxic tumor-infiltrating T cells at baseline correlated with a better progression-free survival (PFS). Conclusions: We show that quantitative assessments of CD8þ CD3þ PD-1þ T cells, percentage of TAMs expressing PD-L1, and other T-cell densities correlate with sarcoma response to pembrolizumab and improved PFS. Our findings support that multiple cell types present at the start of treatment may enhance tumor regression following anti-PD-1 therapy in specific advanced sarcomas. Efforts to confirm the activity of pembrolizumab in an expansion cohort of patients with UPS/DDLPS are underway.

Original languageEnglish (US)
Pages (from-to)1258-1266
Number of pages9
JournalClinical Cancer Research
Volume26
Issue number6
DOIs
StatePublished - Mar 15 2020

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Keung, E. Z., Burgess, M., Salazar, R., Parra, E. R., Rodrigues-Canales, J., Bolejack, V., Van Tine, B. A., Schuetze, S. M., Attia, S., Riedel, R. F., Hu, J., Okuno, S. H., Priebat, D. A., Movva, S., Davis, L. E., Reed, D. R., Reuben, A., Roland, C. L., Reinke, D., ... Tawbi, H. A. (2020). Correlative analyses of the SARC028 trial reveal an association between sarcoma-associated immune infiltrate and response to pembrolizumab. Clinical Cancer Research, 26(6), 1258-1266. https://doi.org/10.1158/1078-0432.CCR-19-1824