@article{0b4f8723102b4239a04a4d0a6346cf14,
title = "Correlative analyses of the SARC028 trial reveal an association between sarcoma-associated immune infiltrate and response to pembrolizumab",
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 (CD8{\th} CD3{\th} PD-1{\th}) 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 CD8{\th} CD3{\th} PD-1{\th} 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.",
author = "Keung, {Emily Z.} and Melissa Burgess and Ruth Salazar and Parra, {Edwin R.} and Jaime Rodrigues-Canales and Vanessa Bolejack and {Van Tine}, {Brian A.} and Schuetze, {Scott M.} and Steven Attia and Riedel, {Richard F.} and James Hu and Okuno, {Scott H.} and Priebat, {Dennis A.} and Sujana Movva and Davis, {Lara E.} and Reed, {Damon R.} and Alexandre Reuben and Roland, {Christina L.} and Denise Reinke and Lazar, {Alexander J.} and Wang, {Wei Lien} and Wargo, {Jennifer A.} and Tawbi, {Hussein A.}",
note = "Funding Information: This study was funded by the Sarcoma Alliance for Research through Collaboration, Pittsburgh Cure Sarcoma, Merck, and The University of Texas MD Anderson Cancer Center (H. Tawbi). E.Z. Keung was supported by National Institutes of Health (NIH) grant T32 CA009599. We thank the patients and their families, the investigators, and participating study teams. Funding Information: B.A. Van Tine is an employee/paid consultant for Epizyme, Lilly, CytRX, Janssen, Immune Design, Daiichi Sankyo, Adaptimmune, Plexxicon, and Bayer, reports receiving commercial research grants from Merck, Pfizer, and Tracon, other commercial research support from Lilly, GlaxoSmithKline, and Adaptimmune, and speakers bureau honoraria from Lilly, Caris, Adaptimmune, and Janssen. S. Attia is an employee/paid consultant for Desmoid Tumor Research Foundation, AB Science, TRACON Pharma, Bayer, Novartis, Daiichi Sankyo, Lilly, Immune Design, Karyopharm Therapeutics, Epizyme, Blueprint Medicines, Genmab, CBA Pharma, Merck, Philogen, Gradalis, Deciphera, Takeda, Incyte, Springworks, Adaptimmune, Advenchen Laboratories, Bavarian Nordic, PTC Therapeutics, BTG, GlaxoSmith-Kline, and FORMA Therapeutics. R.F. Riedel is an employee/paid consultant for Bayer, Blueprint, EISAI, EMD Serono, Janssen, Lilly, Loxo, and Ignyta, and holds ownership interest (including patents) in Limbguard, LLC. S. Movva is an employee/ paid consultant for Genmab, and reports receiving commercial research grants from Novartis and Takeda. D.R. Reed is an employee/paid consultant for Epizyme, Janssen, LOXO, and Shire. C.L. Roland reports receiving commercial research grants and other remuneration from Bristol-Myers Squibb. A.J. Lazar is an employee/paid consultant for Bristol-Myers Squibb, and reports receiving commercial research grants from Publisher Copyright: {\textcopyright} 2020 American Association for Cancer Research.",
year = "2020",
month = mar,
day = "15",
doi = "10.1158/1078-0432.CCR-19-1824",
language = "English (US)",
volume = "26",
pages = "1258--1266",
journal = "Clinical Cancer Research",
issn = "1078-0432",
publisher = "American Association for Cancer Research Inc.",
number = "6",
}