Abstract CT021: Tumor-associated immune cell PD-L1 expression and peripheral immune profiling: Analyses from CheckMate 141
Authors: Ferris Robert L. , Blumenschein George , Harrington Kevin , Fayette Jérôme , Guigay Joël , Colevas A. Dimitrios , Licitra Lisa , Kasper Stefan , Even Caroline , Worden Francis , Saba Nabil F. , Vokes Everett , Ho Cheryl , Concha-Benavente Fernando , Greenawalt Danielle , Jin Chelsea , Lynch Mark , Tahara Makoto , Haddad Robert , Monga Manish , Kao Henry , Gillison Maura 
Published: July 2017

Abstract
Introduction: In the phase 3 study CheckMate 141 (NCT02105636), patients with platinum-refractory head and neck squamous cell carcinoma treated with nivolumab (NIVO) had longer median overall survival (OS) (7.5 vs 5.1 months; P=0.01) and a higher objective response rate (all: 13.3 vs 5.8%; tumor PD-L1 ≥1%: 17 vs 1.6%) compared with investigator’s choice (IC) (Ferris et al. NEJM. 2016). This exploratory analysis evaluated the immune profile of patients from CheckMate 141, in context of tumor PD-L1 expression, and assessed the relationship with treatment (txt) outcomes.
Methods: PD-L1 expression in tumor and tumor-associated immune cells (TAIC) was analyzed at baseline (n=252) and assessed for association with clinical outcome. Tumor PD-L1 expression was quantitatively assessed using Dako IHC 28-8 pharmDx assay. TAIC PD-L1 abundance (numerous/intermediate, rare) and location (intra/intra-peritumoral, peritumoral) were qualitatively assessed (unvalidated). Peripheral blood (n=36) at baseline and day 43 was assessed for immune cell biomarkers by flow cytometry and analyzed by 2-way ANOVA with Sidak’s multiple comparisons test correction.
Results: Abundant PD-L1+ TAICs (numerous/intermediate) were associated with greater median OS with NIVO vs IC in tumors with PD-L1 ≥1% (abundant: 8.7 vs 4.4 months, hazard ratio [HR] and 95% CI 0.44 [0.27, 0.71] and rare: 6.7 vs 4.9 months, HR 0.88 [0.42, 1.86]) and PD-L1 &lt;1% (abundant: 12.7 vs 8.4 months, HR 0.73 [0.38, 1.41] and rare: 3.7 vs 4.6 months, HR 1.02 [0.45, 2.30]). Abundant, but not rare, PD-L1+ TAICs were associated with response to NIVO vs IC in tumors with PD-L1 ≥1% (abundant: 23 vs 0%, odds ratio [OR] and 95% CI 18.98 [1.03, 348.17] and rare: 17 vs 8%, OR 1.73 [0.21, 14.63]) and PD-L1 &lt;1% (abundant: 22 vs 14%, OR 1.61 [0.40, 6.49] and rare: 6 vs 14%, OR 0.39 [0.03, 5.10]). Intra/intra-peritumoral location of PD-L1+ TAICs was associated with greater median OS with NIVO vs IC in tumors with PD-L1 ≥1% (8.2 vs 4.4 months, HR 0.54 [0.33, 0.89]) and PD-L1 &lt;1% (7.1 vs 5.1 months HR 0.63 [0.34, 1.14]). Peritumoral location of PD-L1+ TAICs was associated with greater median OS with NIVO vs IC in tumors with PD-L1 ≥1% (8.7 vs 4.3 months HR 0.55 [0.27, 1.15]) but not PD-L1 &lt;1% (4.3 vs 10.6 months HR 1.72 [0.58, 5.08]). In the circulation, NIVO responders had higher total CD8+ T cells at baseline and on txt (both mean 22.5 vs 12.8%, P=0.04) and lower PD-1+ Tregs at baseline (mean 18.7 vs 33.4%, P&lt;0.01) and on txt (mean 11.7 vs 19.7%, P&lt;0.01) vs non-responders, and lower CTLA-4+ CD8+ T cells on txt vs at baseline (mean 8.2 vs 5.4%, P=0.02).
Conclusion: In this exploratory, qualitative immune profile analysis, abundance of PD-L1+ TAICs was associated with higher median OS and greater likelihood of response to NIVO vs IC. Response to NIVO may be associated with higher circulating CD8+ T cells and lower Tregs at baseline, and abundant PD-L1+ TAICs in the tumor microenvironment.
Citation Format: Robert L. Ferris, George Blumenschein, Kevin Harrington, Jérôme Fayette, Joël Guigay, A. Dimitrios Colevas, Lisa Licitra, Stefan Kasper, Caroline Even, Francis Worden, Nabil F. Saba, Everett Vokes, Cheryl Ho, Fernando Concha-Benavente, Danielle Greenawalt, Chelsea Jin, Mark Lynch, Makoto Tahara, Robert Haddad, Manish Monga, Henry Kao, Maura Gillison. Tumor-associated immune cell PD-L1 expression and peripheral immune profiling: Analyses from CheckMate 141 [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr CT021. doi:10.1158/1538-7445.AM2017-CT021