Abstract 3114: Correlation between response to atezolizumab and PD-L1 tumor expression in pediatric and young adult patients enrolled in the phase I/II iMATRIX-atezo study

Abstract

Abstract Introduction The iMATRIX-atezo trial (NCT02541604) assessed the safety and pharmacokinetics (primary objectives) and preliminary activity (secondary objective) of atezolizumab in pediatric and young adult patients with refractory/relapsed solid tumors, including Hodgkin’s lymphoma (HL) and non-Hodgkin’s lymphoma (NHL). Atezolizumab targets PD-L1 expressed by tumor cells leading to an enhanced anticancer T-cell response. The purpose of this analysis was to investigate the association between PD-L1 expression and response to atezolizumab in patients participating in the iMATRIX-atezo trial. Methods Patients aged <30 years received atezolizumab every 3 weeks until loss of clinical benefit. Biomarkers were analyzed across cohorts and by response to atezolizumab, with a minimum follow up of 6 months. Response was assessed by RECIST, modified International Neuroblastoma Response Criteria, Response Criteria for Malignant Lymphoma, and RANO. Pretreatment tissues were examined by immunohistochemistry for: T/B/NK cell markers, tumor-infiltrating lymphocytes (TILs) and PD-L1 expression in tumor cells [TC] and immune cells [IC]. Blood samples were analyzed for T/B/NK cell constitution by flow cytometry. Tumor mutational burden (TMB) was determined by FoundationOne® next-generation sequencing. Results Eighty-seven patients received ≥1 dose of atezolizumab. Of 11 patients with high PD-L1 expression (TC2/TC3/IC2/IC3) and response data, four had a partial response (PR; two with HL, one with NHL, one with a rhabdoid tumor), one had stable disease (SD) and six had progressive disease (PD). Of 52 patients with low or no PD-L1 expression (TC1/TC0/IC1/IC0) and response data, no responses were observed. Though numerically limited, PD-L1 expression and response were significantly correlated (p=0.0006, Fisher’s exact test). HL (8/9 patients) and NHL (2/3 patients) cohorts had the greatest proportion of patients with high baseline PD-L1. Levels of CD8+ (T cells), CD20+ (B cells) and stromal TILs at baseline were significantly associated with patients’ response status (p<0.05, Mann-Whitney U test). High PD-L1 expression correlated with elevated expression of other tissue-based immune biomarkers, except NK cells. Blood biomarkers did not correlate with tumor-based counterparts. No tumors were TMB high; all were <16 mutations/megabase. Conclusions High PD-L1 expression compared with low or no expression was associated with a greater response to atezolizumab, notably in patients with HL and NHL. Despite small sample sizes and limited responses, these biomarker data support adult studies citing the association between PD-L1 and response to atezolizumab; data suggest that PD-L1 may also be a predictor of atezolizumab response in pediatric and young adult patients. Citation Format: Katherine E. Hutchinson, Minlei Liao, Mufiza Farid-Kapadia, Francis Donaldson, Nga Wan Rachel Tam, Lingyan Helen Fu, Meghna Das Thakur, C. Michel Zwaan, Birgit Geoerger, Lynley V. Marshall, Tanya Trippett, Gianluca Rossato. Correlation between response to atezolizumab and PD-L1 tumor expression in pediatric and young adult patients enrolled in the phase I/II iMATRIX-atezo study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 3114.