Advances in the immunology have identified that interleukin (IL)-17 and IL-35 are cytokines with diverse functions, serving important roles in autoimmune diseases and chronic inflammation. Checkpoint inhibitor pneumonitis (CIP) is focal or diffuse lung inflammation induced by immune checkpoint inhibitors and the underlying pathogenesis has not been fully explored. The aim of the present study was to investigate the roles of IL-17A and IL-35, and the correlation between their levels and different T cell subsets in CIP. The levels of IL-17A and IL-35 in peripheral blood and bronchoalveolar lavage fluid (BALF) were measured in patients with non-small cell lung cancer (NSCLC) with CIP, and the corresponding controls. The percentages of helper T lymphocyte (Th)1, Th2 and Th17 cells, and regulatory T cells (Tregs) in the peripheral blood were synchronically detected. Serum levels of IL-17A and IL-35 were significantly increased at the time of CIP diagnosis compared with the baseline, and significantly decreased upon clinical recovery or improvement. IL-17A and IL-35 were also increased in the BALF during the development of CIP compared with the baseline. Serum levels of IL-17A were positively correlated with the percentages of Th1 and Th17 cells as well as the ratio of Th17 to Tregs, but negatively associated with the frequency of Tregs in CIP. Serum levels of IL-35 were positively correlated with the percentages of Th1 and Tregs, and with the ratio of Th1 to Th2 cells in CIP. A higher frequency of Th1 and Th17 cells, as well as higher ratios of Th17 to Tregs and Th1 to Th2 cells were detected upon development of CIP comparing with the baseline. These data suggested that the activation of Th1 and Th17 cells, as well as Treg inhibition contributed to the imbalanced ratios of Th1 to Th2 and Th17 to Tregs, which resulted in increased secretion of IL-17A and IL-35 in the plasma and BALF; this may present a valuable index to monitor the development and severity of CIP in patients with NSCLC receiving immunotherapy.

9112 Background: Our preclinical study suggested combination of PD-1 monoclonal antibody SHR-1210 and VEGFR 2 inhibitor apatinib significantly improved antitumor effects. This was an open-label, multi-center, phase 1/2 study of intravenous SHR-1210 plus oral apatinib in patients with advanced NSCLC. Here, we reported preliminary efficacy and safety outcomes of SHR-1210 plus apatinib in patients with wild‐type EGFR and ALK. Methods: In dose-escalation phase, advanced non-squamous NSCLC patients (pts) previously treated with at least 2nd line chemotherapy were enrolled to explore 2 dose levels of apatinib (250, 375mg/d) + SHR-1210 (200mg, q2w). 250mg/d of apatinib was selected to be combined with SHR-1210 in phase II trial. Pts previously treated with 1st line platinum-based chemotherapy were enrolled. Primary endpoint was ORR per RECIST 1.1. Archived or fresh tumor tissues and blood samples were taken before the treatment, PD-L1 expression and tumor mutation burden (TMB) were tested and correlated with efficacy. TMB was detected by Oseq-pan cancer panel (including 636 genes and 1.95Mb), and then calculated by in-house algorithm developed by BGI Genomics Co., Ltd. Results: 96 pts with advanced non-squamous NSCLC harboring wild‐type EGFR and ALK were recruited . 23 had ≥2 prior lines of systemic treatment, and 73 had 1 prior line of treatment. Median age was 57, male 79.8%, adenocarcinoma 93.9%, ex-smokers 56.7%. ORR and DCR in 91evaluable pts were 29.7% and 81.3%, respectively. Blood TMB (bTMB) test was available in 80/91 evaluable patients and the cut-point was 1.54 muts/Mb as determined by receiver operating characteristic curve. ORR in pts with high bTMB was 50% (19/38). At data cutoff of 20 Jan 2019, 20/27 responders were still on treatment (table). Across all 96pts, 54(56.2%) grade ≥3 TRAEs. AEs of grade ≥3 occurring in 2 or more pts included hypertension, hand-foot syndrome, gamma-glutamyl transferase increase, proteinuria, abnormal hepatic function and alkaline phosphatase increase. Conclusions: SHR-1210 plus apatinib demonstrated promising anti-tumor activity with acceptable safety in patients with non-squamous NSCLC, especially in those with high bTMB. Prospective study is needed to validate the clinical outcome and bTMB as a predictor of efficacy. Clinical trial information: NCT03083041. [Table: see text]

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e21193 Background: In the past 3 years, immunotherapy has revolutionized the treatment paradigm of advanced non–small cell lung cancer (NSCLC). Checkpoint inhibitors showed promising results in the treatment of patients with advanced NSCLC with improved outcomes in clinical trials, but results from clinical trials can be difficult to generalize to real-world patient populations. Herein, we disclose the data of efficacy profile of toripalimab, a novel humanized IgG-4 mAb against programmed cell death protein 1 (PD-1), for NSCLC in a real-world setting in China. Methods: This retrospective study leveraged electronic health record (EHR) data collected during routine patient care in 8 cancer centers in China. The cohort included patients with mNSCLC who had received toripalimab for metastatic disease (n = 166) with > 1 EHR-documented visit from January, 2019, to June, 2020. Patients (age ≥ 18yrs) with pathologically or histologically diagnosed advanced NSCLC receiving toripalimab treatment were enrolled in this retrospective, multicenter, real-world study. The endpoints included progression-free survival (PFS), overall response rate (ORR), disease control rate (DCR) and duration of response (DOR). Results: Between January 2019 and June 2020, 166 patients from 8 centers were eligible. The median age was 60.6 years, 134(81.7%) male, 123(76.4%) diagnosed as stage IV lung cancer, 69(42.9%) squamous histology, 25 (21.9%) underwent prior surgery and 94 (57%) received prior chemotherapy. Toripalimab was administered as first, second, and further lines of therapy in 45(28.1%), 60(37.5%) and 55(34.4%) patients, respectively. Among them, 28(17.5%) patients received toripalimab as monotherapy. 22(13.8%) received in combination with antiangiogenic agent and 132(82.5%) in combination with chemotherapy. The 164 patients were eligible for efficacy evaluation. The ORR and DCR were 21.3% and 81.7% for all the evaluable patients. The median PFS was 15.0 months (95% CI 10.2 – NA). The median PFS of adenocarcinoma and squamous cell carcinoma were 15.4 months(95% CI 10.2-NA) and 13.4 months(95% CI 10.6-NA), respectively. The PFS in first line and further-line treatment were 15.4 months(95% CI 12.6-15.4) and 13.4 months(95% CI 7.0-NA). Stratified analysis revealed that the PFS of toripalimab monotherapy and combination treatment were 15.0 months(95% CI 12.6-15.0) and 15.4 months(95% CI 8-NA). The PFS were comparable between the patients received with or without anti-angiogenesis agents (11.5m vs 15.4m). Conclusions: Toripalimab monotherapy or in combination with chemotherapy and/or antiangiogenic agent in real world were effective in advanced NSCLC patients.

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