17P Safety and tolerability of sintilimab (sint) combination therapy in patients with advanced or recurrent non-small cell lung cancer (NSCLC): Pooled safety analysis of ORIENT 11 and ORIENT 12 studies

Abstract

Sint has shown efficacy in randomized, double-blind, phase 3 studies in Chinese patients with NSCLC in ORIENT 11 and ORIENT 12. To further address the safety profile of sint, we present pooled safety and tolerability data from both studies. ORIENT 11 enrolled (2:1) patients with advanced/metastatic nonsquamous NSCLC to receive either sint 200 mg or placebo (pbo) + pemetrexed + platinum once every 3 weeks. ORIENT 12 enrolled (1:1) patients with advanced/metastatic squamous NSCLC to receive either sint 200 mg or pbo + gemcitabine + platinum every 3 weeks. The designs and eligibility of both studies were similar. Pooled analyses were to support the safety assessments by summarizing treatment-related adverse events (TRAE), immune-related TRAE (ir-TRAE) and the association of ir-TRAE with efficacy. Of 754 patients pooled from two studies (ORIENT 11, n=397; ORIENT 12, n=357), 445 were pooled to the sint arm, and 309 to the pbo arm. There were no meaningful differences in baseline characteristics between subjects with or without ir-TRAE in both arms. The TRAE rates were comparable (sint vs pbo: 85.8% vs 81.6%) between the two arms. Although sint arm had higher ir-TRAE occurrence than pbo arm (sint vs pbo: 42.5% vs 30.7%), ≥ Grade 3 ir-TRAE were comparable in both arms (sint vs pbo: 6.1% vs 4.9%). Notably, higher ir-TRAEs were found in sint arm in rash, hypothyroidism, and immune-mediated pneumonitis. TRAE leading to drug discontinuation (sint vs pbo: 6.5% vs 4.2%) and death (sint vs pbo: 0.9% vs 2.3%) are comparable between the two arms. The exploratory analysis indicated that patients experienced ir-TRAE showed longer PFS and OS than those without ir-TRAE in sint arm (Table).Table: 17PEfficacy subgroup analysis by ir-TRAE status in sint armEndpointssint Patients withNEvents, n (%)Median (95%CI), monthHazard ratio (95% CI)Between-group p-value (two-sided)PFSir-TRAE18991 (48.1%)9.0 (6.8, 10.9)0.65 (0.51, 0.82)<0.01no ir-TRAE256148 (57.8%)6.9 (6.0, 7.2)OSir-TRAE18940 (21.2%)NR (NR, NR)0.64 (0.46, 0.90)0.01no ir-TRAE25676 (29.7%)14.9 (13.8, NR)NR= Not Reached Note: Median and 95% CI are estimated based on unstratified Kaplan-Meier method. Hazard ratio and p-value are estimated using a stratified time-dependent Cox proportional hazard regression model. Open table in a new tab NR= Not Reached Note: Median and 95% CI are estimated based on unstratified Kaplan-Meier method. Hazard ratio and p-value are estimated using a stratified time-dependent Cox proportional hazard regression model. Sint in combination with chemotherapy demonstrated a tolerable and manageable safety profile in Chinese patients, generally consistent with the pbo population in ORIENT 11 and ORIENT 12 study.