Efficacy and safety of sintilimab plus pemetrexed and platinum as first-line treatment for locally advanced or metastatic nonsquamous non-small cell lung cancer: a randomized, double-blind, phase 3 study (ORIENT-11).

Yang, Yunpeng; Wang, Zhehai; Fang, Jian; Yu, Qitao; Han, Baohui; Cang, Shundong; Chen, Gongyan; Mei, Xiaodong; Yang, Zhixiong; Ma, Rui; Bi, Minghong; Ren, Xiubao; Zhou, Jianying; Li, Baolan; Song, Yong; Feng, Jifeng; Li, Juan; He, Zhiyong; Zhou, Rui; Li, Weimin; Lu, You; Wang, Yingyi; Wang, Lijun; Yang, Nong; Zhang, Yan; Yu, Zhuang; Zhao, Yanqiu; Xie, Conghua; Cheng, Ying; Zhou, Hui; Wang, Shuyan; Zhu, Donglei; Zhang, Wen; Zhang, Li

INTRODUCTION Sintilimab, an anti-programmed death 1 antibody, plus pemetrexed and platinum had shown promising efficacy for nonsquamous non-small cell lung cancer in a phase 1b study. We conducted a randomized, double-blind, phase 3 study to compare the efficacy and safety of sintilimab with placebo, both in combination with such chemotherapy. (ClinicalTrials.gov: NCT03607539) METHODS: A total of 397 patients with previously untreated locally advanced or metastatic nonsquamous NSCLC without sensitizing epidermal growth factor receptor or anaplastic lymphoma kinase genomic aberration were randomized (2:1 ratio) to receive either sintilimab 200 mg or placebo plus pemetrexed and platinum Q3W for 4 cycles, followed by sintilimab or placebo plus pemetrexed therapy. Crossover or treatment beyond disease progression was allowed. The primary endpoint was progression-free survival (PFS) by independent radiographic review committee. RESULTS As of Nov. 15, 2019, the median follow-up was 8.9 months. The median PFS was significantly longer in the sintilimab-combination group than that in the placebo-combination group (8.9 vs. 5.0 months; HR, 0.482, 95%CI, 0.362 to 0.643; p < 0.00001). The confirmed objective response rate was 51.9 % (95% CI, 45.7% to 58.0%) in sintilimab-combination group and 29.8% (95% CI, 22.1% to 38.4%) in placebo-combination group. The incidence of grade 3 or higher adverse events was 61.7% in sintilimab-combination group and 58.8% in placebo-combination group. CONCLUSIONS In Chinese patients with previously untreated locally advanced or metastatic nonsquamous NSCLC, the addition of sintilimab to chemotherapy of pemetrexed and platinum resulted in significantly longer PFS than that of chemotherapy alone with manageable safety profiles.