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Sugemalimab versus placebo after concurrent or sequential chemoradiotherapy in patients with locally advanced, unresectable, stage III non-small-cell lung cancer in China (GEMSTONE-301): interim results of a randomised, double-blind, multicentre, phase 3 trial Qing Zhou 1, Ming Chen 2, Ou Jiang 3, Yi Pan 1, Desheng Hu 4, Qin Lin 5, Gang Wu 6, Jiuwei Cui 7, Jianhua Chang 8, Yufeng Cheng 9, Cheng Huang 10, Anwen Liu 11, Nong Yang 12, Youling Gong 13, Chuan Zhu 14, Zhiyong Ma 15, Jian Fang 16, Gongyan Chen 17, Jun Zhao 16, Anhui Shi 16, Yingcheng Lin 18, Guanghui Li 19, Yunpeng Liu 20, Dong Wang 21, Rong Wu 22, Xinhua Xu 23, Jianhua Shi 24, Zhihua Liu 25, Na Cui 26, Jingru Wang 26, Qiang Wang 26, Ran Zhang 26, Jason Yang 26, Yi-Long Wu 27 Background: A substantial proportion of patients with unresectable stage III non-small-cell lung cancer (NSCLC) cannot either tolerate or access concurrent chemoradiotherapy, so sequential chemoradiotherapy is commonly used. We assessed the efficacy and safety of sugemalimab, an anti-PD-L1 antibody, in patients with stage III NSCLC whose disease had not progressed after concurrent or sequential chemoradiotherapy. Methods: GEMSTONE-301 is a randomised, double-blind, placebo-controlled, phase 3 trial in patients with locally advanced, unresectable, stage III NSCLC, done at 50 hospitals or academic research centres in China. Eligible patients were aged 18 years or older with an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 who had not progressed after concurrent or sequential chemoradiotherapy. We randomly assigned patients (2:1, using an interactive voice-web response system) to receive sugemalimab 1200 mg or matching placebo, intravenously every 3 weeks for up to 24 months. Stratification factors were ECOG performance status, previous chemoradiotherapy, and total radiotherapy dose. The investigators, trial coordination staff, patients, and study sponsor were masked to treatment allocation. The primary endpoint was progression-free survival as assessed by blinded independent central review (BICR) in the intention-to-treat population. Safety was assessed in all participants who received at least one dose of assigned study treatment. The study has completed enrolment and the results of a preplanned analysis of the primary endpoint are reported here. The trial is registered with ClinicalTrials.gov, NCT03728556. Findings: Between Aug 30, 2018 and Dec 30, 2020, we screened 564 patients of whom 381 were eligible. Study treatment was received by all patients randomly assigned to sugemalimab (n=255) and to placebo (n=126). At data cutoff (March 8, 2021), median follow-up was 14·3 months (IQR 6·4-19·4) for patients in the sugemalimab group and 13·7 months (7·1-18·4) for patients in the placebo group. Progression-free survival assessed by BICR was significantly longer with sugemalimab than with placebo (median 9·0 months [95% CI 8·1-14·1] vs 5·8 months [95% CI 4·2-6·6]; stratified hazard ratio 0·64 [95% CI 0·48-0·85], p=0·0026). Grade 3 or 4 treatment-related adverse events occurred in 22 (9%) of 255 patients in the sugemalimab group versus seven (6%) of 126 patients in the placebo group, the most common being pneumonitis or immune-mediated pneumonitis (seven [3%] of 255 patients in the sugemalimab group vs one [<1%] of 126 in the placebo group). Treatment-related serious adverse events occurred in 38 (15%) patients in the sugemalimab group and 12 (10%) in the placebo group. Treatment-related deaths were reported in four (2%) of 255 patients (pneumonia in two patients, pneumonia with immune-mediated pneumonitis in one patient, and acute hepatic failure in one patient) in the sugemalimab group and none in the placebo group. Interpretation: Sugemalimab after definitive concurrent or sequential chemoradiotherapy could be an effective consolidation therapy for patients with stage III NSCLC whose disease has not progressed after sequential or concurrent chemoradiotherapy. Longer follow-up is needed to confirm this conclusion. 研究设计：这是一项随机、双盲、安慰剂对照的III期非小细胞肺癌患者，患者年龄PS评分2:1的比例随机分为舒格利单抗或安慰剂治疗24个月PS评分、放疗与化疗的顺序以及放疗的剂量进行分层。主要研究终点为独立评审委员会评估的255例和14.3个月和IIIa期患者两组中位10.5个月和HR=0.74；PFS分别为5.8个月，IIIc期的患者，两组中位8.6个月和HR=0.73。同步放化疗患者，两组中位10.5个月和HR=0.66，序贯放化疗的患者，两组中位8.1个月和HR=0.59。
9%和3%和＜15%和2%和III期非小细胞肺癌患者，接受同步或序贯放化疗后给予舒格利单抗维持治疗可改善患者预后，但这一结论需要长期随访数据的确认。
参考文献 Zhou Q, Chen M, Jiang O, Pan Y, Hu D, Lin Q, Wu G, Cui J, Chang J, Cheng Y, Huang C, Liu A, Yang N, Gong Y, Zhu C, Ma Z, Fang J, Chen G, Zhao J, Shi A, Lin Y, Li G, Liu Y, Wang D, Wu R, Xu X, Shi J, Liu Z, Cui N, Wang J, Wang Q, Zhang R, Yang J, Wu YL. Sugemalimab versus placebo after concurrent or sequential chemoradiotherapy in patients with locally advanced, unresectable, stage III non-small-cell lung cancer in China (GEMSTONE-301): interim results of a randomised, double-blind, multicentre, phase 3 trial. Lancet Oncol. 2022 Feb;23(2):209-219. doi: 10.1016/S1470-2045(21)00630-6. Epub 2022 Jan 14. PMID: 35038429.
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