Caicun Zhou1, Lin Wu2, Yun Fan3, Zhehai Wang4, Lianke Liu5, Gongyan Chen6, Li Zhang7, Dingzhi Huang8, Shundong Cang9, Zhixiong Yang10, Jianying Zhou11, Chengzhi Zhou12, Baolan Li13, Juan Li14, Min Fan15, Jiuwei Cui16, Yuping Li17, Hui Zhao18, Jian Fang19, Jianxin Xue20, Chengping Hu21, Ping Sun22, Yingying Du23, Hui Zhou24, Shuyan Wang24, Wen Zhang24. 1. Oncology Department, Shanghai Pulmonary Hospital, Shanghai, People's Republic of China. Electronic address: caicunzhoudr@163.com. 2. Thoracic Medicine Department II, Hunan Cancer Hospital, Changsha, People's Republic of China. 3. Oncology Department, Cancer Hospital of the University of Chinese Academy of Science, Hangzhou, People's Republic of China. 4. Respiratory Department, Shandong Cancer Hospital, Jinan, People's Republic of China. 5. Oncology Department, Jiangsu Province Hospital, Nanjing, Country. 6. Respiratory Department, The Affiliated Tumor Hospital of Harbin Medical University, Harbin, People's Republic of China. 7. Respiratory Department, Chinese Academy of Medical Sciences & Peking Union Medical College, Guangzhou, People's Republic of China. 8. Lung Cancer Department, Tianjin Medical University Cancer Institute & Hospital, Tianjin, People's Republic of China. 9. Oncology Department, Henan Provincial Peoples Hospital, Zhengzhou, People's Republic of China. 10. Oncology Department, Affiliated Hospital of Guangdong Medical University, Zhanjiang, People's Republic of China. 11. Respiratory Department, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, People's Republic of China. 12. Oncology Department, The First Affiliate Hospital of Guangzhou Medical University, Guangzhou, People's Republic of China. 13. General medicine Department, Beijing Chest Hospital, Capital Medical University, Beijing, People's Republic of China. 14. Department of Thoracic Medical Oncology, Sichuan Cancer Hospital, Chengdu, People's Republic of China. 15. The Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai, People's Republic of China. 16. Oncology Department, The First Hospital of Jilin University, Changchun, People's Republic of China. 17. Department of Respiratory Medicine, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, People's Republic of China. 18. Department of Respiratory Medicine, The Second Hospital of Anhui Medical University, Hefei, People's Republic of China. 19. Department of Thoracic Oncology, Beijing Cancer Hospital, Beijing, People's Republic of China. 20. Department of Thoracic Oncology, West China Hospital, Sichuan University, Chengdu, People's Republic of China. 21. Respiratory Department, Xiangya Hospital Central South University, Changsha, People's Republic of China. 22. Oncology Department, Yantai Yuhuangding Hospital, Yantai, People's Republic of China. 23. Oncology Department, The First Affiliated Hospital of Anhui Medical University, Hefei, People's Republic of China. 24. Medical Science and Strategy Oncology, Innovent Biologics Inc., Suzhou, People's Republic of China.
Abstract
INTRODUCTION: The standard chemotherapy for squamous NSCLC (sqNSCLC) includes platinum plus gemcitabine. Sintilimab, an anti-programmed cell death protein 1 antibody, plus platinum and gemcitabine (GP) has revealed encouraging efficacy as first-line therapy for sqNSCLC in a phase 1b study. We conducted a randomized, double-blind, phase 3 study to further compare the efficacy and safety of sintilimab with placebo, both in combination with GP. METHODS: ORIENT-12, a randomized, double-blind, phase 3 study, was conducted at 42 centers in the People's Republic of China (ClinicalTrials.gov, number NCT03629925). Patients with locally advanced or metastatic sqNSCLC and without EGFR-sensitive mutations or ALK rearrangements were enrolled in the study. The stratification factors included clinical stage, choice of platinum, and programmed death-ligand 1 tumor proportion score. The patients, investigators, research staff, and sponsor team were masked to treatment assignment. Eligible patients were randomized 1:1, using an integrated web-response system, to receive sintilimab 200 mg or placebo plus GP every 3 weeks for four or six cycles, followed by sintilimab or placebo as maintenance therapy until disease progression or 2 years. The primary end point was progression-free survival (PFS), assessed by an independent radiographic review committee. RESULTS:Between September 25, 2018 and July 26, 2019, a total of 543 patients were screened, of whom 357 patients were randomized to the sintilimab-GP group (n = 179) and the placebo-GP group (n = 178). After a median follow-up period of 12.9 months, sintilimab-GP continued to reveal a meaningful improvement in PFS than placebo-GP (hazard ratio = 0.536 [95% confidence interval: 0.422-0.681], p < 0.00001). Treatment-emergent adverse events of grade 3 or worse occurred in 86.6% patients in the sintilimab-GP group and in 83.1% in the placebo-GP group. The incidence of treatment-emergent adverse event leading to death was 4.5% and 6.7% in the two treatment groups, respectively. CONCLUSIONS: Regarding PFS, sintilimab plus GP reveals clinical benefit than GP alone as first-line therapy in patients with locally advanced or metastatic sqNSCLC. The toxicity was acceptable, and no new unexpected safety signals were observed.
RCT Entities:
INTRODUCTION: The standard chemotherapy for squamous NSCLC (sqNSCLC) includes platinum plus gemcitabine. Sintilimab, an anti-programmed cell death protein 1 antibody, plus platinum and gemcitabine (GP) has revealed encouraging efficacy as first-line therapy for sqNSCLC in a phase 1b study. We conducted a randomized, double-blind, phase 3 study to further compare the efficacy and safety of sintilimab with placebo, both in combination with GP. METHODS: ORIENT-12, a randomized, double-blind, phase 3 study, was conducted at 42 centers in the People's Republic of China (ClinicalTrials.gov, number NCT03629925). Patients with locally advanced or metastatic sqNSCLC and without EGFR-sensitive mutations or ALK rearrangements were enrolled in the study. The stratification factors included clinical stage, choice of platinum, and programmed death-ligand 1 tumor proportion score. The patients, investigators, research staff, and sponsor team were masked to treatment assignment. Eligible patients were randomized 1:1, using an integrated web-response system, to receive sintilimab 200 mg or placebo plus GP every 3 weeks for four or six cycles, followed by sintilimab or placebo as maintenance therapy until disease progression or 2 years. The primary end point was progression-free survival (PFS), assessed by an independent radiographic review committee. RESULTS: Between September 25, 2018 and July 26, 2019, a total of 543 patients were screened, of whom 357 patients were randomized to the sintilimab-GP group (n = 179) and the placebo-GP group (n = 178). After a median follow-up period of 12.9 months, sintilimab-GP continued to reveal a meaningful improvement in PFS than placebo-GP (hazard ratio = 0.536 [95% confidence interval: 0.422-0.681], p < 0.00001). Treatment-emergent adverse events of grade 3 or worse occurred in 86.6% patients in the sintilimab-GP group and in 83.1% in the placebo-GP group. The incidence of treatment-emergent adverse event leading to death was 4.5% and 6.7% in the two treatment groups, respectively. CONCLUSIONS: Regarding PFS, sintilimab plus GP reveals clinical benefit than GP alone as first-line therapy in patients with locally advanced or metastatic sqNSCLC. The toxicity was acceptable, and no new unexpected safety signals were observed.