Zhijie Wang1, Jun Zhao2, Zhiyong Ma3, Jiuwei Cui4, Yongqian Shu5, Zhe Liu6, Ying Cheng7, Shiang J Leaw8, Yanjie Wu8, Yan Ma8, Wei Tan8, Xiaopeng Ma8, Yun Zhang8, Jie Wang9. 1. State Key Laboratory of Molecular Oncology, Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China. 2. Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education, Beijing), Department of Thoracic Medical Oncology, Peking University Cancer Hospital & Institute, Beijing, China. 3. The Affiliated Cancer Hospital of Zhengzhou University/Henan Cancer Hospital, Zhengzhou, China. 4. The First Hospital of Jilin University, Changchun, China. 5. Jiangsu Province Hospital, Nanjing, China. 6. Beijing Chest Hospital, Capital Medical University, Beijing, China. 7. Jilin Cancer Hospital, Changchun, China. 8. BeiGene (Beijing) Co., Ltd., Beijing, China. 9. State Key Laboratory of Molecular Oncology, Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China. Electronic address: zlhuxi@163.com.
Abstract
OBJECTIVES: This phase 2 study explored tislelizumab, an anti-PD-1 antibody, in combination with platinum-based chemotherapy as first-line treatment of advanced lung cancer. MATERIAL AND METHODS: Eligible patients had histologically/cytologically confirmed advanced/metastatic nonsquamous non-small cell lung cancer (NSQ), squamous NSCLC (SQ), or extensive-stage small cell lung cancer (SCLC). All patients received tislelizumab 200 mg in combination with 4-6 cycles of platinum-doublet. The NSQ cohort received pemetrexed + platinum Q3W for 4 cycles followed by pemetrexed maintenance, the SQ cohort received paclitaxel + platinum (A) or gemcitabine + platinum (B) Q3W, and the SCLC cohort received etoposide + platinum Q3W. The primary endpoint was investigator-assessed objective response rate (ORR) per RECIST v1.1. Progression-free survival (PFS) and tolerability profile were secondary endpoints; exploratory endpoints included overall survival (OS) and predictive biomarkers. RESULTS: Fifty-four patients (NSQ, n = 16; SQ = 21 [SQ-A, n = 15; SQ-B, n = 6]; SCLC, n = 17) were enrolled; as of February 25, 2019, 14 remained on treatment. Confirmed ORRs were 44% (NSQ), 80% (SQ-A), 67% (SQ-B), and 77% (SCLC). Median PFS were 9.0 months (NSQ), 7.0 months (SQ-A), and 6.9 months (SCLC); PFS in SQ-B are not mature. Median OS was not reached in all cohorts except for SCLC (15.6 months). Common treatment-emergent AEs included anemia (79.6%, n = 43) and decreased white blood cell count (74.1%, n = 40). Gene expression analyses revealed distinct patterns by histology type; lower tumor inflammation signature levels were observed among nonresponding patients with NSQ and SCLC. CONCLUSIONS: Tislelizumab plus chemotherapy demonstrated encouraging antitumor activity, was generally well tolerated, and distinct immune- and cell cycle-related gene signatures were associated with efficacy across cohorts.
OBJECTIVES: This phase 2 study explored tislelizumab, an anti-PD-1 antibody, in combination with platinum-based chemotherapy as first-line treatment of advanced lung cancer. MATERIAL AND METHODS: Eligible patients had histologically/cytologically confirmed advanced/metastatic nonsquamous non-small cell lung cancer (NSQ), squamous NSCLC (SQ), or extensive-stage small cell lung cancer (SCLC). All patients received tislelizumab 200 mg in combination with 4-6 cycles of platinum-doublet. The NSQ cohort received pemetrexed + platinum Q3W for 4 cycles followed by pemetrexed maintenance, the SQ cohort received paclitaxel + platinum (A) or gemcitabine + platinum (B) Q3W, and the SCLC cohort received etoposide + platinum Q3W. The primary endpoint was investigator-assessed objective response rate (ORR) per RECIST v1.1. Progression-free survival (PFS) and tolerability profile were secondary endpoints; exploratory endpoints included overall survival (OS) and predictive biomarkers. RESULTS: Fifty-four patients (NSQ, n = 16; SQ = 21 [SQ-A, n = 15; SQ-B, n = 6]; SCLC, n = 17) were enrolled; as of February 25, 2019, 14 remained on treatment. Confirmed ORRs were 44% (NSQ), 80% (SQ-A), 67% (SQ-B), and 77% (SCLC). Median PFS were 9.0 months (NSQ), 7.0 months (SQ-A), and 6.9 months (SCLC); PFS in SQ-B are not mature. Median OS was not reached in all cohorts except for SCLC (15.6 months). Common treatment-emergent AEs included anemia (79.6%, n = 43) and decreased white blood cell count (74.1%, n = 40). Gene expression analyses revealed distinct patterns by histology type; lower tumor inflammation signature levels were observed among nonresponding patients with NSQ and SCLC. CONCLUSIONS:Tislelizumab plus chemotherapy demonstrated encouraging antitumor activity, was generally well tolerated, and distinct immune- and cell cycle-related gene signatures were associated with efficacy across cohorts.