4月13日，百時美施貴寶公布Opdivo（Nivolumab）在中國肺癌患者中開展的CheckMate-078（NCT02613507，CTR20150767）最新臨床試驗數(shù)據(jù)，相比多西他賽，Opdivo能夠使中國經(jīng)治非小細胞肺癌患者總生存期顯著獲益（HR 0.68，p=0.0006），結(jié)果也會在4月16日于AACR2018年會上口頭報告。目前，百時美施貴寶的Nivolumab，默沙東帕博利珠單抗和君實生物特瑞普利單抗處于中國PD-(L)1抗體上市第一梯隊，百時美施貴寶Opdivo很大概率成為首個登陸中國的PD-(L)1抗體。

       一．3款PD-(L)1抗體審評進度更新

       2017年11月1日，百時美施貴寶率先提交nivolumab中國上市申請，正式啟動中國上市進程，預(yù)計在2018年下半年正式獲批。

       目前，根據(jù)CDE官方信息，Nivolumab注射液2017年11月1日進入CDE，已完成藥理毒理和臨床數(shù)據(jù)審評，藥學處于待審評狀態(tài)。默沙東帕博利珠單抗和君實生物特瑞普利單抗先后進入CDE，處于"排隊待審評"狀態(tài)。

       二．經(jīng)治NSCLC：CheckMate-078臨床試驗全部數(shù)據(jù)公布

       2017年11月30日，百時美施貴寶便公布了獨立數(shù)據(jù)監(jiān)測委員會關(guān)于CheckMate-078的分析結(jié)果，臨床試驗達到總生存期主要終點，提前完成試驗。

       CheckMate-078是一項主要在中國人群開展的臨床3期、隨機、多中心的臨床試驗，評估Nivolumab對比多西他賽治療既往接受過治療的晚期或轉(zhuǎn)移性非小細胞安全性和有效性。對應(yīng)的臨床受理號為JXSL1300032。

       CheckMate-078表明，相比多西他賽，Opdivo能夠使中國經(jīng)治非小細胞肺癌患者總生存期顯著獲益（HR 0.68，p=0.0006），并能夠降低疾病進展風險，獲得具有統(tǒng)計學意義的臨床收益，這與CheckMate-017和CheckMate-057總生存期數(shù)據(jù)保持一致。

       另外，在各個基于組織學分型和PD-L1水平的不同亞組分析中，Opdivo能夠延長各個亞組患者的總生存期，具體數(shù)據(jù)見下表：

       附加資料：

       1. 部分CheckMate系列試驗信息匯總：

       CheckMate相關(guān)試驗總計約80項，下表中列出了幾個比較重要的CheckMate臨床試驗信息：

       2. AACR2018-checkmate-078 口頭報告信息一覽

       ##Session CTMS02 - Updates in Immuno-oncology Trials

       CT114 - Nivolumab versus docetaxel in a predominantly Chinese patient population with previously treated advanced non-small cell lung cancer (NSCLC): results of the phase 3 CheckMate 078 study

       Webcast Status

       Webcast Available May 9

       Presenter/Authors

       Y-L. Wu1, S. Lu2, Y. Cheng3, C. Zhou4, J. Wang5, T. Mok6, L. Zhang7, H. Tu1, L. Wu8, J. Feng9, Y. Zhang10, A. V. Luft11, J. Zhou12, Z. Ma13, Y. Lu14, C. Hu15, Y. Shi16, C. Baudelet17, Z. Li17, J. Chang18; 1Guandong Gen. Hosp., Guangzhou, China, 2Shanghai Lung Cancer Ctr., Shanghai Chest Hosp., Shanghai JiaoTong Univ., Shanghai, China, 3Jilin Cancer Hosp., Changchun, China, 4Shanghai Pulmonary Hosp., Shanghai, China, 5Chinese Academy of Med. Sci., Beijing, China, 6Chinese Univ. of Hong Kong, Shatin, Hong Kong, 7Sun Yat-Sen Univ., Guangzhou, China, 8Hunan Cancer Hosp., Changsha, China, 9Jiangsu Cancer Hosp., Beijing, China, 10Zhejiang Cancer Hosp., Hangzhou, China, 11Leningrad Regional Clinical Hosp., Leningrad, Russian Federation, 12First Affiliated Hosp., Coll. of Med., Zhejiang Univ., Hangzhou, China, 13Henan Cancer Hosp., Zhengzhou, China, 14West China Hosp., Chengdu, China, 15Xiangya Hosp., Central South Univ., Changsha, China, 16Natl. Cancer Ctr./Cancer Hosp., Chinese Academy of Med. Sci. and Peking Union Med. Coll., Beijing, China, 17Bristol-Myers Squibb, Princeton, NJ, 18Fudan Univ. Shanghai Cancer Ctr., Shanghai, China

       Disclosures

       Y. Wu: ; AstraZeneca. ; Roche. ; Eli Lilly. ; Pfizer. ; Sanofi. S. Lu: None. Y. Cheng: None. C. Zhou: None. J. Wang: ; Non-financial support; AstraZeneca. T. Mok: ; AstraZeneca, Roche/Genentech, Bristol-Myers Squibb, Boehringer Ingelheim, Novartis, MSD, Pfizer. ; Eli Lilly, Takeda. ; Merck Serono, Vertex, ACEA Biosciences, Oncogenex, Celgene, Ignyta Inc, Fishawack Facilitate Ltd, Janssen, ChiMed. ; Clovis Oncology, SFJ Pharmaceuticals. ; Uncompensated; geneDecode. ; Eisai. ; Taiho. L. Zhang: None. H. Tu:None. L. Wu: None. J. Feng: None. Y. Zhang: None. A.V. Luft: None. J. Zhou: None. Z. Ma: None. Y. Lu: None. C. Hu: None. Y. Shi: None. C. Baudelet: ; Bristol-Myers Squibb. Z. Li: ; Bristol-Myers Squibb. J. Chang: None.

       Abstract

       Introduction: Lung cancer incidence in China has increased and it remains the leading cause of cancer death, highlighting a need for new treatments. We report results from CheckMate 078, the first phase 3 study of an anti-programmed death (ligand) 1 (PD-[L]1) agent in predominantly Chinese patients with NSCLC and disease progression after platinum (Pt)-based chemotherapy.

       Methods: Patients who had disease progression during or after Pt-based doublet chemotherapy were randomized 2:1 to receive nivolumab (3 mg/kg Q2W) or docetaxel (75 mg/m2 Q3W). Patients were included regardless of tumor histology or PD-L1 expression, and randomization was stratified according to both of these factors (≥1% vs <1%/unevaluable tumor PD-L1; squamous vs non-squamous histology). Patients with epidermal growth factor receptor mutation-positive tumors were excluded. The primary endpoint was overall survival (OS); other endpoints included progression-free survival (PFS) and objective response rate (ORR).

       Results: 639 patients were enrolled from December 2015 to December 2016; 504 were randomized. Of all randomized patients, ~90% were from China, 60% had non-squamous tumor histology; tumor PD-L1 expression was <1% in 41% of patients and ≥1% in 50% of patients (9% unevaluable). Minimum follow-up was 8.8 months. OS was significantly improved with nivolumab (n=338) vs docetaxel (n=166); median OS was 12.0 vs 9.6 months, respectively (hazard ratio [HR; 97.7% CI]: 0.68 [0.52, 0.90]; P<0.001). The HR (95% CI) for OS was 0.61 (0.42, 0.89) in patients with squamous NSCLC and 0.76 (0.56, 1.04) in patients with non-squamous NSCLC. In patients with tumor PD-L1 expression <1% and ≥1%, the HR (95% CI) was 0.75 (0.52, 1.09) and 0.62 (0.45, 0.87), respectively. Median PFS was 2.8 months in both treatment arms; PFS curves began to separate at 3 months, resulting in a PFS advantage with nivolumab (HR [95% CI]: 0.77 [0.62, 0.95]; P=0.0147). ORR was 17% with nivolumab vs 4% with docetaxel; median duration of response was not reached with nivolumab (95% CI: 11.1 months, not available [NA]) and 5.3 (95% CI: 3.58, NA) months with docetaxel. Rates of grade ≥3 treatment-related adverse events were lower among patients treated with nivolumab (10%) vs docetaxel (48%).

       Conclusions: In this population of patients with advanced NSCLC previously treated with Pt-based chemotherapy, nivolumab demonstrated superior OS, PFS, and ORR compared with docetaxel. Efficacy and safety of nivolumab in this first randomized controlled trial of nivolumab in NSCLC in a predominantly Chinese patient population were consistent with the results of the pivotal global CheckMate 017/057 studies.

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