First-Line Treatment of Advanced Non-Small-Cell Lung Cancer With Negative Driver Gene: a Multicenter, Single-Arm Trial

Summary

To evaluate the efficacy and safety of recombinant human endostatin (Endostar) combined with platinum-based doublet chemotherapy as the first-line therapy for patients with driver-gene-negative advanced non-small cell lung cancer(NSCLC). This study is an exploratory single-arm study. The specific treatment regimen is as follows: Non-squamous NSCLC: Endostar (210 mg, continuous intravenous infusion (CIV) for 120 h) is started on the first day of each treatment cycle and administered every three weeks. Carboplatin AUC 5-6 mg/ml/min or cisplatin 75 mg/m2 (d4) +pemetrexed 500 mg/m2 (d4) Q3W is administered in this regimen for 4 cycles followed by Endostar plus pemetrexed until disease progression or intolerable toxicity. Squamous NSCLC: Endostar (210 mg, continuous intravenous infusion (CIV) for 120 hours) is started on the first day of each treatment cycle and administered every three weeks. Carboplatin AUC 5-6 mg/ml/min or cisplatin 75 mg/m2 (d4) + paclitaxel 175 mg/m2 (d4) Q3W.Endostar is administered after 4 cycles of this treatment regimen until disease progression or intolerable toxicity developed. Patients are assessed for measurable disease at baseline, 6 weeks, 12 weeks after starting treatment, and every 9 weeks thereafter according to RECIST 1.1 criteria during the treatment period until disease progression or intolerable toxicity withdrawal. Following discontinuation of treatment, subjects are followed for survival status every 3 months until death. Subject safety was assessed during treatment according to NCI CTCAE Version 4.0 criteria. Subjects who experience an AE should be followed until the AE returns to baseline. The primary endpoints is Progression-free survival (PFS) . Secondary endpoints include objective response rate (ORR), overall survival (OS) and safety (NCI CTCAE v 4.0). Statistical methods: The PFS curve was estimated using the Kaplan-Meier method for the largest population to be analyzed. The confidence interval method was used as the criterion for the main analysis. OS was calculated in the same way as the secondary endpoint. Descriptive statistics will be used to analyze ORR, DCR, etc. It is expected that continuous intravenous Endostar combined with platinum-based doublet chemotherapy as first-line treatment will prolong median PFS and OS in patients with driver gene-negative advanced NSCLC.

Timeline

Start

2021-02-01

Primary completion

2024-02-01

Completion

2024-04-01

Publications

• Results Mok TS, Wu YL, Thongprasert S, Yang CH, Chu DT, Saijo N, Sunpaweravong P, Han B, Margono B, Ichinose Y, Nishiwaki Y, Ohe Y, Yang JJ, Chewaskulyong B, Jiang H, Duffield EL, Watkins CL, Armour AA, Fukuoka M. Gefitinib or carboplatin-paclitaxel in pulmonary adenocarcinoma. N Engl J Med. 2009 Sep 3;361(10):947-57. doi: 10.1056/NEJMoa0810699. Epub 2009 Aug 19.
• Results Rinaldi M, Cauchi C, Gridelli C. First line chemotherapy in advanced or metastatic NSCLC. Ann Oncol. 2006 May;17 Suppl 5:v64-7. doi: 10.1093/annonc/mdj953.
• Results Wang J, Sun Y, Liu Y, Yu Q, Zhang Y, Li K, Zhu Y, Zhou Q, Hou M, Guan Z, Li W, Zhuang W, Wang D, Liang H, Qin F, Lu H, Liu X, Sun H, Zhang Y, Wang J, Luo S, Yang R, Tu Y, Wang X, Song S, Zhou J, You L, Wang J, Yao C. [Results of randomized, multicenter, double-blind phase III trial of rh-endostatin (YH-16) in treatment of advanced non-small cell lung cancer patients]. Zhongguo Fei Ai Za Zhi. 2005 Aug 20;8(4):283-90. doi: 10.3779/j.issn.1009-3419.2005.04.07. Chinese.
• Results Zhai Y, Ma H, Hui Z, Zhao L, Li D, Liang J, Wang X, Xu L, Chen B, Tang Y, Wu R, Xu Y, Pang Q, Chen M, Wang L. HELPER study: A phase II trial of continuous infusion of endostar combined with concurrent etoposide plus cisplatin and radiotherapy for treatment of unresectable stage III non-small-cell lung cancer. Radiother Oncol. 2019 Feb;131:27-34. doi: 10.1016/j.radonc.2018.10.032. Epub 2018 Dec 17.
• Results Hansma AH, Broxterman HJ, van der Horst I, Yuana Y, Boven E, Giaccone G, Pinedo HM, Hoekman K. Recombinant human endostatin administered as a 28-day continuous intravenous infusion, followed by daily subcutaneous injections: a phase I and pharmacokinetic study in patients with advanced cancer. Ann Oncol. 2005 Oct;16(10):1695-701. doi: 10.1093/annonc/mdi318. Epub 2005 Jul 12.
• Liu X, Guo Z, Su L, Zuo A, Gao M, Ji X, Lu J, Yang S, Jiang Y, Lu D. The efficacy and safety of continuous intravenous infusion of rh-endostatin combined with platinum-based doublet chemotherapy for advanced non-small-cell lung cancer. Invest New Drugs. 2024 Jun;42(3):309-317. doi: 10.1007/s10637-024-01439-x. Epub 2024 May 3.

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