Phase 1b trial of anti-EGFR antibody JMT101 and Osimertinib in EGFR exon 20 insertion-positive non-small-cell lung cancer.
Phase 1b trial of anti-EGFR antibody JMT101 and Osimertinib in EGFR exon 20 insertion-positive non-small-cell lung cancer.
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DOI：
10.1038/s41467-023-39139-4
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发表时间：
2023-06-12
影响因子：
16.6
通讯作者：
Fang, Wenfeng
中科院分区：
文献类型：
--
作者：
Zhao, Shen;Zhuang, Wu;Han, Baohui;Song, Zhengbo;Guo, Wei;Luo, Feng;Wu, Lin;Hu, Yi;Wang, Huijuan;Dong, Xiaorong;Jiang, Da;Wang, Mingxia;Miao, Liyun;Wang, Qian;Zhang, Junping;Fu, Zhenming;Huang, Yihua;Xu, Chunwei;Hu, Longyu;Li, Lei;Hu, Rong;Yang, Yang;Li, Mengke;Yang, Xiugao;Zhang, Li;Huang, Yan;Fang, Wenfeng
EGFR 外显子 20 插入 (20ins) 阳性非小细胞肺癌 (NSCLC) 是一种罕见疾病，治疗选择有限且预后不佳。在这里，我们报告了临床前模型和开放标签、多中心 1b 期试验 (NCT04448379) 联合 JMT101（抗 EGFR 单克隆抗体）加奥希替尼的双重靶向 EGFR 20ins 的活性、耐受性、潜在反应机制和耐药性。试验的主要终点是耐受性。次要终点包括客观缓解率、缓解持续时间、疾病控制率、无进展生存期、总体生存期、JMT101的药代动力学特征、抗药物抗体的出现以及生物标志物与临床结果之间的相关性。共有 121 名患者入组接受 JMT101 加奥希替尼 160mg 治疗。最常见的不良事件是皮疹（76.9%）和腹泻（63.6%）。确认的客观缓解率为36.4%。中位无进展生存期为 8.2 个月。未达到中位反应持续时间。根据临床病理学特征和既往治疗进行亚组分析。在铂类难治性疾病患者（n = 53）中，确认的客观缓解率为34.0%，中位无进展生存期为9.2个月，中位缓解持续时间为13.3个月。在不同的 20ins 变异和颅内病变中观察到反应。颅内疾病控制率为87.5%。确认颅内客观缓解率为25%。具有 EGFR 外显子 20 插入的非小细胞肺癌 (NSCLC) 患者对早期 EGFR 酪氨酸激酶抑制剂 (TKI) 具有耐药性。在这里，作者报告了 I 期临床试验 JMT101（一种抗 EGFR 抗体）与 EGFR-TKI、阿法替尼或奥希替尼联合治疗 NSCLC 患者的安全性和初步疗效。
EGFR exon 20 insertion (20ins)-positive non-small-cell lung cancer (NSCLC) is an uncommon disease with limited therapeutic options and dismal prognosis. Here we report the activity, tolerability, potential mechanisms of response and resistance for dual targeting EGFR 20ins with JMT101 (anti-EGFR monoclonal antibody) plus osimertinib from preclinical models and an open label, multi-center phase 1b trial (NCT04448379). Primary endpoint of the trial is tolerability. Secondary endpoints include objective response rate, duration of response, disease control rate, progression free survival, overall survival, the pharmacokinetic profile of JMT101, occurrence of anti-drug antibodies and correlation between biomarkers and clinical outcomes. A total of 121 patients are enrolled to receive JMT101 plus osimertinib 160 mg. The most common adverse events are rash (76.9%) and diarrhea (63.6%). The confirmed objective response rate is 36.4%. Median progression-free survival is 8.2 months. Median duration of response is unreached. Subgroup analyses were performed by clinicopathological features and prior treatments. In patients with platinum-refractory diseases (n = 53), confirmed objective response rate is 34.0%, median progression-free survival is 9.2 months and median duration of response is 13.3 months. Responses are observed in distinct 20ins variants and intracranial lesions. Intracranial disease control rate is 87.5%. Confirmed intracranial objective response rate is 25%. Patients with non-small cell lung cancer (NSCLC) with EGFR exon 20 insertions are resistant to early generation EGFR tyrosine kinase inhibitors (TKI). Here, the authors report the safety and preliminary efficacy of a phase I clinical trial JMT101, an anti-EGFR antibody, combined with EGFR-TKI, afatinib or osimertinib, in patients with NSCLC.
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影响因子：
30.8
作者：
Blakely CM;Watkins TBK;Wu W;Gini B;Chabon JJ;McCoach CE;McGranahan N;Wilson GA;Birkbak NJ;Olivas VR;Rotow J;Maynard A;Wang V;Gubens MA;Banks KC;Lanman RB;Caulin AF;St John J;Cordero AR;Giannikopoulos P;Simmons AD;Mack PC;Gandara DR;Husain H;Doebele RC;Riess JW;Diehn M;Swanton C;Bivona TG
通讯作者：
Bivona TG
影响因子：
8.4
作者：
Eisenhauer, E. A.;Therasse, P.;Verweij, J.
通讯作者：
Verweij, J.
影响因子：
14.9
作者：
Forbes, Simon A.;Tang, Gurpreet;Futreal, P. Andrew
通讯作者：
Futreal, P. Andrew
DOI：
10.1093/bioinformatics/btp698
发表时间：
2010-03-01
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Li H;Durbin R
通讯作者：
Durbin R
影响因子：
64.8
作者：
Jia Y;Yun CH;Park E;Ercan D;Manuia M;Juarez J;Xu C;Rhee K;Chen T;Zhang H;Palakurthi S;Jang J;Lelais G;DiDonato M;Bursulaya B;Michellys PY;Epple R;Marsilje TH;McNeill M;Lu W;Harris J;Bender S;Wong KK;Jänne PA;Eck MJ
通讯作者：
Eck MJ