Safety and efficacy of depatuxizumab mafodotin in Japanese patients with malignant glioma: A nonrandomized, phase 1/2 trial.
Safety and efficacy of depatuxizumab mafodotin in Japanese patients with malignant glioma: A nonrandomized, phase 1/2 trial.
复制标题
DOI：
10.1111/cas.15153
复制
发表时间：
2021-12
期刊：
影响因子：
5.7
通讯作者：
Mishima K
中科院分区：
文献类型：
--
作者：
Narita Y;Muragaki Y;Kagawa N;Asai K;Nagane M;Matsuda M;Ueki K;Kuroda J;Date I;Kobayashi H;Kumabe T;Beppu T;Kanamori M;Kasai S;Nishimura Y;Xiong H;Ocampo C;Yamada M;Mishima K
INTELLANCE-J是一项在53例世界卫生组织（WHO）III/IV级胶质瘤日本患者中开展的I/II期研究，研究靶向表皮生长因子受体（EGFR）的强效抗体-药物偶联物depatuxizumab mafodotin（Depatux-M）作为二线或一线治疗，单独使用或与化疗或放化疗联合使用。在二线治疗组中，EGFR扩增的复发性WHO III/IV级胶质瘤患者接受Depatux-M+化疗（替莫唑胺）或Depatux-M单药治疗，无论EGFR状态如何。在一线治疗组中，新诊断的WHO III/IV级胶质瘤患者接受Depatux-M加放化疗。在全球试验INTELLANCE-1中，由于一线Depatux-M缺乏生存获益，该研究停止。主要终点是接受二线Depatux-M+化疗的EGFR扩增肿瘤患者的6个月无进展生存期（PFS）。Depatux-M二线和一线治疗的常见非眼部治疗后出现的不良事件（TEAE）包括淋巴细胞减少症（分别为42%，33%）、血小板减少症（39%，47%）、丙氨酸氨基转移酶升高（29%，47%）和天冬氨酸氨基转移酶升高（24%，60%）; ≥3级TEAE的发生率分别为66%和53%。93%接受二线Depatux-M+化疗的患者和所有接受二线Depatux-M单药或一线Depatux-M+放化疗的患者发生了眼部副作用（OSE）。大多数OSE可通过剂量调整和合并用药进行管理。在EGFR扩增亚组中，二线Depatux-M联合化疗的6个月PFS估计值为25.6%（95%置信区间[CI] 11.4 ~ 42.6），中位PFS为2.1个月（95% CI 1.9 ~ 3.9）。本研究显示，Depatux-M单药或联合化疗/放化疗在WHO III/IV级胶质瘤日本患者中的安全性可接受。该研究在ClinicalTrials.gov（NCT 02590263）上注册。INTELLANCE-J是一项针对表皮生长因子受体（EGFR）的强效抗体药物偶联物（depatuxizumab mafodotin）作为二线或一线治疗（单独使用或与化疗或放化疗联合使用）治疗世界卫生组织III/IV级胶质瘤日本患者的I/II期研究。该试验的结果证明了departuxizumab mafodotin的可接受的安全性特征，眼部副作用是最常见的不良事件，大多数是可逆的。二线departuxizumab mafodotin联合替莫唑胺治疗EGFR扩增肿瘤患者的6个月无进展生存期估计值为25.6%（95%置信区间11.4 - 42.6），在该患者亚组中显示出令人鼓舞的抗肿瘤活性（NCT 02590263）。
INTELLANCE‐J was a phase 1/2 study of a potent antibody‐drug conjugate targeting epidermal growth factor receptor (EGFR), depatuxizumab mafodotin (Depatux‐M), as a second‐ or first‐line therapy, alone or combined with chemotherapy or chemoradiotherapy in 53 Japanese patients with World Health Organization (WHO) grade III/IV glioma. In second‐line arms, patients with EGFR‐amplified recurrent WHO grade III/IV glioma received Depatux‐M plus chemotherapy (temozolomide) or Depatux‐M alone regardless of EGFR status. In first‐line arms, patients with newly diagnosed WHO grade III/IV glioma received Depatux‐M plus chemoradiotherapy. The study was halted following lack of survival benefit with first‐line Depatux‐M in the global trial INTELLANCE‐1. The primary endpoint was 6‐month progression‐free survival (PFS) in patients with EGFR‐amplified tumors receiving second‐line Depatux‐M plus chemotherapy. Common nonocular treatment‐emergent adverse events (TEAEs) with both second‐line and first‐line Depatux‐M included lymphopenia (42%, 33%, respectively), thrombocytopenia (39%, 47%), alanine aminotransferase increase (29%, 47%), and aspartate aminotransferase increase (24%, 60%); incidence of grade ≥3 TEAEs was 66% and 53%, respectively. Ocular side effects (OSEs) occurred in 93% of patients receiving second‐line Depatux‐M plus chemotherapy and all patients receiving second‐line Depatux‐M alone or first‐line Depatux‐M plus chemoradiotherapy. Most OSEs were manageable with dose modifications and concomitant medications. The 6‐month PFS estimate was 25.6% (95% confidence interval [CI] 11.4‒42.6), and median PFS was 2.1 months (95% CI 1.9‒3.9) with second‐line Depatux‐M plus chemotherapy in the EGFR‐amplified subgroup. This study showed acceptable safety profile of Depatux‐M alone or plus chemotherapy/chemoradiotherapy in Japanese patients with WHO grade III/IV glioma. The study was registered at ClinicalTrials.gov (NCT02590263). INTELLANCE‐J was a phase 1/2 study of a potent antibody‐drug conjugate targeting epidermal growth factor receptor (EGFR), depatuxizumab mafodotin, as a second‐ or first‐line therapy, alone or combined with chemotherapy or chemoradiotherapy in Japanese patients with World Health Organization grade III/IV glioma. The results of this trial demonstrate an acceptable safety profile of depatuxizumab mafodotin, with ocular side effects being the most common adverse events that were mostly reversible. Second‐line depatuxizumab mafodotin in combination with temozolomide resulted in a 6‐month progression‐free survival estimate of 25.6% (95% confidence interval 11.4‒42.6) in patients with EGFR‐amplified tumors and showed encouraging antitumor activity in this subgroup of patients (NCT02590263).
登录
查看更多内容
影响因子：
158.5
作者：
Stupp, R;Mason, WP;Ryan, G
通讯作者：
Ryan, G
影响因子：
21.1
作者：
Shergalis A;Bankhead A 3rd;Luesakul U;Muangsin N;Neamati N
通讯作者：
Neamati N
DOI：
10.1073/pnas.1219817110
发表时间：
2013-01-02
影响因子：
11.1
作者：
Choi, Bryan D.;Kuan, Chien-Tsun;Sampson, John H.
通讯作者：
Sampson, John H.
影响因子：
50.5
作者：
Neyns, B.;Sadones, J.;De Greve, J.
通讯作者：
De Greve, J.
影响因子：
15.9
作者：
Lamborn, Kathleen R.;Yung, W. K. Alfred;Prados, Michael D.
通讯作者：
Prados, Michael D.