Safety and efficacy of depatuxizumab mafodotin in Japanese patients with malignant glioma: A nonrandomized, phase 1/2 trial,Cancer Science

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Safety and efficacy of depatuxizumab mafodotin in Japanese patients with malignant glioma: A nonrandomized, phase 1/2 trial
Cancer Science ( IF 4.5 ) Pub Date : 2021-10-05 , DOI: 10.1111/cas.15153
Yoshitaka Narita ₁ , Yoshihiro Muragaki ₂ , Naoki Kagawa ₃ , Katsunori Asai ₄ , Motoo Nagane ₅ , Masahide Matsuda ₆ , Keisuke Ueki ₇ , Junichiro Kuroda ₈ , Isao Date ₉ , Hiroyuki Kobayashi ₁₀ , Toshihiro Kumabe ₁₁ , Takaaki Beppu ₁₂ , Masayuki Kanamori ₁₃ , Shota Kasai ₁₄ , Yasuko Nishimura ₁₄ , Hao Xiong ₁₅ , Christopher Ocampo ₁₅ , Masakazu Yamada ₁₆ , Kazuhiko Mishima ₁₇

Affiliation

Department of Neurosurgery and Neuro-Oncology, National Cancer Center Hospital, Tokyo, Japan.
Department of Neurosurgery, Tokyo Women's Medical University Hospital, Tokyo, Japan.
Department of Neurosurgery, Osaka University Hospital, Osaka, Japan.
Department of Neurosurgery, Osaka International Cancer Institute, Osaka, Japan.
Faculty of Medicine, Department of Neurosurgery, Kyorin University, Tokyo, Japan.
Department of Neurosurgery, University of Tsukuba, Ibaraki, Japan.
Department of Neurosurgery, Dokkyo Medical University Hospital, Tochigi, Japan.
Department of Neurosurgery, Kumamoto University Hospital, Kumamoto, Japan.
Department of Neurosurgery, Okayama University Hospital, Okayama, Japan.
Department of Neurosurgery, Hokkaido University Hospital, Hokkaido, Japan.
Department of Neurosurgery, Kitasato University Hospital, Kanagawa, Japan.
Department of Neurosurgery, Iwate Medical University Hospital, Iwate, Japan.
Department of Neurosurgery, Tohoku University Hospital, Miyagi, Japan.
AbbVie GK., Tokyo, Japan.
AbbVie Inc., North Chicago, Illinois, USA.
Department of Ophthalmology, Kyorin University Hospital, Tokyo, Japan.
Department of Neuro-Oncology/Neurosurgery, International Medical Center, Saitama Medical University, Saitama, Japan.

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).

中文翻译：

depatuxizumab mafodotin 在日本恶性胶质瘤患者中的安全性和有效性：一项非随机、1/2 期试验

INTELLANCE-J 是一项针对表皮生长因子受体 (EGFR) depatuxizumab mafodotin (Depatux-M) 的强效抗体-药物偶联物作为二线或一线治疗的 1/2 期研究，单独或与化疗或53 例日本世界卫生组织 (WHO) III/IV 级胶质瘤患者的放化疗。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 加化疗（替莫唑胺）或单独 Depatux-M，无论 EGFR 状态如何。在一线治疗组中，新诊断的 WHO III/IV 级胶质瘤患者接受了 Depatux-M 加放化疗。在全球试验 INTELLANCE-1 中，由于缺乏一线 Depatux-M 的生存获益，该研究被停止。主要终点是接受二线 Depatux-M 联合化疗的 EGFR 扩增肿瘤患者的 6 个月无进展生存期 (PFS)。二线和一线 Depatux-M 的常见非眼部治疗出现的不良事件 (TEAE) 包括淋巴细胞减少（分别为 42%、33%）、血小板减少（39%、47%）、丙氨酸转氨酶升高（29%， 47%)，天冬氨酸转氨酶增加 (24%, 60%)；≥3 级 TEAE 的发生率分别为 66% 和 53%。93% 接受二线 Depatux-M 加化疗的患者和所有接受二线 Depatux-M 单独或一线 Depatux-M 加放化疗的患者发生眼部副作用 (OSE)。大多数 OSE 可以通过剂量调整和伴随药物控制。6 个月 PFS 估计值为 25.6%（95% 置信区间 [CI] 11.4-42.6），在 EGFR 扩增亚组中，二线 Depatux-M 加化疗的中位 PFS 为 2.1 个月（95% CI 1.9-3.9）。该研究显示，在日本 WHO III/IV 级胶质瘤患者中，单独使用 Depatux-M 或联合化疗/放化疗的安全性是可接受的。该研究已在 ClinicalTrials.gov (NCT02590263) 上注册。

更新日期：2021-12-06

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