Open AccessSafety and efficacy of depatuxizumab mafodotin in Japanese patients with malignant glioma: A nonrandomized, phase 1/2 trial
Author(s) -
Narita Yoshitaka,
Muragaki Yoshihiro,
Kagawa Naoki,
Asai Katsunori,
Nagane Motoo,
Matsuda Masahide,
Ueki Keisuke,
Kuroda Junichiro,
Date Isao,
Kobayashi Hiroyuki,
Kumabe Toshihiro,
Beppu Takaaki,
Kanamori Masayuki,
Kasai Shota,
Nishimura Yasuko,
Xiong Hao,
Ocampo Christopher,
Yamada Masakazu,
Mishima Kazuhiko
Publication year - 2021
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/cas.15153
Subject(s) - temozolomide , medicine , glioma , chemotherapy , adverse effect , phases of clinical research , chemoradiotherapy , gastroenterology , concomitant , hazard ratio , surgery , oncology , confidence interval , cancer research
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).