TY - JOUR
T1 - Safety and efficacy of depatuxizumab mafodotin in Japanese patients with malignant glioma
T2 - A nonrandomized, phase 1/2 trial
AU - Narita, Yoshitaka
AU - Muragaki, Yoshihiro
AU - Kagawa, Naoki
AU - Asai, Katsunori
AU - Nagane, Motoo
AU - Matsuda, Masahide
AU - Ueki, Keisuke
AU - Kuroda, Junichiro
AU - Date, Isao
AU - Kobayashi, Hiroyuki
AU - Kumabe, Toshihiro
AU - Beppu, Takaaki
AU - Kanamori, Masayuki
AU - Kasai, Shota
AU - Nishimura, Yasuko
AU - Xiong, Hao
AU - Ocampo, Christopher
AU - Yamada, Masakazu
AU - Mishima, Kazuhiko
N1 - Funding Information:
AbbVie sponsored the study, contributed to its design, and participated in the collection, analysis, and interpretation of the data and in the writing, reviewing, and approval of the manuscript. All authors had access to all relevant data and participated in writing, review, and approval of this manuscript. No honoraria or payments were made for authorship. This study was funded by AbbVie, Inc., North Chicago, IL. Medical writing support was provided by Chun Zhou, PhD, of Fishawack Communications Ltd., funded by AbbVie. 0‒14 days max EGFRvIII
Publisher Copyright:
© 2021 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.
PY - 2021/12
Y1 - 2021/12
N2 - 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).
AB - 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).
KW - Anti–epidermal growth factor receptor therapy
KW - depatuxizumab mafodotin
KW - malignant glioma
KW - recurrent glioblastoma
KW - temozolomide
UR - http://www.scopus.com/inward/record.url?scp=85118388881&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85118388881&partnerID=8YFLogxK
U2 - 10.1111/cas.15153
DO - 10.1111/cas.15153
M3 - Article
C2 - 34609773
AN - SCOPUS:85118388881
SN - 1347-9032
VL - 112
SP - 5020
EP - 5033
JO - Cancer Science
JF - Cancer Science
IS - 12
ER -
