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Neuro Oncol. 2019 Nov 20. pii: noz222. doi: 10.1093/neuonc/noz222. [Epub ahead of print]

INTELLANCE 2/EORTC 1410 randomized phase II study of Depatux-M alone and with temozolomide vs temozolomide or lomustine in recurrent EGFRamplified glioblastoma.

Author information

1
Brain Tumor Institute Erasmus MC Cancer Institute, Rotterdam NL.
2
dept neurology, Istituto Neurologico Carlo Besta Milano It.
3
Hospital Universitario 12 de Octubre Madrid ES.
4
dept Radiology, Erasmus MC , Rotterdam, the Netherlands.
5
Dept Medical Oncology, UMCG, University of Groningen, Groningen, the Netherlands.
6
Dept Medical Oncology, Centre R Gauducheau, Nantes France.
7
Dept Medical Oncology, AUSL-IRCCS Scienze Neurologiche, Bologna Italy.
8
Dept Medical Oncology, Leuven Cancer Institute, KU Leuven, Belgium.
9
Aix-Marseille Univ, APHM, CNRS, INP, Inst Neurophysiopathol, CHU Timone, Service de Neuro-Oncologie, Marseille, France.
10
Dept medical Oncology, UMCU Utrecht, the Netherlands.
11
Dept Medical Oncology, St Luc, Brussels, Belgium.
12
University Hospitals Birmingham, Birmingham GB (7) OK.
13
Dept Neurology, University Hospital Zurich, Switzerland.
14
Dept Pathology, Erasmus MC Cancer Institute H.J. Dubbink.
15
Dept Neurology Erasmus MC University Medical Center Rotterdam NL.
16
AbbVie, Il, Chicago, USA.
17
EORTC Headquarters, Brussels, Belgium.

Abstract

BACKGROUND:

Depatux-M is a tumor-specific antibody-drug-conjugate consisting of an antibody (ABT-806) directed against the activated Epithelial Growth Factor Receptor (EGFR) and the toxin monomethylauristatin-F. We investigated Depatux-M in combination with temozolomide or as single agent in a randomized controlled phase II trial in recurrent EGFR amplified glioblastoma.

PATIENTS AND METHODS:

Eligible were patients with centrally confirmed EGFR amplified glioblastoma at first recurrence after chemo-irradiation with temozolomide. Patients were randomized to either Depatux-M 1.25 mg/kg every 2 weeks intravenously, or this treatment combined with temozolomide 150-200 mg/m2 day 1-5 every 4 weeks, or either lomustine or temozolomide. The primary endpoint of the study was overall survival.

RESULTS:

260 patients were randomized. In the primary efficacy analysis with 199 events (median follow-up 15.0 months) the hazard ratio (HR) for the combination arm compared to the control arm was 0.71, 95% CI [0.50, 1.02]; p = 0.062. The efficacy of Depatux-M monotherapy was comparable to that of the control arm (HR =1.04, 95%CI [0.73, 1.48]; p = 0.83). The most frequent toxicity in Depatux-M treated patients was a reversible corneal epitheliopathy, occurring as grade 3-4 in 25-30% of patients. In the long-term follow-up analysis with median follow-up of 28,7 months the HR for the comparison of the combination arm versus the control arm was 0.66 (95%CI [0.48, 0.93].

CONCLUSION:

This trial suggests a possible role for the use of Depatux-M in combination with temozolomide in EGFR amplified recurrent glioblastoma, especially in patients relapsing well after the end of first-line adjuvant temozolomide treatment. (NCT02343406).

PMID:
31747009
DOI:
10.1093/neuonc/noz222

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