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Clinical Trial
. 2020 May 15;22(5):684-693.
doi: 10.1093/neuonc/noz222.

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

Martin Van Den Bent  1 , Marica Eoli  2 , Juan Manuel Sepulveda  3 , Marion Smits  4 , Annemiek Walenkamp  5 , Jean-Sebastian Frenel  6 , Enrico Franceschi  7 , Paul M Clement  8 , Olivier Chinot  9 , Filip De Vos  10 , Nicolas Whenham  11 , Paul Sanghera  12 , Michael Weller  13 , H J Dubbink  14 , Pim French  1 , Jim Looman  15 , Jyotirmoy Dey  16   15 , Scott Krause  15 , Pete Ansell  15 , Sarah Nuyens  17 , Maarten Spruyt  1 , Joana Brilhante  17 , Corneel Coens  17 , Thierry Gorlia  17 , Vassilis Golfinopoulos  17
Affiliations
Clinical Trial

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

Martin Van Den Bent et al. Neuro Oncol. .

Erratum in

Abstract

Background: Depatuxizumab mafodotin (Depatux-M) is a tumor-specific antibody-drug conjugate consisting of an antibody (ABT-806) directed against activated epidermal growth factor receptor (EGFR) and the toxin monomethylauristatin-F. We investigated Depatux-M in combination with temozolomide or as a single agent in a randomized controlled phase II trial in recurrent EGFR amplified glioblastoma.

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: Two hundred sixty patients were randomized. In the primary efficacy analysis with 199 events (median follow-up 15.0 mo), the hazard ratio (HR) for the combination arm compared with 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 grades 3-4 adverse events 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).

Keywords: Antibody drug conjugate; EGFR; depatux-m; glioblastoma; recurrent.

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Figures

Fig. 1
Fig. 1
Consolidated Standards of Reporting Trials (CONSORT) flow diagram of EORTC study 1410, at the time of primary analysis.
Fig. 2
Fig. 2
(A) Overall survival (Kaplan–Meier) curve for the comparison between Depatux-M with temozolomide versus the control arm (lomustine or temozolomide) at the time of long-term follow-up. (B) Overall survival (Kaplan–Meier) curve for the comparison between Depatux-M monotherapy versus the control arm (lomustine or TMZ) at the time of long-term follow-up.
Fig. 2
Fig. 2
(A) Overall survival (Kaplan–Meier) curve for the comparison between Depatux-M with temozolomide versus the control arm (lomustine or temozolomide) at the time of long-term follow-up. (B) Overall survival (Kaplan–Meier) curve for the comparison between Depatux-M monotherapy versus the control arm (lomustine or TMZ) at the time of long-term follow-up.
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Comment in

References

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