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, Marica Eoli, Juan Manuel Sepulveda, Marion Smits, Annemiek Walenkamp, Jean-Sebastian Frenel, Enrico Franceschi, Paul M Clement, Olivier Chinot, Filip De Vos, Nicolas Whenham, Paul Sanghera, Michael Weller, H J Dubbink, Pim French, Jim Looman, Jyotirmoy Dey, Scott Krause, Pete Ansell, Sarah Nuyens, Maarten Spruyt, Joana Brilhante, Corneel Coens, Thierry Gorlia, Vassilis Golfinopoulos, Martin Van Den Bent, Marica Eoli, Juan Manuel Sepulveda, Marion Smits, Annemiek Walenkamp, Jean-Sebastian Frenel, Enrico Franceschi, Paul M Clement, Olivier Chinot, Filip De Vos, Nicolas Whenham, Paul Sanghera, Michael Weller, H J Dubbink, Pim French, Jim Looman, Jyotirmoy Dey, Scott Krause, Pete Ansell, Sarah Nuyens, Maarten Spruyt, Joana Brilhante, Corneel Coens, Thierry Gorlia, Vassilis Golfinopoulos

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.

© The Author(s) 2019. Published by Oxford University Press on behalf of the Society for Neuro-Oncology.

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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