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

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).

• Authors: 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
• Journal: Neuro-oncology (Neuro Oncol) Vol. 22 Issue 5 Pg. 684-693 (05 15 2020) ISSN: 1523-5866 [Electronic] England
• PMID: 31747009 (Publication Type: Clinical Trial, Phase II, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: © The Author(s) 2019. Published by Oxford University Press on behalf of the Society for Neuro-Oncology.

Chemical References

• Antibodies, Monoclonal, Humanized
• Antineoplastic Agents, Alkylating
• Lomustine
• EGFR protein, human
• ErbB Receptors
• depatuxizumab mafodotin
• Temozolomide

Topics

• Antibodies, Monoclonal, Humanized
• Antineoplastic Agents, Alkylating (therapeutic use)
• Brain Neoplasms (drug therapy)
• ErbB Receptors (genetics)
• Glioblastoma (drug therapy)
• Humans
• Lomustine (therapeutic use)
• Temozolomide (therapeutic use)