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

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

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).