LTBK-04 FIRST RESULTS OF THE RANDOMIZED PHASE II STUDY ON DEPATUX –M ALONE, DEPATUX-M IN COMBINATION WITH TEMOZOLOMIDE AND EITHER TEMOZOLOMIDE OR LOMUSTINE IN RECURRENT EGFR AMPLIFIED GLIOBLASTOMA: FIRST REPORT FROM INTELLANCE 2/EORTC TRIAL 1410

Abstract

BACKGROUND

Depatux-m is a tumor-specific antibody-drug-conjugate consisting of antibody (ABT-806) bound to the toxin monomethylauristatin-F. We investigated depatux-m in EGFR-amplified recurrent glioblastoma (40–50% of glioblastoma).

METHODS

EORTC-1410-BTG (NCT02343406) is a randomized open label phase II study. Eligible were patients with centrally confirmed EGFR-amplified glioblastoma at first recurrence after temozolomide chemo-irradiation, occurring ≥3 months after radiotherapy. After stratification for WHO status and time of relapse (<16 or ≥16 weeks after the first day of the last temozolomide cycle), patients were randomized to either a) treatment with depatux-m 1.0 mg/kg every 2 weeks intravenously, or b) the same treatment combined with temozolomide 150–200 mg/m2 day 1–5 every 4 weeks, or c) either lomustine or temozolomide (TMZ/LOM) depending on the time of relapse. Primary endpoint was overall survival (OS); 240 patients/170 events were needed to detect a HR reduction of 0.54 in the depatux-m arms.

RESULTS

Between March 2015 and July 2016 260 patients were randomized. With 199 events observed, for the primary comparison of depatux-m in combination with TMZ versus TMZ/LOM a HR of 0.71 was observed (95%CI [0.50, 1.02]; p = 0.031 one-sided; median OS 9.6 months versus 8.2 months, 1-year OS rate 39.7% versus 28.2%). No OS difference was observed between depatux-m monotherapy (median OS 7.9 months) and TMZ/LOM (HR 1.04; 95%CI [0.73, 1.48]. In patients with relapse ≥16 weeks after end of 1stline TMZ treatment, combined depatux-m/TMZ was associated with improved OS (HR 0.45, 95%CI [0.23, 0.87]; median OS 14.9 months versus 9.5 months). The main toxicity observed in depatux-m treated patients was ocular (grade 3: 27.9%, grade 4: 1%).

CONCLUSION

Although the primary endpoint was not met, depatux-m in combination with TMZ might improve OS in EGFR amplified recurrent glioblastoma. Outcome for depatux-m monotherapy was similar to LOM/TMZ control. Ocular events observed were consistent with earlier studies.