Clinical benefits were very close to those reported in the combination therapy arm in the previous phase 2 trial. To our knowledge, this is the first study to assess the role of Depatux-M plus TMZ in recurrent EGFR-amplified GBM patients in a real-life world. The Depatux-M toxicity profile was similar to the phase 1 study’s observed toxicities. Worth noting among patients treated with the combination regimen is that the benefit in OS was more consistent for those who relapsed/progressed more than 16 weeks after the start of the last cycle of TMZ. Although the study did not reach the primary endpoint of OS, at the time of long-term follow-up the combination arm demonstrated a statistically longer OS compared to the other arms. A subsequent phase 2 study was planned on the basis of this promising data: INTELLANCE 2/EORTC1410 (NCT02343406) was a multicenter, randomized open label study comparing Depatux-M plus TMZ (arm 1) versus Depatux-M alone (arm 2) versus standard treatment of TMZ/lomustine (arm 3/control arm) in EGFR-amplified GBM at first recurrence/progression after standard chemoradiotherapy. The combination arm showed interesting results in the recurrent GBM population, with an objective response rate of 14.3% and a 6-month OS of 69.1%.
TYPESTATUS PLUS FREE TRIAL
Depatux-M was initially evaluated in the phase 1 M12-356 (NCT01800695) trial this study analyzed the safety, preliminary efficacy and pharmacokinetics of Depatux-M alone or in combination with TMZ in patients with newly-diagnosed or recurrent GBM. After interaction with the tumor-specific binding site (exposed and available in the case of EGFR amplification), Depatux-M is internalized in the cell and mafodotin is released, thus killing the cell.
Toxicity was moderate and manageable.ĭepatuxizumab Mafodotin (Depatux-M ABT-414) is an antibody-drug conjugate composed of the anti-EGFR monoclonal antibody conjugated to monomethyl auristatin F (mafodotin), an antimicrotubule agent. Overall, the results are close to those reported in the previous phase 2 trial. Encouraging clinical benefits were demonstrated, even though most patients were treated beyond second-line therapy. Conclusions: The study reported the first “real world” experience of Depatux-M plus temozolomide in recurrent glioblastoma patients. No death was considered to be drug-related. Grade 3 ocular toxicity occurred in 11% of patients no grade 4 ocular toxicity was reported. On univariate and multivariate analyses, the MGMT methylation status was the only factor resulting significantly associated with survival. The median age was 57 years, ECOG PS was 0–1 in 28 patients (88%), MGMT methylated status was found in 22 (64%), 15 patients (42%) received the combined treatment as second-line therapy. Results: A total of 36 patients were enrolled. The primary endpoints of the study were overall survival and safety. According to the original schedule, patients received Depatux-M 1.25 mg/kg every 2 weeks combined with temozolomide. The major inclusion criteria were: histologically confirmed diagnosis of glioblastoma, EGFR-amplified, one or more prior systemic therapies and ECOG PS ≤ 2. Materials and Methods: Patients were enrolled from seven AINO (Italian Association of Neuro-Oncology) Institutions. For the first time worldwide, our work investigated the clinical outcome and safety of this combination in a real-life population. The INTELLANCE 2/EORTC 1410 phase 2 trial produced interesting results for the combination regimen of Depatux-M and temozolomide in EGFR-amplified glioblastoma patients at first recurrence. Background: Depatuxizumab Mafodotin (Depatux-M ABT-414) is an antibody-drug conjugate consisting of a specific antibody against activated EGFR and a cytotoxic agent with antimicrotubule activity.
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