369MO - Final results of depatuxizumab mafodotin plus temozolomide in recurrent glioblastoma patients: Real-world experience from a multicenter study of Italian Association of Neuro-Oncology (AINO)

Background

Precision medicine is a promising tool in oncology. DepatuxM is a new antibody-drug conjugate, consisting of a specific antibody against activated EGFR and a cytotoxic agent with antimicrotubule activity. The Intellance2/EORTC 1410 phase-II trial, showed interesting results for DepatuxM + TMZ combination in EGFRamplified glioblastoma patients at first recurrence after RT and TMZ. In our study, we investigated clinical outcome and safety of this combination used in recurrent GBM PTS as “compassionate use”.

Methods

PTS were enrolled from 7 centres of AINO and followed prospectively. Major inclusion criteria were: histologically confirmed diagnosis of GBM, 1 or more prior systemic therapies, ECOG PS ≤ 2 and EGFRamplified (FISH). Patients received DepatuxM 1.25 mg/kg every two weeks + TMZ until disease progression or unacceptable toxicity. Kaplan-Meier method was used to estimate the survival curves, RANO criteria for radiological assessment, CTCAE v5.0 for drug related adverse events.

Results

From October 2018 to June 2019, we enrolled 36 PTS: median age was 57, ECOG PS 0-1 in 88% of PTS, MGMTmet in 64%, 42% received the treatment as second line therapy. At the time of analysis, 24 PTS (67%) had died and 31 PTS (86%) had progressed. Median OS was 8.04ms (95%CI 5.3-10.7), 12m OS was 37%; medianPFS was 2.1ms (95% CI 1.7-2.4), 6ms PFS was 38%. All PTS were evaluable for response: disease control rate was 47%: stable disease was reported in 36%, partial response in 11% and complete response in 3% of PTS. Drug-related adverse events led to dose reductions of DepatuxM in 17% of PTS, in 28% was delayed and in 5% was permanently discontinued. Grade 3 ocular toxicity occurred in 11% of patients, no grade 4 ocular toxicity was reported; no death was considered drug-related.

Conclusions

We report the first “real world” experience of DepatuxM + TMZ in recurrent GBM. We showed encouraging clinical benefit, despite most patients were treated beyond the second-line of therapy. Overall, the results are closed to those reported in previous phase II trial. Toxicity was moderate and manageable. This combination would be re-considered as a potential treatment for this setting of patients.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.