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Clinical Trial
. 2019 Jan 1;21(1):106-114.
doi: 10.1093/neuonc/noy091.

Safety and efficacy of depatuxizumab mafodotin + temozolomide in patients with EGFR-amplified, recurrent glioblastoma: results from an international phase I multicenter trial

Andrew B Lassman  1 , Martin J van den Bent  2 , Hui K Gan  3   4   5 , David A Reardon  6 , Priya Kumthekar  7 , Nicholas Butowski  8 , Zarnie Lwin  9 , Tom Mikkelsen  10 , Louis B Nabors  11 , Kyriakos P Papadopoulos  12 , Marta Penas-Prado  13 , John Simes  14 , Helen Wheeler  15 , Tobias Walbert  10 , Andrew M Scott  3   4   5 , Erica Gomez  16 , Ho-Jin Lee  16 , Lisa Roberts-Rapp  16 , Hao Xiong  16 , Peter J Ansell  16 , Earle Bain  16 , Kyle D Holen  16 , David Maag  16 , Ryan Merrell  17
Affiliations
Clinical Trial

Safety and efficacy of depatuxizumab mafodotin + temozolomide in patients with EGFR-amplified, recurrent glioblastoma: results from an international phase I multicenter trial

Andrew B Lassman et al. Neuro Oncol. .

Abstract

Background: Patients with glioblastoma (GBM) have a dismal prognosis. Nearly all will relapse with no clear standard of care for recurrent disease (rGBM). Approximately 50% of patients have tumors harboring epidermal growth factor receptor (EGFR) amplification. The antibody-drug conjugate depatuxizumab mafodotin (depatux-m) binds cells with EGFR amplification, is internalized, and releases a microtubule toxin, killing the cell. Here we report efficacy, safety and pharmacokinetics (PK) of depatux-m + temozolomide (TMZ) in patients with EGFR-amplified rGBM.

Methods: M12-356 (NCT01800695) was an open-label study encompassing patients with newly diagnosed or rGBM across 3 treatment arms. Results are reported for adults with EGFR-amplified, measurable rGBM who received depatux-m (0.5-1.5 mg/kg) on days 1 and 15, and TMZ (150-200 mg/m2) on days 1-5 in a 28-day cycle. Patients were bevacizumab and nitrosourea naïve.

Results: There were 60 patients, median age 56 years (range, 20-79). Fifty-nine patients previously received TMZ. Common adverse events (AEs) were blurred vision (63%), fatigue (38%), and photophobia (35%). Grades 3/4 AEs were split between ocular and non-ocular AEs, occurring in 22% of patients each. Systemic PK exposure of depatux-m was dose proportional. The objective response rate was 14.3%, the 6-month progression-free survival rate was 25.2%, and the 6-month overall survival rate was 69.1%.

Conclusions: Depatux-m + TMZ displayed an AE profile similar to what was described previously. Antitumor activity in this TMZ-refractory population was encouraging. Continued study of depatux-m in patients with EGFR-amplified, newly diagnosed, or recurrent GBM is ongoing in 2 global, randomized trials (NCT02573324, NCT02343406).

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Figures

Fig. 1
Fig. 1
Best response and time on therapy. The best responses as determined by the investigator using RANO criteria and time on depatux-m therapy are shown for 60/60 patients (analysis included 1 patient each with SD and PD without measurable disease at baseline).
Fig. 2
Fig. 2
Best percentage change in tumor size. The percent change in target lesion from baseline are shown for 56/58 patients who had measurable disease at baseline and at least one post-baseline measurement. Best tumor percent change is defined as the maximum reduction/minimum increase from baseline in tumor size. Values were determined per investigator measurements.
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References

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