Phase 1 Trial Evaluates D2C7-ATC in Recurrent Malignant Glioma

D2C7-ATC targets wild-type EGFR and EGFRvIII. In this single-arm, single-site, open-label phase 1 trial, 81 patients with biopsy-confirmed recurrent malignant glioma received a single infusion into enhancing disease by convection-enhanced delivery. The primary objectives were to assess toxicity and determine the recommended phase 2 dose; secondary objectives included overall survival and its association with EGFR expression.

Among 72 patients with IDH-wild-type recurrent glioblastoma, median overall survival was 7.9 months. Treatment-related adverse events were mainly grade 1–2 (67%). At the highest dose, 35,032 ng ml−1, four patients had dose-limiting toxicities: two grade 4 and two grade 3. Eight patients died during the trial; the deaths were reported as unrelated to D2C7-ATC. Exploratory univariate analyses found survival associations with tumor antibody reactivity and other tumor, blood and plasma markers. The reported survival differences in biomarker-defined groups require confirmation.

The findings inform early-phase safety and dosing evaluation, but the uncontrolled design cannot show that D2C7-ATC prolongs survival. The biomarker findings are exploratory and do not establish a basis for selecting patients in clinical practice.