Summary
A single-site phase 1 trial evaluated D2C7-ATC, an EGFR-targeted antibody-toxin conjugate, in recurrent malignant glioma. Among 72 patients with IDH-wild-type recurrent glioblastoma, median overall survival was 7.9 months.
A single-site phase 1 trial published in Nature Medicine evaluated D2C7-ATC, an antibody-toxin conjugate designed to target wild-type EGFR and the mutant receptor EGFRvIII, in recurrent malignant glioma. Among 72 patients with IDH-wild-type recurrent glioblastoma, median overall survival was 7.9 months. The study’s primary aims were to assess toxicity and identify a recommended phase 2 dose; it was not designed to compare survival with another treatment.
How D2C7-ATC was delivered
The study enrolled 81 people with biopsy-confirmed recurrent malignant glioma. Each received a single infusion of D2C7-ATC into the enhancing disease using convection-enhanced delivery (CED). CED uses pressure-driven infusion to move a drug through tissue in the brain. The antibody component of an antibody-toxin conjugate is designed to recognise a target—in this case, EGFR or EGFRvIII—while carrying a toxin.
The trial was open-label, single-arm and conducted at one site. In the dose-escalation stage, 35 patients with IDH-wild-type recurrent glioblastoma received concentrations ranging from 40 to 35,032 ng/mL. A further 37 patients were treated in the dose-expansion stage at the recommended phase 2 dose (RP2D) of 6,920 ng/mL.
Safety and survival findings
The researchers reported that treatment-related adverse events were mainly grade 1–2 (67%). At 35,032 ng/mL, the maximum tolerated dose was exceeded: four patients experienced dose-limiting toxicities, including two grade 4 and two grade 3 events. Eight patients died during the trial; the authors judged those deaths unrelated to D2C7-ATC.
Across the 72 patients with IDH-wild-type recurrent glioblastoma, median overall survival was 7.9 months. This is an outcome observed among treated patients, not a measure of how much longer they lived because of the therapy: the single-arm design had no comparison group and was primarily intended to establish safety and dosing.
The team also reported survival associations in univariate analyses. Patients whose pretreatment tumours had a D2C7 antibody reactivity score below 1.5+ had a median overall survival of 17.38 months. Patients with low IL-8 in plasma after treatment had a median of 16.6 months. These estimates refer to separate biomarker-defined groups, and the analyses identify associations rather than showing that either marker caused a better outcome.
The findings provide a phase 1 safety and dosing assessment for an EGFR-directed therapy delivered directly into recurrent brain tumours. The recommended dose and biomarker associations can inform further clinical research, while the study design means its survival results should be interpreted as descriptive rather than comparative evidence of benefit.