Afatinib in paediatric patients with recurrent/refractory ErbB-dysregulated tumours: Results of a phase I/expansion trial

This phase I/expansion study assessed the safety, pharmacokinetics and preliminary antitumor activity of afatinib in paediatric patients with cancer. The dose-finding part enroled patients (2–0). The primary end-points were dose-limiting toxicities (DLTs), afatinib exposure, and objective response. Of 564 patients pre-screened, 536 patients had biomarker data and 63 (12%) fulfilled ≥2 EGFR/HER2 criteria required for inclusion in the expansion part. A total of 56 patients were treated (17 in the dose-finding and 39 in the expansion part). DLTs were observed in one of six MTD-evaluable patients receiving 18 mg/m²/d and in two of five MTD-evaluable patients receiving 23 mg/m²/d; 18 mg/m²/d was defined as the MTD. There were no new safety signals. Pharmacokinetics confirmed exposure consistent with the approved dose in adults. One partial response (−81% per Response Assessment in Neuro-Oncology) was observed in a patient with a glioneuronal tumour harbouring a CLIP2::EGFR fusion; unconfirmed partial responses were observed in two patients. In total, 25% of patients experienced objective response or stable disease (95% confidence interval: 14–38). Targetable EGFR/HER2 drivers are rare in paediatric cancers. Treatment with afatinib led to a durable response (>3 years) in one patient with a glioneuronal tumour with CLIP2::EGFR fusion. •12% of 536 paediatric patients screened had ≥2 potential ErbB-activation markers.•56 paediatric patients with ErbB-dysregulated tumours received afatinib.•MTD in children was 18 mg/m²/d; PK and safety were equivalent to adults.•Objective response observed in one patient (>3 years), with a CLIP2::EGFR fusion.•EGFR gene fusion or driver mutations are rare in paediatric cancer but are sensitive to afatinib.