Phase I Study of Anti-EGFR Antibody-Drug Conjugate Serclutamab Talirine: Safety, Pharmacokinetics, and Antitumor Activity in Advanced Glioblastoma

Abstract Background Serclutamab talirine (Ser-T, formerly ABBV-321) is an antibody-drug conjugate consisting of an antibody (AM-1-ABT-806) directed against activated epidermal growth factor receptor (EGFR) and a pyrrolobenzodiazepine dimer. We investigated Ser-T monotherapy in a phase I, first-in-human, dose-escalation and dose-expansion study in patients with advanced solid tumors associated with EGFR overexpression. Methods Eligible patients (≥18 years) had advanced, histologically confirmed solid tumors associated with EGFR overexpression (centralized testing). Patients received Ser-T intravenously once every 4 weeks (Q4W; 5–50 μg/kg) in the dose-escalation phase. Herein, preliminary antitumor activity at the recommended phase II dose (RP2D) is reported only for patients with glioblastoma (n=24); additional assessments included all treated patients. Results Sixty-two patients (median age: 58 years) were enrolled within dose-escalation (n=43) and dose-expansion (n=19) phases. One dose-limiting toxicity, grade 3 aspartate aminotransferase and alanine aminotransferase elevation, occurred at 20 μg/kg during dose-escalation. The Ser-T RP2D regimen of 50 μg/kg × 1 (loading dose) followed by 25 μg/kg Q4W (maintenance dose) was administered during dose-expansion. Fatigue (37%) was the only treatment-emergent adverse event (AE) occurring in >25% of patients. Two patients (3%) reported mild treatment-related ocular AEs (eye pruritus). Responses in patients with glioblastoma included 1 partial response (~33 months), 6 stable disease, and 14 progressive disease (not evaluable: n=3). Conclusions Ser-T monotherapy at doses up to 50 μg/kg initial dose, followed by 25 μg/kg Q4W demonstrated a tolerable safety profile with minimal antitumor activity observed in patients with glioblastoma. The glioblastoma dose-expansion cohort was closed due to lack of efficacy (NCT03234712).