Phase I study of anti-epidermal growth factor receptor antibody-drug conjugate serclutamab talirine: Safety, pharmacokinetics, and antitumor activity in advanced glioblastoma

Benedito A. Carneiro, Kyriakos P. Papadopoulos, John H. Strickler, Andrew B. Lassman, Saiama N. Waqar, Young Kwang Chae, Jyoti D. Patel, Einat Shacham-Shmueli, Karen Kelly, Mustafa Khasraw, Christine M. Bestvina, Ryan Merrell, Kevin Huang, Harisha Atluri, Peter Ansell, Rachel Li, Janet Jin, Mark G. Anderson, Edward B. Reilly, Gladys Morrison-ThieleKalpesh Patel, Randy R. Robinson, Martha R.Neagu Aristide, Hui K. Gan

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

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 the 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 a lack of efficacy (NCT03234712).

Original languageEnglish
Article numbervdac183
JournalNeuro-Oncology Advances
Volume5
Issue number1
DOIs
StatePublished - Jan 1 2023

Keywords

  • EGFR
  • antibody-drug conjugate
  • glioblastoma
  • phase I
  • serclutamab talirine

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