ESMO 2018 – Synthetic peptides hit three targets simultaneously in recurrent glioblastoma


  • Michael Simm
  • Oncology Conference reports
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Takeaway

  • SL-701 is a synthetic peptide that targets three molecules overexpressed in glioblastoma: IL-13Rα2, Ephrin A2, and survivin.
  • It is administered subcutaneously every two weeks with costimulants, resulting in activation of CD8+ T cells.
  • When given with bevacizumab, it showed low toxicity and disease control for at least 8 weeks in up to 54% of patients with 2 CRs of 22 weeks and 46 weeks duration, and a median OS of 11.7 months.

Why this matters

  • The targeting of multiple molecules with one agent is an innovative approach for glioblastoma, that may add to the efficiency of established agents.

Key results

  • Among 74 patients treated, most frequent adverse events were fatigue (22%) and injection site reaction (18%), with only two grade 3 incidents (fatigue).
  • Disease control rate (CR+PR+SD≥8 weeks) was 22% in stage 1 and increased to 54% with the change of adjuvant and addition of bevacizumab.
  • 12-month overall survival (OS) was 44% in stage 1 and 50% in stage 2. Median OS was 11 months in stage 1 and 11.7 months in stage 2.

Study design

  • Bevacicumab-naïve patients with HLA-A2+ recurrent glioblastoma and KPS>60 received SL-701 in stage 1 with adjuvants GM-CSF and imiquimod biweekly for 6 months, then q28 days.
  • For stage 2, poly-ICLC was chosen as adjuvant and biweekly bevacicumab (10 mg/kg) was added for 6 months, then q28 days. Safety, 12-month OS, and SL-701-specific CD8+ T cells were assessed.

Limitations

  • Small sample, uncontrolled.

Funding

  • Stemline Therapeutics.

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