The tumor-targeting immunocytokine F16-IL2 in combination with doxorubicin: Dose escalation in patients with advanced solid tumors and expansion into patients with metastatic breast cancer

Chiara Catania, Michela Maur, Rossana Berardi, Andrea Rocca, Anna Maria Di Giacomo, Gianluca Spitaleri, Cristina Masini, Chiara Pierantoni, Reinerio González-Iglesias, Giulia Zigon, Annaelisa Tasciotti, Leonardo Giovannoni, Valeria Lovato, Giuliano Elia, Hans D. Menssen, Dario Neri, Stefano Cascinu, Pier Franco Conte, Filippo De Braud

Research output: Contribution to journalArticle

Abstract

A phase Ib/II trial was performed to evaluate safety, tolerability, recommended dose (RD) and efficacy of F16-IL2, a recombinant antibody-cytokine fusion protein, in combination with doxorubicin in patients with solid tumors (phase Ib) and metastatic breast cancer (phase II). Six patient cohorts with progressive solid tumors (n D 19) received escalating doses of F16-IL2 [5–25 Million International Units (MIU) of IL2 equivalent dose] in combination with escalating doses of doxorubicin (0–25 mg/m2) on day 1, 8 and 15 every 4 weeks. Subsequently, patients with metastatic breast cancer (n D 10) received the drug combination at the RD. Clinical data and laboratory findings were analyzed for safety, tolerability, and activity. F16-IL2 could be administered up to 25 MIU, in combination with the RD of doxorubicin (25 mg/m2). No human anti-fusion protein antibodies (HAFA) response was detected. Pharmacokinetics of F16-IL2 was dose-dependent over the tested range, with half-lives of ca. 13 and ca. 8 hours for cohorts dosed at lower and higher levels, respectively. Toxicities were controllable and reversible, with no combination treatment-related death. After 8 weeks, 57% and 67% disease control rates were observed for Phase I and II, respectively (decreasing to 43% and 33% after 12 weeks), considering 14 and 9 patients evaluable for efficacy. One patient experienced a long lasting partial response (45 weeks), still on-going at exit of study. F16-IL2 can be safely and repeatedly administered at the RD of 25 MIU in combination with 25 mg/m2 doxorubicin; its safety and activity are currently being investigated in combination with other chemotherapeutics, in order to establish optimal therapy settings.

Original languageEnglish
Pages (from-to)14-21
Number of pages8
JournalCell Adhesion and Migration
Volume9
Issue number1-2
DOIs
Publication statusPublished - 2015

Keywords

  • Antibody
  • Breast neoplasms
  • Clinical trial phase I
  • Immunocytokines
  • Interleukin-2

ASJC Scopus subject areas

  • Cell Biology
  • Cellular and Molecular Neuroscience

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