Catania, Chiara Maur, Michela Berardi, Rossana Rocca, Andrea Maria Di Giacomo, Anna Spitaleri, Gianluca Masini, Cristina Pierantoni, Chiara González-Iglesias, Reinerio Zigon, Giulia Tasciotti, Annaelisa Giovannoni, Leonardo Lovato, Valeria Elia, Giuliano D Menssen, Hans Neri, Dario Cascinu, Stefano Franco Conte, Pier de Braud, Filippo 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 <div><p>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 = 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/m<sup>2</sup>) on day 1, 8 and 15 every 4 weeks. Subsequently, patients with metastatic breast cancer (n = 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/m<sup>2</sup>). 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/m<sup>2</sup> doxorubicin; its safety and activity are currently being investigated in combination with other chemotherapeutics, in order to establish optimal therapy settings.</p></div> metastatic breast cancer;rd;25 MIU;IL 2 equivalent dose;combination;mg;9 patients evaluable;HAFA;safety;tumor;phase;doxorubicin;ii 2015-10-08
    https://tandf.figshare.com/articles/dataset/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/1285024
10.6084/m9.figshare.1285024.v5