Phase IB Trial of Imo-2055 in Combination with 5-Fu, Cisplatin and Cetuximab in 1st-Line PTS with Recurrent/Metastatic Squamous Cell Carcinoma of the Head and Neck (R/M SCCHN)
التفاصيل البيبلوغرافية
العنوان:
Phase IB Trial of Imo-2055 in Combination with 5-Fu, Cisplatin and Cetuximab in 1st-Line PTS with Recurrent/Metastatic Squamous Cell Carcinoma of the Head and Neck (R/M SCCHN)
Purpose IMO-2055 is a toll-like receptor 9 agonist with potential to enhance the efficacy of antitumor agents through immune stimulation. Methods IMO-2055 was administered to 1st-line pts with R/M SCCHN on days 1, 8 and 15 of each 3-wk cycle in combination with 5-FU, cisplatin and cetuximab. IMO-2055 doses were to be escalated (3 + 3 design) from dose level (DL) 1 (0.16 mg/kg) to DL2 (0.32 mg/kg) and DL3 (0.48 mg/kg) if Results 13 pts (1 F, 12 M) with a median age of 59 (range 42-67) yr received IMO-2055. No DLTs occurred at DL1 (n = 3); at DL2 (n = 4), 2/4 pts experienced DLTs. Although during the DL1 expansion cohort (n = 6), only 1 pt experienced DLTs, the overall safety profile of the combined treatment led to early trial termination. Formally, DL1 (0.16 mg/kg IMO-2055) can be considered as the MTD although it was not confirmed by the SMC, as the trial was prematurely stopped. 12 (92%) pts experienced Gr ≥ 3 treatment-emergent adverse events (TEAEs) with 4 pts having Gr ≥ 3 TEAEs related to IMO-2055. 1 patient died during the trial with serious AEs related to IMO-2055. Most frequently reported Gr ≥ 3 TEAEs were neutropenia (DL1 = 78%; DL2 = 50%), hypokalemia (DL1 = 22%; DL2 = 75%) and hypomagnesemia (DL1 = 11%; DL2 = 75%). PK assessment was very limited; partial responses were observed in 3/13 pts. Conclusion High rates of Gr ≥ 3 neutropenia and electrolyte disturbances were observed. Based on the overall safety data, regimens combining IMO-2055, cetuximab, 5-FU and platinum-containing chemotherapy cannot be recommended for phase ll trials. Disclosure J.P. Machiels: Consultant relationship with Boerhinger Ingelheim Research funding of Sanofie U. Keller: advisory board and speaker T.H. Brummendorf: I am member of advisory boards for Merck and I received honoraria from Merck for educational talks at symposia. T. Goddemeier: Employee of Merck KGaA U. Forssman: Employee of Merck Serono S.A. All other authors have declared no conflicts of interest.