1044P - 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 th...

Date 01 October 2012
Event ESMO Congress 2012
Session Poster presentation III
Topics Drug Development
Head and Neck Cancers
Presenter Jean-Pascal Machiels
Authors J. Machiels1, M.C. Kaminsky2, U. Keller3, T.H. Brümmendorf4, T. Goddemeier5, U. Forssman6, J.P. Delord7
  • 1Medical Oncology, Cliniques Universitaires St. Luc, 01200 - Brussels/BE
  • 2Département D'oncologie Médicale, Centre Alexis Vautrin, 54511 - Nancy/FR
  • 3Iii. Medizinische Klinik, TU München, Munchen/DE
  • 4Hämatologie Und Onkologie, Universitätsklinikum Aachen, 52074 - Aachen/DE
  • 5Global Clinical Operations / Global Biostatistics, Merck KGaA, 64293 - Darmstadt/DE
  • 6Global Clinical Development Unit Oncology, Merck Serono S.A, 1202 - Geneva/CH
  • 7Clinical Resarch Unit, Centre Claudius-Regaud, FR-31052 - Toulouse/FR

Abstract

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 <1/3 pts or <2/6 pts in the previous DL had dose-limiting toxicities (DLTs). DLTs were defined as any Gr3/4 treatment-related toxicity in cycle 1 confirmed by the safety monitoring committee (SMC). Expansion cohorts were planned at DL1 and at the maximum tolerated dose (MTD) level. A maximum of 6 cycles of combined treatment was planned; pts were to continue cetuximab and IMO-2055 until disease progression. Primary objective was to determine the MTD; other objectives included evaluation of safety profile, PK and antitumor effects.

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. Brümmendorf: 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.