Anti-TNF a magic bullet in cancer immunotherapy?

摘要

Scheme of the TICIMEL phase-1b clinical trial in 30 advanced melanoma patients. , TICIMEL is split in 2 consecutive parts with the first part being conducted in 2 parallel cohorts (Cohort 1 and Cohort 2 with alternative patient allocation) to evaluate the safety profile of combining Nivolumab+Ipilimumab with TNF-Inhibitors (Certolizumab in cohort 1 and Infliximab in Cohort 2). Three patients are included at the unique dose. If there is no DLT or only one DLT, three other patients will be included. If no more than one patient among 6 presents a DLT, the combination (ICB + anti-TNF) will be considered as safe and allow to pursue the second part of the trial. The combination therapy selected for the second part of the study (cohort expansion study) will depend on safety, activity, and pharmacodynamics data from the first part of TICIMEL. , Nivolumab and Ipilimumab are administered intravenously (IV) (infusion duration of 60 min for Nivolumab and 90 min for Ipilimumab); Certolizumab is administered subcutaneously (SC). Infliximab is administered IV (infusion duration of 120 min). All treatments are given on the same day as indicated in the induction phase. During the maintenance phase, Nivolumab and Certolizumab or Infliximab are/will be co-administered as indicated. Patients undergoing disease control (CR, PR or stable disease) beyond one-year treatment will have the possibility to be maintained on Nivolumab (3 mg/kg, Q2W). The end of Dose Limiting Toxicity (DLT) period evaluation is at day 84