A phase II trial of TLN-4601 in patients with glioblastoma multiforme (GBM) at first progression.

2094 Background: TLN-4601 is a structurally novel farnesylated dibenzodiazepinone that has demonstrated broad in vitro cytotoxicity and in vivo tumor growth inhibition. TLN-4601 exerts its antiproliferative effects by inhibition of the Ras/MAPK signaling pathway and by apoptosis induction through caspase activation. In a phase I trial, TLN-4601 was well tolerated and demonstrated early signs of antitumor activity. As the Ras/MAPK signaling pathway is activated in GBM, together with preclinical animal data showing that TLN-4601 crosses the blood brain barrier and accumulates preferentially in implanted brain tumors, this trial was conducted to determine the activity and safety profile of TLN-4601 in patients with GBM at first progression. Methods: Phase II, multicentre, single arm, open label study of TLN-4601 monotherapy in 40 patients with proven GBM at first progression. All patients received radiotherapy and temozolomide chemotherapy as initial treatment. TLN-4601 was administered at a dose of 480 mg/m...