J clin oncol: Results of clinical trials of DARPin drug MP0250 for the first time using solid tumors

DARPin molecules are a class of small molecules, highly specific binding proteins that can be assembled in a multisexual form and are often used to develop anti-tumor drugs that target multiple signaling path paths.
STRUCTURE MP0250 is a DARPin candidate drug that specificly inhibits endotrine growth factors (VEGF) and hepatocellular growth factors (HGF) to damage the tumor micro-environment.
trial (Phase I) is the first human study of MP0250 to assess the safety, toerability and pharmacodynamics of MP0250 for advanced solid tumors.
In the dose incremental queue, 24 patients received MP0250 treatment at 5 dose levels (0.5-12 mg/kg), 3 hours of intravenous fluids, 2 weeks, and 21 patients received MP0250 treatment (dose confirmation queue) using 1 hour of infusion after the maximum dose (MTD) was clear.
the metabolism of MP0250 in the dose incremental queue, patients treated at a dose of 12 mg/kg developed dose-limiting toxicity.
, the maximum to-dosage of MP0250 is set at 8 mg/kg for 2 weeks or 12 mg/kg for 3 weeks.
most common adverse reactions (AE) were hypertension (69%), proteinuria (51%), diarrhea (36%) and nausea (36%);
most adverse reactions are consistent with VEGF and HGF path suppression.
all patients were exposed to doses throughout the dosing period.
half-life is about 2 weeks.
single-drug anti-tumor activity was observed: 1 case of unrecoalded partial remission, 23 weeks after the progress of the disease, 24 cases of stable condition, stable condition for up to 72 weeks, the medium continuous stabilization time of 18 weeks.
addition, MP0250 is a first-line DARPin candidate drug, good resistance, pharmacogenetics suitable, can further evaluate its effects in combined use with other cancer drugs.
。