Threshold Pharmaceuticals' TH-302 drug has produced promising clinical trial results in the phase I study performed at MD Anderson's Cancer Center in Houston, US, for treating patients with advanced leukemias.
The study enrolled 32 patients, with either acute myelogenous leukemia (AML) or acute lymphoblastic leukemia (ALL), who were administered with drug dosages ranging from 120mg/m2 to 550mg/m2.
The aim of the research is to determine the maximum tolerated dose (MTD), dose limiting toxicity (DLT), safety, tolerability, clinical activity and pharmacokinetics of TH-302 in patients with advanced leukemia.
In the study, all doses of TH-302 were administered as a 30-60 minute intravenous infusion daily for five days every 21 days, and found that patients established a maximum tolerated daily dose at 460 mg/m2.
Marina Konopleva, MD Anderson Cancer Center Department of Leukemia associate professor, said the findings from the study reported that TH-302 can reduce blasts in patients with refractory advanced leukemias.
''Ongoing preclinical investigations have demonstrated that TH-302 is active as a monotherapy and demonstrate synergistic activity in combination with multiple chemotherapies. We are excited to continue further clinical investigations," Konopleva said.
The efficacy results determined by stabilisation or reduction of bone marrow and peripheral blast counts have demonstrated TH-302 activity in multiple subjects with relapsed/refractory AML and ALL.
Preclinical data reported that TH-302 targets hypoxic regions of both solid tumours and hematologic malignancies, and showed marked expansion of the hypoxic bone marrow areas in diseased mice with ALL.
The preclinical study also showed that TH-302 displayed potent anti-leukemia activity and hypoxia-dependent cytotoxicity against primary ALL and AML models.
The company is also conducting a controlled phase II trial of TH-302 in combination with gemcitabine versus gemcitabine alone in patients with advanced pancreatic cancer and a phase II study assessing TH-302 along with doxorubicin versus doxorubicin alone in soft tissue sarcoma.