OXiGENE reports positive final data from Phase 1 study of OXi4503 in patients with solid tumors

OXiGENE, Inc. (Nasdaq:OXGN), a clinical-stage, biopharmaceutical company developing novel therapeutics to treat cancer and eye diseases, announced today that in collaboration with OXiGENE, Professor Gordon Rustin and colleagues from the Mount Vernon Cancer Research Centre, UK and other institutions in the United Kingdom, reported positive final data from an investigator-sponsored Phase 1 study of OXi4503 in patients with solid tumors. Data from a dose escalation study of 45 patients with advanced solid tumors who had declined or were refractory to standard treatment were presented at the 2010 Annual Meeting of the American Society of Clinical Oncology (ASCO). Partial responses were observed in two patients with epithelial ovarian cancer and stable disease was observed in 9 patients. OXi4503 was also shown to be well-tolerated.

The data were presented in a poster titled, "Phase 1 Pharmacokinetic and Pharmacodynamic Evaluation of the Vascular Disrupting Agent OXi4503 in Patients with Advanced Solid Tumors," by  Dr. Martin Zweifel of the Mount Vernon Cancer Centre, UK.

"The data from this study provide excellent insight into the tolerability and potential optimal dosing schedule for OXi4503, with intriguing and encouraging signs of activity," commented Peter Langecker, M.D., Ph.D., OXiGENE CEO. "Of particular clinical interest are the two patients with epithelial ovarian cancer who achieved partial responses and the 9 patients with stable disease. We believe that OXi4503 is a highly promising, second-generation, dual action vascular disrupting agent with potential both as a single agent and in combination with other treatment modalities. The encouraging results from this Phase 1 study suggest that a Phase 2 study of OXi4503 in patients with solid tumors would be an exciting next step."

In this study, OXi4503 was given intravenously in escalating doses ranging from 0.06 to 15.4 mg/m2. Dose levels of 8.5, 11.0, 12.5, and 14 mg/m2 were repeated following the introduction of amlodopine as prophylaxis to prevent hypertension. 

Key data points from the Phase 1 study of OXi4503 are as follows. 

• OXi4503 was observed to be well-tolerated; common adverse events included tumor pain, nausea, hypertension, fatigue and myelosuppression.
• Drug-related dose-limiting toxicities of grade 3 hypertension and visual disturbances were seen in two patients at 15.4 mg/m2 before the introduction of amlodopine as prophylaxis.
• One dose-limiting toxicity (grade 3 troponin level elevation) at 11 mg/m2 was seen thereafter.
• 67% of evaluable patients showed DCE-MRI changes consistent with VDA activity.
• Best observed responses include 2 RECIST partial responses at 11 mg/m2 and 14 mg/m2 in patients with epithelial ovarian cancer.
• The investigators recommend a phase 2 dose between 11 and 14 mg/m2.

The company also announced that two posters describing trials investigating OXiGENE drug candidates were presented as part of the new "Trials in Progress" session of the ASCO annual meeting.  

• #TPS164: A multicenter, open-label phase Ib/II study to assess the safety and clinical activity of intravenous combretastatin A1 diphosphate (OXi4503) as monotherapy in subjects with primary or secondary hepatic tumor burden. Poster presentation by Paul N. Mainwaring, M.D.
   
• #TPS147: A pilot study of fosbretabulin with bevacizumab in recurrent high-grade gliomas. Poster presentation by Ramin Altaha, M.D.