Gil Roth11.22.13
Threshold Pharmaceuticals has posted early data from the Phase I portion of the investigator-sponsored Phase I/II trial of its investigational hypoxia-targeted drug TH-302 in combination with Avastin (bevacizumab) in patients with recurrent glioblastoma following bevacizumab failure (Study 4003).
No dose-limiting toxicity has been reported to date at doses of TH-302 as high as 670 mg/m2 plus bevacizumab at 10 mg/m2 every two weeks. Preliminary data in 14 patients showed TH-302 in combination with bevacizumab was associated with a median time to progression of 2.8 months. One patient achieved a complete response and two patients achieved partial responses.
Chemotherapy with radiotherapy is standard care for newly diagnosed glioblastoma. Bevacizumab is approved in the U.S. for progressive disease following prior therapy. After disease progression on bevacizumab, patients may start a subsequent bevacizumab-containing regimen. These patients typically progress in 5 to 8 weeks. Three-month progression-free survival is approximately 15%.
A total of 19 patients have been enrolled in the ongoing trial. Of 14 patients evaluable for tumor response, the median time to progression was 86 days. Forty-six percent of patients were alive without disease progression after three months of treatment. Best tumor responses were one patient achieving a complete response, two patients achieving a partial response, and seven patients demonstrating stable disease; four patients experienced progressive disease. The longest disease stabilization is currently ongoing in one patient who achieved a partial response and is currently receiving cycle 26 at 22 months.
No grade 4 adverse events were observed at any dose. Two grade 3 adverse events were observed at 340 mg/m2 and 670 mg/m2 of skin ulceration and thrombocytopenia, respectively. The primary TH-302 related toxicities were mucosal, with rectal mucositis in two of four patients at 480 mg/m2 and four of four patients at 670 mg/m2. Limited oral mucositis was observed. Mucositis was treated conservatively and was not dose limiting.
The Phase I/II trial is a single-center, dose-escalation trial in patients with recurrent glioblastoma whose disease has progressed following initial combined modality treatment with radiotherapy and temozolomide and subsequent treatment with bevacizumab.
No dose-limiting toxicity has been reported to date at doses of TH-302 as high as 670 mg/m2 plus bevacizumab at 10 mg/m2 every two weeks. Preliminary data in 14 patients showed TH-302 in combination with bevacizumab was associated with a median time to progression of 2.8 months. One patient achieved a complete response and two patients achieved partial responses.
Chemotherapy with radiotherapy is standard care for newly diagnosed glioblastoma. Bevacizumab is approved in the U.S. for progressive disease following prior therapy. After disease progression on bevacizumab, patients may start a subsequent bevacizumab-containing regimen. These patients typically progress in 5 to 8 weeks. Three-month progression-free survival is approximately 15%.
A total of 19 patients have been enrolled in the ongoing trial. Of 14 patients evaluable for tumor response, the median time to progression was 86 days. Forty-six percent of patients were alive without disease progression after three months of treatment. Best tumor responses were one patient achieving a complete response, two patients achieving a partial response, and seven patients demonstrating stable disease; four patients experienced progressive disease. The longest disease stabilization is currently ongoing in one patient who achieved a partial response and is currently receiving cycle 26 at 22 months.
No grade 4 adverse events were observed at any dose. Two grade 3 adverse events were observed at 340 mg/m2 and 670 mg/m2 of skin ulceration and thrombocytopenia, respectively. The primary TH-302 related toxicities were mucosal, with rectal mucositis in two of four patients at 480 mg/m2 and four of four patients at 670 mg/m2. Limited oral mucositis was observed. Mucositis was treated conservatively and was not dose limiting.
The Phase I/II trial is a single-center, dose-escalation trial in patients with recurrent glioblastoma whose disease has progressed following initial combined modality treatment with radiotherapy and temozolomide and subsequent treatment with bevacizumab.