OXiGENE is currently investigating the use of ZYBRESTAT in a Phase 2 study of patients with relapsed ovarian cancer. For more information on these clinical trials, please visit our clinical trials page.
OXIGENE also recently announced encouraging results from a Phase 2 study of patients with anaplastic thyroid cancer (ATC).
ZYBRESTAT in Anaplastic Thyroid Cancer (ATC)
OXIGENE has presented data from the FACT trial, a study of ZYBRESTAT plus chemotherapy in patients with anaplastic thyroid cancer (ATC). In this 80-patient study, the median overall survival (OS) time was 5.2 months for patients who received ZYBRESTAT and chemotherapy compared with 4.0 months for patients receiving chemotherapy alone (Hazard Ratio (95% CI) of 0.72 (0.43, 1.20)), representing a 28% reduction in the risk of death for patients receiving ZYBRESTAT and chemotherapy. For patients treated with ZYBRESTAT and chemotherapy, the likelihood of being alive at six months was 48% compared with 35% for patients treated with the control arm regimen. At one year, the likelihood of being alive was 26% for patients treated with ZYBRESTAT and chemotherapy compared with 9% for patients treated with chemotherapy alone. As in other studies of ZYBRESTAT, the most clinically relevant side effects reported in the study were neutropenia, transient hypertension, clinically asymptomatic QTc prolongation and tumor pain.
OXiGENE does not plan to conduct additional clinical testing of ZYBRESTAT in ATC. The company is exploring a regulatory and commercial strategy that could enable marketing of ZYBRESTAT in Europe for ATC based on existing data. This strategy could take advantage of the EU's Marketing Authorization process for ultra-rare indications. The company believes this strategy would be relatively inexpensive to pursue, as it would likely not require additional clinical testing.
ZYBRESTAT in Non-small Cell Lung Cancer (NSCLC)
OXIGENE has completed evaluation of ZYBRESTAT in the FALCON study, a randomized, controlled study investigating the addition of ZYBRESTAT (fosbretabulin tromethamine, or CA4P) to standard therapy (carboplatin, paclitaxel, and bevacizumab, or C/P/Bev) in patients with Stage IIIb or IV predominantly non-squamous NSCLC.
Interim data from this study were presented at the 2011 Annual Meeting of the American Society for Clinical Oncology (ASCO) in Chicago, Illinois. An updated analysis conducted approximately 11 months after the enrollment of the last patient in June 2010 showed that the combination regimen of ZYBRESTAT plus bevacizumab, carboplatin and paclitaxel (ZYBRESTAT Arm) was observed to be well-tolerated with no significant cumulative toxicities when compared with the control arm of the study. In addition, a pre-specified subgroup analysis showed meaningful improvements in median time to progression for patients with poor performance status (ECOG Performance Status 1). While the median time to progression for the overall patient population was similar in both arms of the study, 8.6 months for the ZYBRESTAT arm compared with 9.0 months on the control arm, an analysis of the patient strata showed that patients with poor performance status who received ZYBRESTAT in addition to bevacizumab and chemotherapy achieved a median time to progression of 9.8 months compared with only 3.8 months for patients in this same subgroup on the control arm of the study with a hazard ratio (95% CI) of 0.51 (0.23, 1.16).
OXiGENE does not plan to pursue additional development of ZYBRESTAT in this indication.
ZYBRESTAT in Ovarian Cancer
ZYBRESTAT is currently being evaluated in a randomized Phase 2 trial of ZYBRESTAT in combination with bevacizumab in patients with relapsed ovarian cancer. The study is being conducted under a Cooperative Research and Development Agreement (CRADA) with the National Cancer Institute (NCI) for ZYBRESTAT and a CRADA with Genentech for the development of bevacizumab. The aim of the trial, sponsored by the NCI's Division of Cancer Treatment and Diagnosis, is to determine if the combination of ZYBRESTAT and bevacizumab will enhance anti-tumor effects and further delay tumor progression when compared to bevacizumab alone.
To be eligible for the study, patients must have measurable or detectable recurrent or persistent epithelial ovarian, fallopian tube or primary peritoneal carcinoma, and must have had one prior platinum-based chemotherapeutic regimen for management of primary disease containing carboplatin, cisplatin or another organoplatinum compound. Patients can be either platinum-sensitive or platinum-resistant but cannot have received more than two prior chemotherapy regimens.
Patients are randomized into two arms: one arm receives bevacizumab 15 mg/kg IV on day 1 and then every three weeks; the second arm receives bevacizumab plus fosbretabulin tromethamine 60 mg/m2 IV on day 1 and then every three weeks. Patients are treated until disease progression or until adverse effects prohibit further therapy. The primary endpoint of the Phase 2 trial is progression-free survival. Secondary endpoints include safety, overall survival and objective responses by treatment arm. OXiGENE anticipates top-line data analysis of the trial by the end of 2013.