OXiGENE is currently investigating the use of ZYBRESTAT in a Phase 2 study of patients with non-small cell lung cancer, and 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 recently 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.

ZYBRESTAT in Non-small Cell Lung Cancer (NSCLC)

OXIGENE is evaluating the use 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 was 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).

ZYBRESTAT in Ovarian Cancer

ZYBRESTAT is also currently being evaluated in a randomized Phase 2 trial of ZYBRESTAT in combination with bevacizumab in patients with relapsed ovarian cancer. The study, which is being conducted by investigators from the Gynecologic Oncology Group (GOG), is expected to enroll approximately 105 patients with a primary endpoint of progression-free survival. OXiGENE expects results of the study to become available in early 2013.

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.

Investigators from the GOG approached OXiGENE after seeing positive data from a Phase 2 study of ZYBRESTAT and chemotherapy in patients with platinum-resistant ovarian cancer. The current study is designed to investigate an alternative approach to treating relapsed ovarian cancer by exclusively targeting tumor vasculature without the use of chemotherapy.

Earlier Positive Phase 2 Data in Ovarian Cancer

OXiGENE reported positive final data from an investigator-sponsored Phase 2 study of ZYBRESTAT in patients with platinum-resistant ovarian cancer at the 2009 Annual Meeting of the American Society of Clinical Oncology (ASCO). Platinum resistance was defined as disease relapse within 6 months of completing treatment with platinum-based therapy, and the patients enrolled in the study would therefore not have been expected to respond to further treatment with platinum-based therapy. Of 44 patients enrolled in the study, 11 (25%) had confirmed partial responses as determined by the Gynecologic Cancer InterGroup (GCIG) response criteria, i.e., response by tumor imaging (RECIST) and/or ovarian cancer biomarker (CA-125) criteria. An additional 4 patients had unconfirmed partial responses, and stable disease responses were reported in an additional 16 patients. The combination regimen of ZYBRESTAT and carboplatin plus paclitaxel chemotherapy was observed to be well-tolerated with approximately half of the patients completing all 6 cycles of therapy. The Phase 2 trial was a single-arm, Simon two-stage design study evaluating the safety and efficacy of the combination of ZYBRESTAT and chemotherapy (carboplatin and paclitaxel).