Date: 2017-01-20
Type of information: Presentation of results at a congress
phase: 2
Announcement: presentation of results at the ASCO Gastrointestinal Cancers Symposium
Company: Mateon Therapeutics (USA - CA), previously known as Oxigene (USA - CA)
Product: CA4P (fosbretabulin tromethamine)
Action
mechanism: vascular disrupting agent/mitotic inhibitor/tubulin binder. CA4P (combretastatin-A4 phosphate or fosbretabulin) is an investigational vascular disrupting agent (VDA) product candidate, Upon administration, fosbretabulin is dephosphorylated to its active metabolite, combretastatin A4, which targets and binds to tubulin dimers and prevents microtubule polymerization, thereby resulting in mitotic arrest and apoptosis in endothelial cells. It also disrupts the engagement of the endothelial cell–specific junctional molecule vascular endothelial-cadherin (VE-cadherin) and so the activity of the VE-cadherin/?-catenin/Akt signaling pathway, which may result in the inhibition of endothelial cell migration and capillary tube formation. As a result of fosbretabulin's dual mechanism of action, the tumor vasculature collapses, resulting in reduced tumor blood flow and ischemic necrosis of tumor tissue.
Disease: unresectable, recurrent or metastatic pancreatic or gastrointestinal neuroendocrine tumors
Therapeutic area: Cancer - Oncology
Country:
Trial
details: Study OX4218 was a multi-center, open label, phase 2 clinical trial to investigate the safety and activity of combretastatin A4-phosphate (CA4P) in the treatment of well-differentiated, low-to-intermediate-grade unresectable, recurrent or metastatic pancreatic or gastrointestinal neuroendocrine tumors/carcinoid (PNETs or GI-NETs) with elevated biomarkers. Following patients' completion of Study OX4218, patients were eligible to enroll in Study OX4219, a long term extension study, if they achieved a biomarker or symptom response. In OX4218 patients were treated with CA4P 60 mg/m2 on Days 1, 8, and 15 of a 21-day cycle for 3 cycles, and in OX4219 patients received CA4P maintenance on Day 1 of a 21-day cycle until disease progression or up to one year.
Latest
news: * On January 20, 2017, Mateon Therapeutics announced the presentation of final data from Study OX4218 in patients with neuroendocrine tumors (NETs) at a poster session at the ASCO Gastrointestinal Cancers Symposium being held in San Francisco . A total of 18 patients were enrolled in study OX4218. One patient (6%) experienced significant symptomatic improvement as measured by ECOG Status and had a partial response per investigator-assessed RECIST and an additional 7 patients (39%) had stable disease. In addition, a majority of patients (53%) experienced an improvement in patient-reported quality of life. A statistically significant mean change in biomarkers from baseline, the primary endpoint of the study, was not achieved in OX4218 due to the small sample size along with a high intra- and inter-patient variability observed in the biomarkers. A total of 7 patients were enrolled in OX4219, of which 5 patients (71%) had stable disease, including one that continued for 14 months. The partial response and stable disease analyses, as well as other measures from the trial, suggest that CA4P monotherapy has activity in this indication. "The results of OX4218 and OX4219 confirm that CA4P monotherapy has efficacy in the indications studied, as we have seen with the investigational drug in a number of other monotherapy trials," said William D. Schwieterman , M.D., President and Chief Executive Officer of Mateon. "However, we believe that the efficacy of CA4P only becomes compelling when it is used in combination with an anti-angiogenic agent, due to the complementary mechanisms of action for the two agents. Based on the evidence of efficacy observed in this trial, plus an understanding of the benefits of combination therapy, a lead investigator in this trial is sponsoring a 20 patient study in NETs using CA4P in combination with everolimus (AFINITOR®, marketed by Novartis), an anti-angiogenic agent which is already approved and commonly used in this indication."
Overall CA4P monotherapy was well tolerated. Treatment related adverse events were reported in 77% of subjects. The most common Grade 3-5 AEs ( > 10%) included: anemia, abdominal pain, fatigue, hypertension, and ALT and AST increases. One Grade 5 adverse event, carcinoid syndrome, was reported and attributed to the underlying disease.
