Mateon Therapeutics said it will eliminate 60% of its workforce and end the development of its cancer-fighting lead candidate CA4P (combretastatin A4-phosphate, or fosbretabulin) following its failure in a Phase II/III trial.
Mateon has terminated the Phase II/III FOCUS study, which assessed CA4P in combination with Roche-owned Genentech’s Avastin® (bevacizumab) and physician’s choice chemotherapy in patients with platinum-resistant ovarian cancer.
The company acknowledged that CA4P missed its primary endpoint, progression-free survival (PFS), in the trial. While results favored patents treated with CA4P—who showed a 32-day increase in median PFS compared to control-group patients, 202 vs. 170 days—their improvement was not statistically signficant, Mateon concluded following its third scheduled interim analysis of data from the study.
No patients showed complete response, while more patients showed partial response in the control group (17) than in the group treated with CA4P (16). Also, more control patients (17) than CA4P patients (16) showed a stable disease response. CA4P did surpass the control group among patients showing progressive disease, by 5 to 3.
“Due to the lack of a meaningful improvement in PFS, combined with the unfavorable partial response data, the company does not believe that continuation of the study is appropriate,” Mateon stated yesterday.
CA4P is a potent, tubulin-binding vascular disrupting agent (VDA) that, according to Mateon, had previously shown the most robust and consistent evidence of tumor blood flow shutdown among its VDAs in clinical trials.
CA4P was designed to fight cancer by targeting tumor blood vessels, ultimately depriving tumors of oxygen and essential nutrients, leading to the death of interior tumor cells, but sparing some cells on the outer rim of the tumor where cells could derive their nutrients from blood vessels in the proximal normal tissue.
In addition to platinum-resistant ovarian cancer, Mateon had explored CA4P’s potential use in other tumor types, such as neuroendocrine tumors (NETs), glioblastoma multiforme (GBM), hepatocellular carcinoma, and gastric cancer.
FOCUS enrolled 91 patients who were randomized to CA4P or placebo plus the current standard-of-care for platinum-resistant ovarian cancer, consisting of Avastin and chemotherapy.
“We are clearly disappointed that CA4P did not show a clinically meaningful benefit when it was added to the current standard of care in platinum-resistant ovarian cancer,” Mateon president and CEO William D. Schwieterman, M.D., stated. “The outcome is clear, and unfortunately negative.”
As a result, Mateon said, it will carry out near-term cost reduction measures that include the 60% reduction in workforce. The company employed 16 full-time employees as of March 30, according to its Form 10-K annual report for 2016, filed that day.
Remaining members of Mateon’s senior management team will take 50% salary reductions, effective immediately, the company added.
Going forward, Mateon said, it would seek to “obtain value from” its development program for OXi4503 (combretastatin A1-diphosphate, or CA1P) in acute myeloid leukemia (AML). OXi4503 is a dual-mechanism VDA that is being developed for AML as well as for myelodysplastic syndrome (MDS).
On July 31, Mateon trumpeted positive preliminary data from the Phase Ib OX1222 dose-ranging study, assessing OXi4503 in combination with cytarabine in patients with relapsed/refractory AML or myelodysplastic syndrome (MDS). Up to that point, five of 21 study patients in OX1222 had achieved complete remission—with two of four patients showing morphological complete remissions after receiving just one cycle of treatment with 9.76 mg/m2 of OXi4503; both were set to receive a second cycle of treatment.
At the time, Mateon said it was in “continuing pharmaceutical partnering discussions” to secure a partner or additional capital before launching additional clinical studies of OXi4503 in AML.
Mateon also left open the door for additional selloffs, up to and including the company itself. “As always, we are exploring all options for additional fundraising and adding value for our stockholders, which includes continuing to look for buyers for any or all of our assets.”
OX1222 is estimated to enroll 105 patients, with an estimated primary completion date of October, and an estimated study completion date of October 2020.