A second interim analysis of a trial designed to evaluate the addition of CA4P to standard therapy for patients with platinum-resistant ovarian cancer showed a small PFS benefit for the combination.
However, the difference did not reach statistical significance.
The phase 2/phase 3 FOCUS trial is investigating the addition of fosbretabulin (CA4P, Mateon Therapeutics) — a potent tubulin-binding vascular disrupting agent — or placebo to bevacizumab (Avastin; Genentech, Roche) and physician’s choice of chemotherapy.
PFS serves as the primary endpoint. Secondary endpoints include objective response rate and safety.
The second interim analysis was based on results from the first 40 patients with platinum-resistant ovarian cancer treated with fosbretabulin (n = 19) or placebo (n = 21) who have been treated for at least 2 months or discontinued the trial.
Researchers reported a small PFS benefit with the fosbretabulin regimen (median, 6.64 months vs. 4.96 months; HR = 0.68); however, the difference did not reach statistical significance.
Six patients (31.6%) who received fosbretabulin and 10 patients (47.6%) who received placebo progressed or died while on study.
Four patients (25%) treated with fosbretabulin and six patients (40%) in the control group achieved partial responses. Nine patients (56.3%) treated with fosbretabulin and 11 patients (57.9%) in the control group achieved stable disease.
Fosbretabulin has demonstrated a favorable safety profile. More patients who received fosbretabulin than placebo experienced transient increases in blood pressure (57.9% vs. 9.5%), but rates of grade 3 hypertension were similar between groups (21.1% vs. 23.8%). One case of grade 4 hypertensive crisis occurred in the fosbretabulin group.
Adverse events that occurred more frequently in the fosbretabulin group included nausea, fatigue, cough and hypertension. Most were mild to moderate.
Incidence of neutropenia, anemia and thrombocytopenia was low, with similar rates between treatment groups.
“We are encouraged that early data on the primary endpoint of the study continue to favor CA4P and that our investigational drug remains well tolerated,” William D. Schwieterman, MD, president and CEO of Mateon Therapeutics, said in a company-issued press release.
Ninety-one patients have been enrolled in the phase 2 portion of the trial.
A third interim analysis will be conducted when approximately 75% of enrolled patients have been treated for at least 2 months or have discontinued treatment.
“There is a large unmet medical need in the ovarian cancer market as patients with platinum-resistant ovarian cancer have low survival rates and few treatment options,” Schwieterman said in the release. “We look forward to additional and more mature data from third interim analysis, expected just over 1 month from now. In this upcoming analysis, we will have more data on the current patients, who will have had additional time under treatment, as well as initial efficacy and safety information on approximately 25 additional patients.”