The U.S. Food and Drug Administration (FDA) has granted fast track designation to navicixizumab (OMP-305B83) as a potential therapy for heavily pretreated ovarian cancer, Mereo BioPharma, the therapy’s developer, announced.
Fast track designation is given to investigational compounds that show considerable potential in treating serious conditions for which available treatments still fall short. This designation is meant to expedite clinical development, review process, and entry into the market (if it shows positive results in clinical trials).
“We are pleased that the FDA continues to recognize the potential of navicixizumab to become a viable new treatment option for patients with platinum-resistant ovarian cancer who failed multiple other therapies,” Jill Henrich, senior vice president of regulatory affairs at Mereo BioPharma, said in a press release.
Navicixizumab is a bispecific antibody that targets both Delta-like ligand 4 (DLL4) — involved in the development of cancer stem cells and formation of new blood vessels, critical for tumor growth — and vascular endothelial growth factor (VEGF) — essential for the formation of new blood vessels.
The designation, which is for patients who received more than two prior therapies and/or prior bevacizumab, a therapeutic antibody against VEGF, was based on positive data from a Phase 1a study (NCT02298387) and an ongoing Phase 1b study (NCT03030287) evaluating navicixizumab in people with advanced heavily pretreated ovarian cancer.
In the open-label Phase 1a dose escalation and expansion study, 66 people with various types of refractory solid tumors received escalating doses of navicixizumab once every three weeks. These included 12 women with previously treated ovarian cancer.
Navicixizumab alone reduced tumor size in 19 patients (29%). Among ovarian cancer patients, three (25%) achieved partial responses (at least a 30% decrease in tumor size) and four (33%) achieved stable disease.
Navicixizumab exhibited a toxicity profile consistent with VEGF and investigational DLL4 suppressors, and all adverse events (side effects) were manageable or potentially preventable.
These findings suggested that navicixizumab was a safe and effective therapeutic option for people with several types of tumors, but most promising in ovarian cancer patients.
This led to the development of the ongoing open-label, Phase 1b study evaluating the safety, effectiveness, and pharmacokinetics (how the treatment behaves inside the body) of navicixizumab in combination with Taxol (paclitaxel) in people with platinum-resistant ovarian, fallopian, or primary peritoneal cancer, who received three or more prior therapies and/or bevacizumab.
The study’s primary goal is to determine the occurrence of dose-limiting toxicities. Secondary goals include the assessment of adverse events, treatment response rate, and progression-free survival (PFS) — the time a patient lives without signs of disease progression.
In the dose escalation part, patients received navicixizumab at a dose of 3 or 4 mg/kg on days 1 and 15, and 80 mg/m2 of Taxol on days 1, 8 and 15 of every 28-day cycle. On the expansion study, participants were given the lower dose of navicixizumab (3 mg/kg), as higher doses induced more pronounced chronic toxicity, without increasing effectiveness.
At the last interim analysis, conducted at the end of the first quarter of 2019, the trial had recruited 44 patients (of 60 estimated patients), 41% of whom responded to treatment. Patients’ median PFS was 7.3 months.
Also, a greater proportion of patients (68%) who were not treated previously with bavacizumab responded to combination treatment, compared to patients pretreated with Avastin (30%).
The most common adverse events related to treatment were high blood pressure (68%), fatigue (46%), headache (25%), reduction in neutrophils, a type of white blood cell (21%), diarrhea (18%), pulmonary hypertension (14%), shortness of breath (14%) and swelling of legs or hands (14%).
Henrich added that this designation followed the company’s meeting with the FDA earlier this year, where the FDA “agreed in principle on an outline for a Phase 2 clinical trial that could potentially support accelerated approval of navicixizumab in patients with ovarian cancer who have become resistant to prior therapies.”
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