On September 24, 2018 OncoMed Pharmaceuticals, Inc. (NASDAQ:OMED), a clinical-stage biopharmaceutical company focused on discovering and developing novel anti-cancer therapeutics, reported that the results of its Phase 1a study with single-agent navicixizumab in patients with refractory solid tumors were published in Investigational New Drugs (Press release, OncoMed, SEP 24, 2018, View Source [SID1234529672]). The results showed that 19 of the 66 patients with various types of refractory solid tumors had tumor shrinkage following treatment with navicixizumab. Notably, 3 of the 12 (25%) ovarian cancer patients treated in the trial achieved a partial response with single-agent navicixizumab therapy. Navicixizumab is a bispecific antibody that was designed to enhance the anti-tumor effect observed with inhibition of DLL4 or VEGF alone.
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"These study results demonstrate that navicixizumab has single-agent anti-tumor activity in several tumor types and is particularly active in heavily pretreated ovarian cancer, a cancer with limited treatment options," said John Lewicki, Ph.D., President and Chief Executive Officer of OncoMed. "We look forward to presenting interim data from our Phase 1b study, which is evaluating navicixizumab in combination with paclitaxel in patients with heavily pretreated platinum-resistant ovarian cancer at the upcoming European Society of Medical Oncology (ESMO) (Free ESMO Whitepaper) meeting."
This Phase 1a multicenter, open-label, dose-escalation trial enrolled sixty-six patients with previously treated solid tumors. The primary endpoint was to determine the maximum tolerated dose. Secondary endpoints included safety, pharmacokinetics, immunogenicity and antitumor activity.
The most commonly enrolled tumor types were ovarian (12), colorectal (11) and cancers of the breast, pancreas, uterus and endometrium (four patients of each). Four patients (three ovarian cancer and one uterine carcinosarcoma) had a partial response, and 17 patients had stable disease. There were 19 patients that had a reduction in the size of their target lesions, including seven patients with ovarian cancer. Six of these seven ovarian cancer patients had prior bevacizumab. Four patients remained on study for >300 days and two of these patients were on study for >500 days. The most common drug related adverse events of any grade were hypertension (58%), headache (29%), fatigue (26%), and pulmonary hypertension (18%). Infusion reactions associated with anti-drug antibodies impacting drug exposure occurred in 11% of patients. The maximum tolerated dose for navicixizumab was not determined based on protocol-defined criteria, but doses of 3-4 mg/kg once every 2 weeks were chosen for the subsequent Phase 1b studies.
A Phase 1b multicenter, open-label, dose-escalation and expansion trial of navicixizumab in combination with paclitaxel in patients with platinum-resistant ovarian cancer who have previously received bevacizumab and/or have failed at least two prior therapies is ongoing. Interim study results will be presented in a poster presentation on October 20, 2018 at the European Society of Medical Oncology (ESMO) (Free ESMO Whitepaper) meeting to be held in Munich, Germany.
About Navicixizumab
OncoMed’s anti-DLL4/VEGF bispecific antibody, navicixizumab, is designed to inhibit the function of both DLL4 and VEGF and thereby induce potent anti-tumor responses while mitigating certain angiogenic-related toxicities. Navicixizumab was developed utilizing OncoMed’s BiMAb bispecific platform technology, which enables the design of bispecific antibodies comparable to traditional monoclonal antibodies but possessing dual target-binding specificity. In preclinical studies, navicixizumab demonstrated robust in vivo anti-tumor efficacy across a range of solid tumor xenografts, including colon, ovarian, lung and pancreatic cancers, among others. Further, in preclinical studies dual inhibition of DLL4 and VEGF appeared to exhibit synergistic anti-tumor activity at doses where blockade of either target alone elicited sub-optimal activity.