The FDA has removed its partial clinical hold on the Phase I clinical trials of OncoMed Pharmaceuticals for the cancer-fighting, first-in-class fusion protein ipafricept (FZD8-Fc, OMP-54F28), the company disclosed.

FDA removed the partial hold after OncoMed submitted a clinical safety and efficacy data package for ipafricept along with revised study protocols to the agency’s Division of Oncology Products 1. According to OncoMed, the changes include modified dosing regimens, risk mitigation measures, such as increased monitoring and bone protection strategies, and modified enrollment criteria.

OncoMed added that enrollment and dosing of new patients is expected to resume within the next few weeks, once the institutional review boards (IRBs) of the trial’s sites receive and approve the revised trial protocols.

Responding to reported incidents (13% and 5%, respectively) of mild-to-moderate bone adverse events, OncoMed on June 13 said it was voluntarily halting enrollment in Phase 1 trials for two compounds—ipafricept and another cancer drug targeting the Wnt signaling pathway, vantictumab. The FDA followed up by placing the studies on partial clinical hold, allowing for continued dosing of patients who demonstrated benefit without significant drug-related adverse effects.

“With important input from our clinical investigators and academic bone experts, the OncoMed team has developed modified study parameters intended to avoid potential risks while allowing us to evaluate the therapeutic impact of ipafricept for patients with pancreatic, hepatocellular and ovarian cancers in combination with standard therapy,” Jakob Dupont, M.D., OncoMed's CMO, said in a statement.

Ipafricept is being studied in combination with standard-of-care in three Phase Ib studies—one in pancreatic cancer (Abraxane® +gemcitabine + ipafricept), one in hepatocellular carcinoma (sorafenib + ipafricept), and one in platinum-sensitive ovarian cancer (carboplatin/paclitaxel + ipafricept).

Ipafricept is designed to work by inhibiting the Wnt signaling pathway, selectively binding Wnt ligands that are activators of Wnt signaling. Ipafricept has shown broad anti-cancer stem cell (CSC) and anti-tumor activity in patient-derived xenograft tumor models.

In a single-agent Phase Ia study in patients with advanced solid tumors, ipafricept was well tolerated and demonstrated on-target Wnt pathway modulation, according to results presented by the company in June at the American Society of Clinical Oncology (ASCO) 2014 annual meeting in Chicago.

Developed under a collaboration with Bayer HealthCare, ipafricept is one of five OncoMed compounds now in clinical development phases. The other four include vantictumab as well as demcizumab (anti-DLL4, OMP-21M18), tarextumab (anti-Notch2/3, OMP-59R5), and anti-Notch1 (OMP-52M51)—which depending on the compound target the Notch or Wnt CSC signaling pathways.

“As we advance ipafricept and vantictumab through clinical studies in combination with standard of care, we expect to generate key data from these Phase 1b studies that will support a potential opt-in by our partner Bayer as well as late-stage clinical development,” stated Paul J. Hastings, OncoMed’s Chairman and CEO.

Bayer is one of several big biopharma partners for OncoMed, which has formed additional strategic alliances with Celgene and GlaxoSmithKline.

Celgene and OncoMed agreed in December to jointly develop and commercialize demcizumab and up to five additional anti-CSC product candidates from OncoMed's biologics pipeline, in a deal that could net OncoMed more than $3.3 billion.

The GSK collaboration, stretching back to 2007, could generate more than $1.4 billion for OncoMed, the companies said at the time.

OncoMed has two other antibodies in preclinical development, anti-DLL4/anti-VEGF bispecific (OMP-305B83)—which is part of the Celgene deal—and anti-RSPO3 (OMP-131R10), with IND filings planned for late 2014 or early 2015. OncoMed said it is also pursuing discovery of additional novel anti-CSC and cancer immunotherapy product candidates. 

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