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FDA Lifts Hold on Phase I Vantictumab Trials Based on OncoMed Adverse Events Management Plan

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Originally published Sept. 2.

NEW YORK (GenomeWeb) – OncoMed Pharmaceuticals announced this week that the US Food and Drug Administration has lifted its partial clinical hold that was keeping the firm from enrolling patients in Phase I studies of the WNT pathway inhibitor vantictumab.

The FDA lifted the hold after reviewing OncoMed's plans to manage bone-related adverse events observed in these early stage studies. The company told PGx Reporter that it is currently not providing details of its altered clinical trial plan.

Currently, OncoMed is investigating vantictumab in three Phase Ib studies, in advanced non-small cell lung, HER2-negative breast, and pancreatic cancers. The company said that researchers will begin enrolling and dosing patients in these trials in coming weeks after institutional review boards review and approve revised study protocols.

The company launched the study in September 2013 looking at vantictumab in combination with paclitaxel in advanced or metastatic HER2-negative breast cancer patients – currently the only study of the drug in a molecularly defined patient subset. According to the clinicaltrials.gov entry for the trial, which hasn't been updated in some months, the trial is slated to enroll approximately 30 patients.

OncoMed has previously said it is exploring a personalized medicine strategy for vantictumab in breast cancer. However, the company isn't yet ready to publicly discuss the details of this effort yet. The company has indicated plans to also use a test to gauge the predictive biomarker of interest in study participants.

In July of this year, OncoMed voluntarily placed a partial hold on the Phase I trial involving vantictumab after seeing mild-to-moderate bone-related adverse events in trial participants. Then, OncoMed submitted to the FDA revised dosing regimens for the drug, risk management plans, among them closer patient monitoring and strategies to limit bone-related events, and altered the enrollment criteria. After reviewing this information, the FDA has now removed the hold on the study.

At a conference in October last year, researchers presented pharmacodynamic biomarker data from the Phase Ia dose escalation trial involving patients with solid tumors. The analysis showed that vantictumab increased the bone degradation marker beta CTX and decreased bone formation markers P1NP and osteocalcin. "Increases of beta CTX were also observed at lowest dose levels [of vantictumab], and decreases of bone formation markers osteocalcin and P1NP only occurred at higher dose levels," the study investigators concluded in a poster. The four vantictumab dosing schedules in this study were 0.5 mg/kg weekly, 0.5 mg/kg every other week, 1 mg/kg weekly, and 1 mg/kg every three weeks.

OncoMed is focused on developing anti-cancer agents that interrogate biological pathways that help cancer stem cells survive and thereby drive tumor growth. The Wnt pathway is one such mechanism. Vantictumab blocks Wnt signaling by binding to so-called Frizzled receptors. In patient-derived xenograft models, vantictumab has reduced cancer stem cell frequency in different tumor types.

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