OncoMed tanks as phase 2 cancer trial flops and Bayer flees

Human tumor cells from the pancreas

OncoMed Pharmaceuticals has begun the week with a double dose of bad news. In back-to-back statements, OncoMed revealed that its Celgene-partnered lead asset had flunked a phase 2 pancreatic cancer trial and Bayer had walked away from two drugs, triggering a 40% drop in its stock price.

News of the failed clinical trial hit first and hardest. The trial enrolled 204 patients with metastatic pancreatic cancer and randomized them to one of three arms. All participants received Abraxane and gemcitabine. One arm received placebo on top of this regimen, while the other two took different courses of OncoMed’s experimental demcizumab. The top-line findings are devoid of reasons to be optimistic about the anti-DLL4 antibody.

Against most measures, the placebo group at least matched the experimental treatment arms. At 5.5 months, the progression-free survival seen in the placebo arm was identical to the result from the pooled treatment cohorts. That is a high point for the treatment arms. The demcizumab arms had a median overall survival of 13.2 months. The placebo group is yet to reach its median overall survival. To finish off the losing streak, the overall response rate in the demcizumab groups came in at 33.1%, eight percentage points lower than that achieved by the placebo regimen.

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The only endpoint against which OncoMed could point to numerical superiority for demcizumab was a measure that combined complete responses, partial responses and stable disease. Close to 75% of subjects in the demcizumab arm met this definition of clinical benefit, compared to 71% of patients in the placebo group.

With the data suggesting demcizumab has come to the end of the road in pancreatic cancer, the drug's future, if it has one, and ability to generate some of the $3 billion in milestone committed to by Celgene will likely lie in other indications. OncoMed is testing demcizumab as a treatment for non-small cell lung cancer.

“Based on the lack of benefit over standard-of-care, which performed remarkably well, we will be discontinuing this trial. We will also discontinue any additional enrollment in our other ongoing demcizumab trials and conduct analyses of the data from those trials as planned,” OncoMed CEO Paul Hastings said in a statement. “OncoMed remains focused on completing and analyzing the results of the two randomized phase 2 clinical trials, PINNACLE and DENALI, that are anticipated in the first half of this year.”

One possible positive for these studies is the pancreatic cancer safety data were “generally” as OncoMed expected. Grade three or greater bleeding affected 8.1% of demcizumab patients, compared to 1.5% of placebo subjects. Investigators also reported heart failure in 3.7% of demcizumab subjects.

With the latest failure coming 15 months after an interim assessment found another candidate was coming up short in a pancreatic cancer trial, the pressure is now on OncoMed to deliver positive news on its earlier-stage assets. In the case of vantictumab or ipafricept, OncoMed will need to do so without the support of Bayer.

Bayer had an option to license the Wnt pathway inhibitors, but has decided against doing so. OncoMed attributed Bayer’s action to “strategic reasons.”