Conatumumab or AMG 479 as treatment for pancreatic cancer

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Published: 25 Jun 2010
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Prof Hedy Kindler - University of Chicago, USA
Prof Hedy Kindler outlines the results of a randomised phase II trial investigating the use of conatumumab or AMG 479 as a treatment for pancreatic cancer. Both monoclonal antibodies had positive effects and led to an increased length of progression free survival, however this increase was greater with AMG479. The side effects were minimal and the team will shortly be starting a phase III trial.

This interview is supported by an unrestricted educational grant from AMGEN.

ASCO 2010 Annual Meeting, 4—8 June 2010, Chicago

Professor Hedy Kindler (University of Chicago, USA)

Conatumumab or AMG 479 as treatment for pancreatic cancer

What did you present at ASCO with regarding new treatments for pancreatic cancer?

This was a randomised Phase II study of gemcitabine with either a placebo, conatumumab, or AMG 479. Conatumumab is a monoclonal antibody to DR5 which affects the trail pathway affecting apoptosis, and AMG 479 is an IGF-1R monoclonal antibody.

So, this was a double-blind placebo-controlled randomised Phase II study that had a primary end point of six month progression-free survival, and the data showed the value of a randomised Phase II trial in this disease because we saw that the placebo-controlled arm had a progression-free survival of 2.1 months, and a median overall survival of 5.9 months.

In contrast, the two antibody arms – the experimental arms – both had superior progression-free and overall survival. There was progression-free survival on the conatumumab arm of four months, and on the AMG 479 arm of 5.9 months, and overall survival of 8.7 months on the conatumumab arm, with actually a hazard ratio of 0.67, suggesting that we should be moving forward with AMG 479 in this disease.

How many patients did the trial involve?

125 patients – so it was a design for 40 per arm.

Did you encounter any issues with increased toxicities?

Not significantly. For 479, that arm was unblinded, because initially, we anticipated an increase in hyperglycaemia and thrombocytopenia, and felt that we needed to monitor for it. There was no increase in thrombocytopenia, and it was a grade of 18% of grade 3 or 4 hyperglycaemia, which, in a pancreatic cancer patient study is not that big a deal. These patients are mostly diabetic anyway.

Are there plans for a Phase III trial?

So, a Phase III trial is right now in development, yes – 479. It was a difficult decision whether to go forward with both conatumumab and 479, or just 479, but we all felt that the data was stronger with the 479.

What impact is this research likely to have on patients?

I’d say that pancreatic cancer is a devastating disease. It’s a very difficult disease to treat. It’s a difficult disease for us to move forward with in new therapies. The data that we showed is not a home run, but it certainly shows a distinct improvement, and it offers some hope that we may be able to alter the course of this disease.