Service Description

Covance ran an in vivo efficacy study in mouse tumor xenografts and a tox study in Wistar Han Rats with a proprietary Antibody drug conjugate. Covance set up three studies for us. A two arm efficacy study in mouse tumor xenografts where one arm and high target expression and the other arm had low expression. The antibody drug conjugate was treated at three doses two times a week for three weeks with a one week holiday before the animals were terminated. Tumor size was measured each day over the 30 day study and at the end point the tumors were harvested for IHC of target expression and several PD markers were measured by western blot. The rat tox study was an MTD study over two weeks where the ADC was treated up to 30 mg/kg and full body tox monitoring was performed at the end point.

What Went Well

Covance was quite experienced in running these types of tumor efficacy and tox studies in mice and rats respectively. They did a nice job setting up the experiments and consulting us for the final approved plan. The protocols they used were quite similar to our protocols so we had confidence they results would be similar to our in house studies. They ran the experiments in a timely manner and reported data in real time to us. Overall they did a great job running the experiments carefully and the best part of the interaction was their attention to detail and willingness to speak with us directly when there was a question or challenge facing the study.

What Could Be Improved

Although they did a great job on the study they had little experience with antibody drug conjugates and had to troubleshoot some of the technical aspects of the injections. I don't think this is a particular problem because they were able and willing to adapt the protocol to run the experiment properly. Also the tumor harvesting procedure had to be adapted at the last minute and if they would not have been communicative about the project we would have lost the entire 45 day experiment. I view that as a close call and they should be careful to plan well in advance for all steps in a protocol.

Lessons Learned from the Experience

I learned that if you have a particular protocol and experiments you need to perform that you have extensive dialog about the details with the CRO. Even a small mistake could bring down the whole study if one step is not clearly spelled out. This might sound obvious but being overly careful is my lesson learned. We had a close call and we now have implemented an oversight team internally to double check our CRO work.