AMG 509 (Xaluritamig) in Patients With mCRPC

Dr. Sartor: Also presented at ESMO 2023 is an interesting first-in-human study of a novel compound called AMG 509. Let me explain what this is because you may not be familiar with it.

This is a bispecific antibody. One arm of the antibody binds to STEAP1, which is an antigen on the surface of prostate cancer cells. The other arm of the antibody binds to CD3, a T-cell engager, and this bispecific engagement is going to create T-cell activation in the microenvironment of prostate cancer cells expressing the STEAP1 antigen.

A lot of activity with higher dose levels

Now, as I mentioned, this is a first-in-human study, and this is the first presentation of these data. Well, as you can imagine, a lot of the patients had very low doses in phase I, which are not particularly relevant for determining activity. When they started to get up to the higher dose levels, however, there was a lot of activity seen in patients who were refractory to typical therapies. And I'll simply say, once you got up to the higher dose levels, looking at PSA 50% decline or better, 54% of the patients met that metric. Partial responses by RECIST criteria were present for 38.9%. PSA 90% declines were found in 34.8%.

A variety of toxicities

Now, there were a variety of toxicities, and you can get cytokine-release syndrome with this, including fever, including fatigue, maybe low blood pressure. These things are being worked through. They're still working on the optimal way to dose and the optimal way to give this particular therapy. So, the AMG 509 is not ready for prime time. It is not ready to go into phase II or phase III. There's additional exploration that's going to be required.

AMG 509 is promising

But I thought it was interesting, because STEAP1 is a new target, and bispecific antibodies are still relatively novel in prostate cancer. And this particular STEAP1, CD3 bispecific had activity, without a doubt had activity in heavily pretreated patients. So, I look forward for more to come on this particular molecule.