This is part of the larger phase I xaluritamig study programme and in this part of the study xaluritamig was combined with abiraterone in patients who are naïve to chemotherapy.

Could you outline the methodology?

It’s a phase I study, so all patients were enrolled. The set dose level was 1.5, which is the maximum dose that has been given in a phase I study with xaluritamig. The dosing of xaluritamig is a little tricky, you need to increase the dose so you start at 0.1 on the first week, 0.3 up to 1.0 and then finally 1.5. This was shown to be a tolerable dose in combination with abiraterone.

What did you find?

The drug was very active – over 50% of patients saw a 90% reduction in PSA and over two thirds, or nearly two thirds, of patients saw a reduction in PSA of 50%.

What impact could these findings have and what’s next?

The impact of the finding is obviously to show excellent activity. It’s going to move into a phase III study. The phase III study is already open, actually, where abiraterone alone is being compared with abiraterone plus xaluritamig in chemo-naïve patients who have failed on a previous androgen receptor signalling inhibitor. The biggest challenge with the study has been the toxicity and trying manage what we call musculoskeletal toxicity. So many men get pain in their legs, pain in their arms, post-dose and so the challenge for us now is going to be how do we better manage this toxicity while maintaining that excellent response.

How do these findings fit into the wider picture of novel therapies in the evolving mCRPC treatment landscape?

I think It fits in. We’re seeing a trend now of much more targeted therapies. So it squarely places xaluritamig alongside drugs like lutetium and alongside other antibody-drug conjugates where we have a target and then the payload in this case is an immune payload but we’re able to use a target and then deliver a payload to a specific target in prostate cancer.