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Tian Zhang: Hi, and welcome to this episode of UroToday. I'm Tian Zhang, GU medical oncologist and associate director of clinical research at UT Southwestern Medical Center in Dallas, Texas. I'm joined today by a colleague from all the way in Australia, Dr. Andrew Parsonson. He's a consultant medical oncologist at Macquarie University Hospital in Sydney in Australia, and he directs early phase trials in solid tumors. So welcome.

Andrew Ohyama Parsonson: Hi, thank you for having me.

Tian Zhang: So congratulations first on the presentation of the phase I trial of DB-1311. Tell us about it and its mechanism.

Andrew Ohyama Parsonson: Yeah, thank you. So DB-1311 is a B7-H3 targeting antibody drug conjugate with a potent topoisomerase I inhibitor payload. This is a phase I and II study that's been running across the world in several centers, which is now up to approximately 12 cohorts. And particularly in ASCO 2025, we'll be focusing on the castrate resistant prostate cancer cohort and the activity in that.

Tian Zhang: And why B7-H3 as a target?

Andrew Ohyama Parsonson: Yeah, absolutely. So B7-H3 is a immunomodulatory protein. It's expressed ubiquitously in multiple tumor types and less so on normal tissue, which of course, makes it an attractive target for antibody drug conjugates. It's expressed quite widely on prostate cancer in particular. And hence, why it was often chosen as a target for a lot of antibody drug conjugate molecules.

Tian Zhang: I remember we characterized a lot of CRPC circulating tumor cells, for example, and they all had B7-H3. So highly expressed, as you say. How many patients were on this portion of the trial that you're reporting at ASCO 2025 and what did you find?

Andrew Ohyama Parsonson: So this portion of the study, we're reporting on 73 patients with castrate-resistant prostate cancer. These patients were treated in multiple different cohorts. So the phase I dose escalation backfill cohorts as well as several dose optimization cohorts. And also, the upcoming cohorts will be reporting on, which is looking at different lines of castrate-resistant prostate cancer.

Of the 73 patients, the objective response rate that was found and updated during the conference was that it showed an objective response rate of 42%, and a six-month progression-free survival of approximately 90% disease control rate as well. The general results showed that this was a relatively well-tolerated, antibody drug conjugate with largely manageable adverse effects and treatment-related adverse effects. The vast majority of patients were able to also stay on study. And there was a low discontinuation rate.

Tian Zhang: And I missed that. Can you highlight for our patients-- for our audience also that PSA response, who had PSA declines over 50%?

Andrew Ohyama Parsonson: Sure. So PSA response isn't actually reported during this meeting. So we'll be focusing on the objective response rate as well as progression-free survival.

Tian Zhang: That's great. And sometimes in our prostate cancer populations, these are patients with measurable disease that-- did all of those patients have measurable disease to come on?

Andrew Ohyama Parsonson: Yeah, thank you. So patients with bone-only evaluable disease were allowed to come on study. So those that could be evaluated with PCWG3 criteria. But there was a large proportion of patients with measurable disease. And of course, that's what's been reported with the RECIST objective response rate.

Tian Zhang: Fantastic. And it's great that it's 90% disease control rate and a good number of objective responses. That's really promising for more development. So what was particularly interesting about this drug that made you decide to open the trial?

Andrew Ohyama Parsonson: Yeah, thank you. So B7-H3 is, of course, a molecule, a target that's been looked at across several different tumor types. So certainly, this has shown activity historically in other tumor types, such as small cell lung cancer, non-small cell lung cancer.

And now, we're seeing some activity in other rarer tumors, like hepatocellular carcinoma and head and neck squamous cell carcinoma and cervical cancer. We felt that this would be a good molecule to look at and to open at our center, where we do see a vast, wide variety of solid tumors. And certainly with the amount of interest that was looked at this particular target.

Tian Zhang: Perfect. And just in general, I guess, looking especially for early phase trials, how do you decide which drugs are potentially best in class, in terms of finding the right trials to open?

Andrew Ohyama Parsonson: Yeah, that's the million dollar question, isn't it? I think that it's really hard to predict exactly which drugs might be best in class, but certainly looking at the preclinical data and the other molecules or predecessors that might have come before it, I think is always important.

And also about the company's track record always is helpful. So certainly this particular molecule that was developed by Duality Bio, there's been several other molecules that have been quite interesting and have shown activity. So this was one that we took great interest in.

Tian Zhang: Fantastic. Anything else to add for our audience?

Andrew Ohyama Parsonson: Certainly, yes. I think that the next big question in this space for, firstly, castrate-resistant prostate cancer is about sequencing and where this might fit in with the treatment. So of course, there's a lot more work to be done in this. But should this be something that's continued to be developed, where it might fit in with the multiple other treatment options that are now emerging for castrate-resistant prostate cancer?

So whether it be in the taxane naive setting, there's a cohort looking at that in the phase II setting, whether it be post lutetium, where of course, there's a great need in that setting as well, and also whether this should now be combined with other molecules and other drugs. So there's now several other studies that will be opening for not just prostate cancer, but other cancers as well. They'll be combining with immunomodulatory molecules to see whether that shows greater activity.

Tian Zhang: Fabulous. Well, I'm sure lots of clinical development to come for this molecule, given the early promising results.

Andrew Ohyama Parsonson: Absolutely.

Tian Zhang: Fantastic. Well, thank you so much for coming in.

Andrew Ohyama Parsonson: Great. Thanks so much, Tian.