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Dr. Paz-Ares:
This is CE on ReachMD. I am Luis Paz-Ares.
Dr. Byers:
And I'm Dr. Lauren Byers.
Dr. Paz-Ares:
We are recording this shortly after the World Lung Cancer Meeting in 2025 here in Barcelona.
So, Lauren, can you share with us some of the clinical pearls that were presentedfrom trials on B7-H3–directed ADCs in extensive-stage small cell lung cancer?
Dr. Byers:
I would be happy to. So at the World Lung Conference, I think we saw some really encouraging updated and also new data around B7-H3 targeting with antibody-drug conjugates.And so with thesetherapeutics now,we're seeing an encouragingclinical activity for these patients, both withresponse rateas well as durabilityand I think now starting to have some of the survival data also, which is looking encouraging.
This is in patients with relapsed small cell lung cancer. And these patients have historically beenvery challenging in terms offinding therapeutics that work quite well.So I think that thisreally could be anewopportunity for patients in the relapsed setting.
And a couple other things that I think with what we're seeing right now is could these potentially, in the future,replace chemotherapy and become a more targeted way of delivering chemotherapy to patients' cancers?
Dr. Paz-Ares:
Okay. So I thinklooking atthe data that you just reflected and some of the other existing data also with other ADCs in this clinical context, I could say thatsomething important would be thatI would prefer to use that in patients that have not been exposed to Topo-I inhibitors. Most of these ADCs are, of course, using a Topo-I payload. We know that small cell lung cancer is pretty sensitive to Topo-I inhibitors, butindeed, there are somecases they try to use other payloads, and using the same monoclonal antibody, their response rate is much lower. So I think it'sa good idea. But of course, that means patients that have been previously treated with topoisomerase-I inhibitors maybe are not having such a benefit.
And I really like some of the trials already ongoing in the second-line settings, such as the ifinatamab trial. But of course, there are some of those ADCs that are also being tested in the first-line setting.
I think today, maybe it's a bit more difficult to test in this clinical scenario because there are a lot of things happening there with bispecifics, the T-cell engagers, induction, or maintenance. So it's going to be a bit more difficult, but I'm sure that maybe into the future, it could be another possibility.
So with all that in mind, I suppose that another relevant clinical issue is going to be the development of some predictive biomarkers in this setting, and as of today, I don't think we have it.
Do you have any other particular input here, Lauren?
Dr. Byers:
I think you make really good points in terms of the payload and expecting cross-resistance for other ADCs that may use a different targetbut are using the same payload, that we would expectpotentially less benefit for those patients if they had already been exposed to that. So I think in the future, there will be opportunities for looking at different payloads or hitting2payloads for these patients, potentially.
The other thing from a practical perspective, for many of these patients have had priortreatment beforecoming on these studies. And so I think thinking also about how to be more proactive in terms of some of the supportive careandanticipating some of the hematologictoxicities that we know are typical with these antibody-drug conjugates, I think,will be helpfulalso for patient management.
Dr. Paz-Ares:
Okay, I thinkthis is great, but I think our time is up. So thank you very much,Lauren, for the discussion, andthanks to our audience to tuning in.
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