ASCO 2025 | Evaluating the safety of gotistobart and 177Lu-PSMA-617 in mCRPC

With the combination, in theory, we were concerned about significant GI toxicity, and that’s because lutetium does have the capacity to cause some dyspepsia, diarrhea, and so we were worried about that. We did see colitis, but we did not see an incidence of that that was out of proportion to what you’d expect from the CTLA-4 binding antibody, which has actually been tested in hundreds of patients already in other phase one and two and now in a phase three trials and other cancer types so we were glad to see that that profile remained manageable. Logistically, of course, it is complicated when you’re talking about theranostics, but we’ve now become accustomed to this and with the new press release, Pluvicto meeting its primary endpoint, hormone-sensitive, I would argue that we’re going to have to get even more accustomed to this because theranostics are here to stay. Certainly, close collaboration with the nuclear medicine team in our hospital and across the sites is key. Logistically, we do give the immunotherapy before the lutetium is given, and that’s because of the pharmacokinetic blood-based studies that we’re doing. We want the samples, of course, to pose the lowest rates of radiation toxicity. Certainly, patients who have IRAEs after recently getting Pluvicto and need to be hospitalized, that is something that requires close collaboration with a radiation safety officer in the hospital to be sure that all of the personnel taking care of the patient have appropriate precautions and that any waste material is disposed of in a safe way. But overall, what’s looking to me like a more plausible backbone in prostate cancer is really something that we really are going to have to come to grips with, I would argue. So we really have to learn as a community to combine with lutetium and to have built infrastructure and collaborations that allow us to test multiple agents at the same time. And that’s really because lutetium does not cure, right? So we really, if we’re going to go towards curing patients, we’re likely going to have to combine with it.

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