I'm delighted to be joined on UroToday with Dr. Petros Grivas, who is a medical oncologist at the University of Washington in Seattle.
Today we'll be talking about Petros' presentation at ASCO 2026, looking at subgroup analyses from the Bladder JAVELIN Medley Study, looking at sacituzumab govitecan plus avelumab.
Petros, that's a mouthful. It's always good talking to you. We got some excited data to talk about.
Petros Grivas: Wonderful to see you, Zach. Great to be at ASCO 2026 in Chicago.
Zachary Klaassen: It is.
Petros Grivas: A wealth of data across the cancers, bladder cancer. What is happening in this disease changing so rapidly?
Zachary Klaassen: It really is. We were just talking about that. This has been so exciting in the last really five years or so, just some non-muscle-invasive all the way to metastatic.
Let's talk about the JAVELIN Bladder Medley Trial. So just give our listeners just level set the high-level intention to treat population results.
Petros Grivas: Absolutely. So just to orient ourselves, so going back in time, of course, the field has changed significantly with EV pembrolizumab taking over in the frontline space.
If we go back in the pandemic era, 2020, June, we present with Professor Powles, the data from the JAVELIN Bladder 100 phase three trial that show significant overall survival and progression-free survival benefit with switch maintenance avelumab versus best supportive care alone in patients with disease control response to stable disease to platinum-based chemotherapy in the frontline setting.
So that became the standard of care at that time, and this still is an option for frontline setting, and we tried to build upon that.
So the JAVELIN Bladder Medley Trial that we recently had a publication with Dr. Jean Hoffman-Censits and the team looked at that same first-line switch-maintenance setting, patients with platinum-based chemotherapy with response to stable disease, tried to test avelumab plus combinations. And that trial, phase two trial looked at different combinations, and one of them was avelumab plus sacituzumab govitecan, let's call it SG, which is an antibody drug conjugate against Trop2, cutting a topoisomerase one inhibitor payload. Trop2 is expressed significantly in urothelial cancer cells. So an anti-Trop2 antibody drug conjugate within topoisomerase one inhibitor.
That drug combined with avelumab was compared to avelumab alone as switch-maintenance therapy for those with non-progression or prior platinum-based chemotherapy and top line this was a positive phase two trial. Avelumab plus SG significantly prolonged progression-free survival compared to avelumab alone as switch-maintenance therapy.
So it was clearly a positive phase II trial, not practice-changing, but definitely setting the stage and enthusiasm for IO plus SG combinations.
Zachary Klaassen: It's a great background because it really builds on the story. We started with avelumab and then we build on that. Then avelumab becomes a control arm. It's really clean.
When you look at the subgroup analysis, what was sort of the impetus for looking at this? What were you guys trying to look at with these subgroup analyses?
Petros Grivas: Great question, Zach. So the overall result was a positive that SG plus avelumab was better compared to avelumab alone as switch-maintenance therapy in those with response [inaudible 00:03:02] chemotherapy, and we try to look in terms of PFS. We try to look at subsets. We know that patients with visual metastasis like liver, lung, and also bone metastasis do usually worse across the board with any therapy compared to lymph node-only metastasis.
So this purpose, the impetus to your point to do this subset analysis is to look at those subsets of patients in exploratory manner. Of course, this can be underpowered to get a sense of how beneficial is a combination compared to avelumab alone across the subsets of patients.
And the take-home result was that if you look across those subsets, liver mets, lung mets, bone mets, lymph node-only metastasis across the board, the combination of avelumab plus SG was better than avelumab alone in terms of progression-free survival.
Zachary Klaassen: That's great.
Petros Grivas: And when I talk about visual or lymph node-only mets or bone mets, I talk about at the start of platinum-based chemotherapy. So before the first-line chemotherapy that was used.
Zachary Klaassen: That's great. So the take-home I see from that is it works in the intention-to-treat population. We found subgroups where it's really working for everybody.
Petros Grivas: Regardless of the site of metastasis, which has prognostic value, it seems to be that the combination is better than avelumab across the board, regardless of the site of metastasis that was present before the start of the first-line platinum-based chemotherapy.
Zachary Klaassen: Absolutely. We started this conversation with so much excitement in bladder cancer, and one of those is this EV pembrolizumab combination. So patients are now getting this as first-line treatment for metastatic urothelial.
Criteria to get SG plus avelumab is first-line platinum-based chemotherapy. So how does this fit into the whole disease space as we move forward?
Petros Grivas: Great question. So I will start by saying that this important phase two trial, Medley Trial, JAVELIN Medley Trial is positive, but it's not practice-changing. It would require probably phase three randomized larger trial for practice-changing. So it's not practice-changing, but I think it is very interesting and important for a reason that I will discuss in a second.
But backstage in a second, we talk about EV pembrolizumab that has taken over not only the first-line metastatic urothelial carcinoma, but also localized disease and is now the preferred standard of care for both the perioperative therapy setting and for frontline metastatic if it was not used before, recently at least. So EV pembrolizumab is the clearly preferred standard of care.
So the question is how do the data that I just talked about fit in that paradigm? And you may argue it's probably not immediately impacting the majority of patients.
Having said that, we're thinking about what to use after EV pembrolizumab. And after EV pembrolizumab either used in localized disease or metastatic disease, what do you do second line, third line?
In that context, we just launched a highly relevant and related phase three trial-
Zachary Klaassen: Excellent.
Petros Grivas: ... with sacituzumab govitecan with growth factor primary prophylaxis to reduce neutropenia risk plus pembrolizumab. So checkpoint inhibition plus SG combo versus platinum gemcitabine, cis-gem or cabo-gem, or taxane immunotherapy, depending on the prior therapies. And that phase three trial is for patients who had prior progression on immunotherapy, like EV pembrolizumab or whatever immunotherapy setting.
So that Medley Trial with saci-avelumab, I think indirectly raised enthusiasm for the saci-pembro trial. It's called ECOG-ACRIN 8231. It's a phase three trial through the cooperative groups and people who are listening to us hopefully can open this phase three trial, again, ECOG-ACRIN 8231, asking the checkpoint inhibitory challenge question in a patient who had progression of prior immunotherapy or exposed were, exposed to prior immunotherapy.
Zachary Klaassen: Such an exciting trial because look at where we've come in the last five years to even have this discussion that this trial is creating excitement. Again, you mentioned people should enroll to this trial.
Always a great high-level discussion, Petros. Anything we haven't hit on before we wrap up?
Petros Grivas: Great question, Zach. It's so much happening in this disease, and I'm so glad that we're discussing bladder cancer as a topic that 15 years ago was not even in the map. Now it's not only in the map, but it's probably leading drug development, I would say. And it's exciting to see options for our patients.
I would say, as I mentioned before, EV pembrolizumab, enfortumab plus pembrolizumab, is a important message to the audience is the preferred standard of care in the frontline setting is moving now to localized setting, but we definitely need better access because not all countries-
Zachary Klaassen: Great point.
Petros Grivas: ... have access or reimbursement to EV pembrolizumab. There are some countries right now in the world that EV pembrolizumab may not be available. So we have to work on increasing access, reducing and ideally eliminating healthcare disparities, but also if you have EV pembrolizumab available, what do you do next?
So I think this data I think are important and hopefully, as I mentioned, generate enthusiasm to sacituzumab govitecan-pembro trial that we have positively pembro in the US and to also help us learn more about ADC checkpoint inhibitor combination. Because it seems to be, again and again, that ADC-IO combos are very effective, and we have also published a phase two trial with saci plus pembro, a positive phase two trial for platinum-refractory disease.
So if you put everything together, I think the enthusiasm for ADC-IO combination is important. And we're not done yet. We keep going.
Zachary Klaassen: That's right. Enthusiasm is infectious. I think this is a great discussion. Thanks for joining us, Petros. Always appreciate the time.
Petros Grivas: Thank you so much for your time, Zach.