Chapters Transcript Video ESMO Breast Cancer 2026 Highlights: Pumitamig + DB-1305/BNT325 Harold Burstein, MD, PhD, and Ana C. Garrido-Castro, MD discuss results from the Pumitamig + DB-1305/BNT325 trial, which were presented at the 2026 ESMO Breast Cancer Congress. I'm Doctor Harold Burstein, and we're talking about highlights from the ESMO breast cancer meeting held just recently in Berlin. I'm joined by Doctor Anna Garrita Castro, one of our clinical investigators and faculty here at Dana-Farber, and today we're talking about a really interesting study looking at two novel drugs. Um, one called pumidummi, uh, and the other drug called DB1305/BNT325, which presumably, if it makes it to market, they'll come up with a more clever name than that. Uh, Anna, tell us a little bit about what this study entails and what these agents are. Alright, thanks so much. So pumidami is a bi-specific PDL1 VEGF, uh, monoclonal antibody, uh, so targeting both the immune checkpoint, uh, pathway plus, uh, the, uh, the VEGF pathway. And this drug pumitivate was explored in combination with a novel trope 2 antibody drug conjugate BNT-325, which targets trope 2 and also carries a toposomerase 1 inhibitor payload similar to the other trope 2 antibody drug conjugates that are currently available. So just to help our audience. We're hearing more and more about these biospecifics and the VEGF targeting and the dual PDL-1 blockade. We've seen some very exciting data in lung cancer for those agents, and BNT 325 is going to be a novel drug, but we should think of it like a trope 2 targeted. Sort of saccetuzumab type drug datapoumab type drug, is that where we're at. OK, so now I'm oriented to what we're talking about. So tell me just a little more about the actual study itself. So here at ESO Bres they presented the results from the phase two expansion cohort of this initial trial looking at the combination of pumidomi with BNT 325. And in this study, you can see that in the phase to expansion cohort, they enrolled patients in the first line setting with previously untreated, locally advanced, unresectable or metastatic triple negative breast cancer. And here the primary endpoint of this phase two portion was the objective response rate with the combination. So this is first line and they would have never had a prior ADC or anything like that. All right. And here what they showed was a very promising overall response rate in the 30 patients enrolled in the study. Close to 77% and you can see the waterfall plot of responses with tumor reduction in those patients with valuable disease and I think importantly also is the duration of response where most patients actually had duration of response beyond 6 months with the combination. So if you were to just benchmark this for us against other existing trope 2 ADCs in the first line, Datapoumab, stuzumab, what would you say the response rate with those agents would be by themselves? So in Ascento 3 with saccetuzumab govetecan in first line PDL1 negative disease, we saw an overall response rate of 48% with Dado-DXD in a similar previously untreated metastatic TNBC setting, response rate of 63%. These data are for the combination of trope to ADC with the bi-specific. There was also the phase 1B2 study Begonia that had a combination arm of Dapodumabexin with the PDL1 inhibitor durvalumab, and that combination yielded a response rate also similar, close to 80% as we're seeing here with this combination. I think the challenge with that. Interpreting those data and these here as well is that it's hard to tease out what's the contribution of components and how much of this response is due to the trope 2 antibody drug conjugate as opposed to the combination with the immunotherapy agent and as you said a moment ago, what seems impressive is not just the response rate itself, but sort of the depth of response. You're seeing really quite robust changes and As you pointed out, it's quite durable. So these are new drugs. There must be a lot of interest in the safety profile and the toxicity. What did they find? So with this combination, you can see that there was over 40% of grade 3 or 4 treatment related adverse events, and about 50% of patients had treatment dose reductions or treatment held throughout. Uh, the study, some of the adverse events of special interest are noted here on the right, in particular, stomatitis, which was one of the most frequent adverse events seen with, uh, with the combination, including about 17% of grade 3 stomatitis. This is slightly higher than what has been reported with DadoDXD, for example. So in trochon breast 02, we saw that the overall rate. Stomattitis was approximately 60% on study with less than 10% of grade 3 events, and I think also it will be very important to understand if there was use of primary prophylaxis of mouthwash and how that can also help mitigate some of these toxicities as seen here. What are these ocular events that they're reporting here? So with the trope 2 directed antibody drug conjugates, we have seen ocular. Surface toxicity, primarily keratitis, and that has also been reported, for example, with Dadipodumabdoxigin, and in fact with Dato DXT currently per the FDA label, it is recommended that eye drops be used 4 times per day in avoiding contact lenses to try to mitigate some of this toxicity. So similar kinds of, uh, as you say, keratitis issues as opposed to visual. Great. Well, it seems pretty exciting and What do you think the, you know, the moving forward pathway should be for drugs like this? What do you see as the schema for registrational studies? Are you more excited about these bi-specific, uh, VEGF targeted plus IO or just, uh, uh, the Begonia model? If you will, of IO with the ADC, where do you think this should go? So I think these are certainly very interesting combinations to be explored and the fact that they may be able to help overcome resistance, some of them resistance mechanisms to standard immune checkpoint inhibition. And as we see an increasing use of immunotherapy for early stage triple negative breast cancer, now with the approval of pembrolizumab for us preoperative therapy and in the adjuvant setting for those patients with higher risk, stage 2 or 3 TNBC, with this will come the question of in the advanced setting, how do we overcome resistance if there's a recurrence after treatment with a keynote 522-like regimen. Um, and so there is interest in can we use novel immunotherapy agents to help overcome that. Um, also, could this perhaps work in patients with PDL1 negative, triple negative breast cancer, where currently there isn't that approval for pembrolizumab in the advanced setting. Um, could perhaps these combinations and by specific monoclonal antibodies improve that anti-tumor immune response, even in immune cold tumors such as PDL1 negative TNBC? Well, lots more to come, obviously, new classes of drugs emerging from the data presented in Berlin at the ESM Breast Cancer Conference. I'm Hal Burstein. I've been with Ana Garrita Castro. We look forward to talking to you again soon. Thank you. Published June 29, 2026 Created by Related Presenters Ana C. Garrido-Castro, MD Medical Oncology View full profile Harold Burstein, MD, PhD Medical Oncology View Full Profile