Clinical Summary:

• Design/Context: This global, phase 3 trial compared adagloxad simolenin, a Globo H–targeted vaccine, plus OBI-821 against standard treatment in patients with high-risk early-stage triple-negative breast cancer.
• Key Outcomes: The vaccine did not improve progression-free or overall survival despite encouraging prior metastatic data and a favorable tolerability profile.
• Clinical Relevance: These findings highlight challenges in vaccine development for breast cancer while reinforcing the importance of patient selection, treatment timing, and evolving immunotherapy standards.

Hope Rugo, MD, City of Hope Comprehensive Cancer Center, Duarte, California, discusses results from a phase 3 trial evaluating the Globo H-targeted vaccine adagloxad simolenin in patients with high-risk early-stage triple-negative breast cancer.

Dr Rugo presented these results at the 2026 American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago, Illinois. 

Transcript:

Hello, I'm Hope Rugo, director of the women's cancers program and division chief of breast medical oncology at the City of Hope Comprehensive Cancer Center. I'm going to talk to you today about data we're presenting at ASCO about a trial using a novel vaccine, a glycoprotein targeted against the carbohydrate tuberin antigen vaccine, that we looked at in patients with high-risk early-stage triple-negative breast cancer to see if we could improve outcomes in these patients.

The important thing to keep in mind when we're talking about things like this is that we're in a time of rapid change– when we started this study, pembrolizumab was not a standard of care, we didn't even have results from KEYNOTE-522 for a treatment for patients with at least stage 2 early triple-negative breast cancer and this is now of course a standard of care almost worldwide. Pembrolizumab was added quite late into the trial and it was really only available to countries where it had already been approved. The use of pembrolizumab was in a very small fraction of patients in this trial.

The second thing which is important as we move on is that we've started to understand more about treatment timing in patients. The use of capecitabine has increased dramatically over the course of this trial. We've seen this in a trial looking at the immunotherapy drug atezolizumab where we didn't see a benefit when it was given in the preoperative and postoperative setting, unlike pembrolizumab. One of the questions that came up was the widespread use of capecitabine and whether or not that changed potentially the results that were seen.

Then lastly, I think we've learned a lot about vaccines over the many decades that vaccines have been studied in cancer. Ideally, you'd use a vaccine to prevent a cancer, but we don't know the people who are at high enough risk and we're not going to have a vaccine that just prevents all cancers– that's a big challenge. Doing all we can do to reduce known risk factors is where we are at the moment and to reduce risk factors in patients who have them. But where we could potentially use a vaccine effectively is in patients who have early stage disease where they still have some minimal residual disease that we can't detect and those patients still have a very intact immune system and we could potentially harness the host immune system by using a vaccine to try and reduce the risk of recurrence.

We have seen that using vaccines in the metastatic setting have been challenging because the tumor is downregulating the immune markers and the host immune response activity as the tumors progress, as you have increased tumor burden, as you have more treatment, and as you go from early to the metastatic setting, we definitely see a reduced host immune response.

That's why in breast cancer we only use pembrolizumab in a patient population whose tumors express PD-L1 and who have not received prior treatment. Whereas in the early stage untreated setting, we can treat everybody with pembrolizumab regardless of PD-L1 expression and the efficacy is similar, although the response to chemo is better in patients who have these immune markers.

We use data in the metastatic setting with this vaccine called Globo H to try and improve treatment outcomes in patients with high-risk early-stage triple-negative breast cancer. The data we have with adogloxide simelenin is related to a study we did, a phase 2 study in the metastatic setting. What is this vaccine? It's a carbohydrate tumor antigen, Globo H which is highly expressed in triple-negative breast cancer and it's linked to keyhold limpic hemocyanin, which is a carrier protein. This deploys T cells and enhances the humeral response, we've shown that in our phase 2 study. We also give this drug the OBI vaccine with OBI-821, which is a saponin-based adjuvant that enhances the immune response and that's common with vaccines.

In our phase 2 clinical trial, we saw that there was improved progression-free survival in a retrospective post-hoc analysis in patients who mounted an above median immune response that was measured by anti-Globo H immunoglobulin G titers compared to those patients who did not with almost a doubling of progression-free survival in these patients, and a much longer PFS than we would've expected in patients with metastatic breast cancer in this maintenance type setting. We capitalized on those data and arranged a global phase 3 clinical trial that was designed to test the vaccine and adjuvant along with standard of care treatment versus standard of care treatment in patients who had early high-risk triple-negative breast cancer.

The reason why we chose triple-negative disease is because it is an unmet need and we did see benefits in that patient population, which I think were very encouraging to us and led us to think that we might see an advantage in that population of patients. One of the areas that's important, of course, is understanding the eligibility. We chose patients who had ERPR of less than or equal to 5% and patients who had a Globo H-positive disease with an H score of 15 or higher. They also had to received at least 4 cycles of standard taxane or anthracycline-based chemotherapy and you had to have residual disease after neoadjuvant therapy with at least a centimeter of disease or at least 1 positive axillary node, or you had to have pathologic stage 2B or 3 disease treated with adjuvant chemo alone. There's a timeframe issue where you have to finish radiation etc, but all that worked okay.

There was a lot of variation in the type of chemotherapy that patients received and most patients did not receive pembrolizumab. We enrolled 575 patients all of whom had Globo H-positive disease and what we saw was that the progression-free survival and overall survival were similar between the 2 arms, almost identical. The Globo H expression score was relatively high and in terms of the clinical characteristics, we really didn't see anything different between the 2 arms, even in terms of Globo H expression, where the overall Globo H expression, if anything, was higher in the standard of care arm that may correlate with better outcome. We don't really know. If the trial's positive, you can go into a lot of details, but in this situation, I think what's important to understand is that treatment is changing and that vaccines have to really be tested in specific populations of patients where we already know what the basic treatment is. You have to be able to rapidly change the eligibility to include newer therapies and ensure that these are balanced between the arms.

For this study, we did add pembrolizumab, but again, access was an issue as well as when it was approved in different countries so it was still only a minority of patients. The vaccine was very well tolerated, which is encouraging, but I think we need probably better vaccines, good targets. I don't think the vaccine is without efficacy because we saw some in the metastatic setting, but I think the trial is difficult because of the changing treatment over time and improved outcomes for patients who have early triple-negative breast cancer with the advent of pembrolizumab treatment and improved chemotherapy regimens. We now give a 5 month or so treatment course, depending on whether you're giving your adriamycin and cyclophosphamide every 3 weeks or every 2 weeks, you really treat for 5 to 6 months, whereas we required at least 4 cycles of treatment.

I can tell you that around the world, the treatment may be quite different as well. How these all impacted our results, of course, we're not going to know. But what does this mean for vaccines overall– I still think there's a lot of excitement about vaccines and now being able to understand that we should be treating patients earlier in their disease course with vaccines, this really helps us to design better trials where we might see improvement. The other thing is having the right target. There have been vaccines studied for HER2-positive breast cancer now for some time and there is a phase 3 trial called the FLAMINGO-01 trial, which is evaluating a vaccine approach for HER2-positive high-risk disease. And I think that this is a very nice approach. We have a known target and I think if we see benefits from vaccines, the first place we're going to see them may be in HER2-positive disease.

There are new vaccines that are being developed all the time and encouraging results from some early vaccine studies in triple-negative metastatic breast cancer. The goal being that we would want to move these rapidly into the early high risk setting because this disease still represents an unmet need even with improved outcomes.

Although our trial failed to show a benefit and outcome with this vaccine, we've learned a lot about vaccines and how we may be able to improve outcomes for patients over time.

Source:

Rugo HS, Rapoport BL, Cortes J, et al. A phase 3 trial of adagloxad simolenin/OBI-821 in patients with high-risk early-stage triple-negative breast cancer. Presented at the ASCO Annual Meeting. May 29 - June 2, 2026. Chicago, Illinois. Abstract 2551.