DR LOVE: I want to switch over and talk a little bit about immunotherapy. And again, there was a presentation you were involved with at ASCO looking at an interesting agent, OPT-822/OPT-821. Can you talk about what it is and what you presented?

DR RUGO: So this is a trial that was conducted as a Phase III study in Taiwan and a Phase II study in the rest of Asia and the United States, because of regulatory issues in all of the different countries, but particularly the US and Taiwan.

What we did was try and see whether or not this vaccine against a carbohydrate called Globo H, which is expressed more frequently on tumor cells, whether or not a vaccine against this carbohydrate could help to maintain stable disease in patients who already responded to either hormone therapy or chemotherapy in the metastatic setting. So patients were allowed to come on who had any subtype of breast cancer, as long as they had stable or responding disease and hadn’t received more than 3 lines of therapy. So, they couldn’t have had more than 2 progression events.

The vaccine is quite interesting, because these carbohydrates are not very immunogenic. So you have to give them with an adjuvant that stimulates the immune response. And so that’s why it’s OPT-822/821. It’s the combination with the adjuvant that actually is something saponin-based, like soap, and comes from a tree bark. And then the vaccine itself is the Globo H that’s attached to a carrier protein, keyhole limpet hemocyanin, or KLH, standard vaccine.

So there is data that this vaccine in particular can generate an immune response and that you can generate both IgM and IgG to Globo H and then to other related carbohydrates. And those other related carbohydrates may also be important.

In the trial, we found no difference in progression-free survival in the overall trial population, but when we looked at the population of patients who generated an immune response by IgG to Globo H at any time during their course of therapy, those patients did significantly better than patients receiving placebo. Interestingly, if you looked at the patients who got the vaccine who had an immune response versus those who got the vaccine and didn’t have an immune response, we actually were able to separate out a group of patients who had a very poor outcome, even worse than the placebo group.

So in the era of checkpoint blockade and other immunotherapies, it’s quite intriguing to think that we could separate out a group of patients who has a very poor outcome because they don’t respond to the vaccine at all, even compared to patients as a whole who got placebo. In the future, our next set of studies is to evaluate the adjuvant and see if you can separate out a group of patients in the placebo group as well by looking at immune response.

DR LOVE: What fraction of patients did mount an immune response?

DR RUGO: Overall, about 50% of the patients had an IgG response at some point to Globo H. And it’s actually quite interesting. We couldn’t find any other clinical characteristics — line of therapy, type of cancer, et cetera, age — but the numbers really didn’t allow us to look at the specific subset of breast cancer since only a small subset had triple-negative disease. We do have a few anecdotal patients who have remained without disease, NED, for long durations of time after being on the vaccine therapy who had triple-negative breast cancer, which is interesting.

DR LOVE: Do you think there’s a future for this particular strategy or agent?

DR RUGO: I think that we’re learning a lot more about vaccines now. I’m hopeful that there’s a future for this vaccine. And we’ll learn that in the next series of studies — I think first a series of studies to try and really understand the immune response and how that relates to outcome just as an immune response, not even focal to Globo H, and then in a Phase III trial where we study the maintenance in a larger population of patients and try and pick out the people who have an immune response early.

Genomic assays and (neo)adjuvant treatment decision-making

Early-stage breast cancer in the adjuvant and neoadjuvant settings

Management of metastatic breast cancer (mBC)

CDK4/6 inhibitors for the treatment of breast cancer

Checkpoint inhibitors and other novel immunotherapeutic approaches to breast cancer

Triple-negative and BRCA mutation-positive breast cancers