Of course. So iSpy2 is a platform neoadjuvant study that was initially started in 2010 to test novel chemo and immunotherapy in patients with high-risk early-stage breast cancer that were selected specifically because they had tumors sensitive to chemo and immunotherapy. And over the last few years, we have opened the endocrine optimization pilot study within iSpy2 to really test patients who have tumors that are predicted not to benefit from chemo and immunotherapy...
Of course. So iSpy2 is a platform neoadjuvant study that was initially started in 2010 to test novel chemo and immunotherapy in patients with high-risk early-stage breast cancer that were selected specifically because they had tumors sensitive to chemo and immunotherapy. And over the last few years, we have opened the endocrine optimization pilot study within iSpy2 to really test patients who have tumors that are predicted not to benefit from chemo and immunotherapy. We learned in the screening process of iSpy2 over the last decade, really, that there are patients with hormone receptor positive HER2 negative tumors that are relatively large or even node positive and could potentially benefit from neoadjuvant therapy. However, they’re not predicted to benefit from chemo. So we studied, we created this platform study for endocrine agents for patients specifically with tumors we believe don’t benefit much from chemo immunotherapy, and we believe would be sensitive to hormone therapy. So this study studies a number of novel agents, and we presented the results of our elacestrant arms, however it was actually veptogestrin, I believe that is not the correct name of the drug and I will replace it with the correct name which I do not have. We studied patients with hormone receptor positive HER2 negative early breast cancer who had either MammaPrint low risk or MammaPrint high-risk signatures. So again, not predicted to benefit as much from chemotherapy. And patients were randomized to either the correct name of the drug which I do not have, the PROTAC ER degrader monotherapy, or in combination with abemaciclib, or in combination with the AI letrozole. So three arms. Patients were treated for a total of six months of oral therapy. Premenopausal patients received ovarian function suppression. However, in two of those arms, the premenopausal patients didn’t receive ovarian function suppression until cycle two, so that we could look at the impact without OFS in that first cycle. And what we found was that the drug is extremely active. We looked at a number of endpoints. The actual primary endpoint of the study was feasibility to see if at least 75% of patients could complete 75% of the study therapy, and that was found in all three arms. We found that Ki-67, which is the marker of proliferation with endocrine therapy, was suppressed significantly in all three arms, nearly 90% suppressed, Ki-67 under 10%. And over 50% demonstrated cell cycle arrest with Ki-67 under 2.7%, of course, highest in the abemaciclib arm. We saw significant reductions in MRI functional tumor volume, a median of about 84% reduction across the three arms, no differences between the three arms. And what was really interesting is that we found that some patients could convert from being clinically node positive to pathologically node negative, which historically we have not thought to be the case or common with neoadjuvant endocrine therapy. And we saw anywhere between 11% to 19%, depending on the arm. We looked at ctDNA in patients at baseline and over the course of the six months of therapy and found that about a third of patients had detectable ctDNA using a tumor-informed assay. And of those that were positive at baseline, over 75% of them cleared their ctDNA by the time they were ready for surgery. And that’s remarkable. I think also reassuringly, we saw that patients who were negative, who had negative ctDNA at baseline, remained negative at surgery. So there wasn’t anybody that became positive at surgery, which is, of course, very reassuring. All three arms were well-tolerated. The abemaciclib arm did have more adverse events and serious adverse events compared to the other two. However, there were no new safety signals seen in any of the arms. Over 75% were able to complete 75% of study therapy. So we believe that all three of these regimens are tolerable. But as expected, the abemaciclib arm did have more toxicity.
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