Chapters Transcript Video Letrozole + Abemaciclib + Metformin Study Presented by Panos Konstantinopoulos, MD, PhD. Dr. Panos Konstantinopoulos presented the first study of a triplet therapy combining letrozole, abemaciclib, and metformin in any cancer type. We're very excited about this study of letrozolabemacycllib and metformin in estrogen receptor positive recurrent endometrial cancer. Uh, this builds upon our previous work, uh, in endometrial cancer where we did so that the combination of letrozole and Abemaciclib had very, very promising activity with an objective response rate of 30% and a median PFS of 9 months. However, the novo and acquired resistance still remains a challenge for this for our patients, and we wanted to build upon this um by adding a third agent in this case, metformin. I want to emphasize that this is the first study. Of this triplet combination in any cancer type we were very uh encouraged by the response we saw there were 25 patients there were a total of 32% objective response rate for um 3 complete responses and 5 partial responses and 7. And additional patients had stable disease for more than 6 months. So, uh, as, as a key takeaways, uh, for, for this if I were to summarize is that we did see, uh, a promising activity it it this threat with a triplet of letrozolabemaiclib and metformin. Uh, it is feasible, uh, tolerable, appears to induce deeper, uh, and more prolonged responses, complete responses and doubling of the PFS compared to the doublet, um, we did see, uh, some, uh, uh, uh, uh, helpful insights into who responds and who doesn't respond using uh tumor profiling, um, uh, they were a response. Even in patients who had received prior hormonal therapy, in fact, 72% of patients in our study had previously received hormonal therapy, which is very, very, uh, exciting and notable, and the PK analysis uh showed that the 500 mg of metformin is sufficient to facilitate PI3K pathway inhibition based on those prior window of opportunities studies in endometrial cancer. Published June 11, 2025 Created by Related Presenters Panos Konstantinopoulos, MD, PhD Medical Oncology View Profile