Transcript:Vicky Makker, MD: KEYNOTE-775 is an international multicenter open-label randomized phase III trial that is evaluating the efficacy and tolerability of lenvatinib in combination with pembrolizumab versus physician’s choice chemotherapy. In this clinical trial approximately 780 patients will be accrued. Approximately 660 will be MMR [mismatch repair] proficient. Approximately 120 will be MMR deficient. Patients will be randomized 1-to-1 into 1 of 2 treatment arms. Arm 1 will be pembrolizumab in combination with lenvatinib. Pembrolizumab will be dosed at 200 mg intravenously once every 3 weeks. Lenvatinib will be dosed orally at 20 mg daily. Arm 2 will be physician’s choice chemotherapy, and the 2 choices there will be doxorubicin 60 mg/m2 intravenously every 3 weeks or weekly paclitaxel 80 mg/m2, 3 weeks on, 1 week off.
No crossover will be allowed on this clinical trial. The trial, as I mentioned, will accrue patients who are MMR proficient and also MMR deficient. There will be multiple strata in this clinical trial. The first stratum will be based on MSI [microsatellite instable] status. In the MMR-proficient group, there will be further stratifications that will include ECOG [Eastern Cooperative Oncology Group Performance Status] score, prior radiation therapy, and the region from which the patient is accrued.
The primary endpoints of this study are going to be progression-free survival by RECIST [immune-related response evaluation criteria in solid tumors] 1.1 by independent central overview, and overall survival. The secondary endpoints of this trial will include the objective response rate by blinded independent review by RECIST 1.1.
In addition, we will be evaluating quality of life using the EORTC [European Organisation for the Research and Treatment of Cancer] Quality of Life survey. And of course we’ll be evaluating safety and tolerability of this regimen. So this trial is now ongoing and accrual is occurring rapidly, and we are eagerly awaiting the results of this trial.
With regards to the treatment landscape of this disease over the next 5 years, I think that we’re going to learn a tremendous amount of information over the next 5 to 10 years, actually. So with regards to the advanced endometrial cancer space, we’re going to have the results of KEYNOTE-775 and other studies that are evaluating not only checkpoint inhibitors but combination therapies and combination checkpoint therapies. Additionally, checkpoint inhibitors in combination with antiangiogenic therapies, in combination with various targeted therapies, and PARP [poly (ADP ribose) polymerase] inhibitors I think are really going to refine the treatment landscape of the advanced endometrial cancer patient.
We’re also going to begin to see data of checkpoint inhibitors that are moving into the up-front treatment setting. So there are a number of agents that are being combined with chemotherapy, including pembrolizumab. Additionally, the frontline trial of pembrolizumab and lenvatinib versus carboplatin and paclitaxel is currently ongoing. And that data I think will really enrich our understanding as well in terms of the upfront management of endometrial cancer patients, as I think we’re really going to see an advancement in both of these arenas.
There are also studies that are now enrolling combining checkpoint inhibitors in combination with radiation therapy, which I think will inform endometrial cancer management as well. Finally, I think we really still need to understand who the optimal patients are for checkpoint therapy, checkpoint inhibitor therapy, and also combination therapies that involve checkpoint inhibitors.
We know that even patients that are microsatellite instability high don’t always respond to checkpoint inhibitors. And I think that ongoing studies are really going to help refine our understanding. So, for example, at the moment there are studies in endometrial cancers that are really evaluating tumor mutational burden as a biomarker.
Other biomarkers that are being evaluated include mutation and neoantigen load, an assessment of the RNA expression profile and other studies that again I think are going to optimize our understanding of how to funnel patients into appropriate studies and to really understand the subtypes of patients that are going to most optimally benefit from checkpoint inhibitors and other immunotherapies and combination therapies in this disease.
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Transcript Edited for Clarity.