A working group report from the 2024 NCI/GCSC endometrial cancer clinical trials planning meeting: refining the approach to endometrial cancer in the immunotherapy era

ABSTRACT Endometrial cancer (EC) is now the leading cause of gynecologic cancer death in the United States. Recognizing the urgent need to improve outcomes for patients diagnosed with EC, The National Cancer Institute (NCI) Gynecologic Cancer Steering Committee (GCSC) convened a Clinical Trials Planning Meeting (CTPM) on January 8th and 9th 2024, “Refining the Approach to Endometrial Cancer in the Immunotherapy Era.” Multi-disciplinary experts were charged with addressing critical challenges, to optimize treatment of EC in the new immunotherapy landscape. As part of the CTPM working groups were assembled to address several important aspects of clinical trial design. Working Group 1 (WG1) focused on translational science and was tasked with reviewing the scientific literature for data on validated discriminants of response to immunotherapy to inform trial concept development by the therapy-focused groups. The WG established that molecular subtyping of EC is now the standard approach for classifying endometrial tumors. Molecular subtyping for both prognostic and predictive applications should be considered when assessing biomarkers as well as therapeutic targets. Additionally, strategies to improve immune response like incorporation of radiation as well as therapy sequencing considerations should continue to be explored. A major key observation from WG1 was lack of validated discriminants for immunotherapy response beyond mismatch repair status and tumor mutational burden and exploration of additional discriminants of response and resistance will be critical with the increasing use of immunotherapy in EC.