Primary Objective:~--The primary objective is to determine the efficacy (objective response rate, ORR) of the combination of DKN-01 and pembrolizumab in the treatment of women with advanced, recurrent endometrioid endometrial cancer or non-endometrioid endometrial cancer with a Wnt/ β-catenin activating mutation.~Secondary Objective:~--Estimate clinical benefit, progression-free survival, overall survival, and duration of response in patients with recurrent or progressive EC treated with DKN-01/ Pembrolizumab. To assess the tolerability of the combination.~Exploratory Objective:~We will perform the following translational studies to determine the correlation between molecular characteristics and likelihood of response to therapy. The six-month progression free survival (PFS) and the median survival from time of study entry (first treatment) to progression (PFS) or death (OS) will be estimated.~Determine if DKK1 over-expression, using RNAscope in situ hybridization performed in a central lab, is associated with CTNNB1 mutation or mutation in other genes associated with Wnt/β-catenin pathway activation. High expression of DKK1 is defined as greater than 10% positive cells on RNAscope.~Determine if mutation status of CTNNB1 or other genes known to result in activation of WNT/β-catenin signaling, such as RNF-43, APC, AXIN1/2, RSPO2/3, and ZNRF3 [1], correlate to response to the combination in women with advanced or recurrent EC. Mutation status of these genes will be determined by next-generation sequencing (Oncomine, ThermoFisher) in a CLIA- and CAP-approved Molecular Diagnostics Laboratory in the Division of Pathology & Laboratory Medicine, MD Anderson Cancer Center using formalin-fixed, paraffin-embedded tissues OR other commercially available, CLIA-certified platforms including but not limited to FoundationOne, Tempus, or CARIS. The presence of a mutation in any of these genes will be considered as indicative of Wnt/β-catenin pathway activation in a patient's tumor. Mutation status will be correlated with treatment response. Mutation status will be correlated with tumoral DKK1 expression. NGS will be performed on baseline biopsies of metastatic disease at the time of enrollment, when available, or using the primary tumor from the hysterectomy if tissue cannot be obtained or is inadequate for testing.~Determine optimal threshold of DKK1 expression and correlation to treatment response to DKN-01 and pembrolizumab.~Determine if IHC nuclear localization of mutant β-catenin correlates to treatment response to DKN-01 and pembrolizumab.~Determine if IHC CD73 expression levels correlate to treatment response to DKN-01 and pembrolizumab.~Determine if PD-L1 IHC levels correlate to treatment response.~Determine if additional genetics by NGS including but not limited to PIK3CA mutations and TMB correlate to treatment response~Determine if blood-based protein markers including but not limited to cytokines at baseline and changes on treatment correlate to response
To learn if the combination of DKN-01 and pembrolizumab can help to control advanced or recurrent endometrial cancer.