TY - JOUR T1 - 76 Patients (PTS) with recurrent gynecologic cancer whose tumors have activating wnt pathway mutations respond better to DKN-01, a DICKKOPF-1 (DKK1) inhibitor JF - International Journal of Gynecologic Cancer JO - Int J Gynecol Cancer SP - A40 LP - A41 DO - 10.1136/ijgc-2019-IGCS.76 VL - 29 IS - Suppl 3 AU - R Arend AU - C Castro AU - U Matulonis AU - E Hamilton AU - C Gunderson AU - K LyBarger AU - H Goodman AU - L Duska AU - H Mahdi AU - A ElNaggar AU - M Kagey AU - L Barroilhet AU - W Bradley AU - J Sachdev AU - D O’Malley AU - C Sirard AU - M Birrer Y1 - 2019/09/01 UR - http://ijgc.bmj.com/content/29/Suppl_3/A40.3.abstract N2 - Objectives Wnt/β-catenin signaling is frequently dysregulated in gynecologic malignancies. CTNNB1, APC and RNF43 mutations cause pathway activation; CTNNB1 stabilizing mutations lead to elevated DKK1 expression which promotes an immune suppressive tumor microenvironment. Neutralization by DKN-01 (D), a mAb against DKK1, is being tested in a phase 2 basket study.Methods Eligibility included recurrent endometrial cancer (EC) or platinum resistant/refractory ovarian cancer (OC) enriched (∼50%) for Wnt signaling-related genetic alterations. Subgroup analysis was done in pts with genetic alterations associated with activation of Wnt/β-catenin signaling (CTNNB1, APC or RNF43). Pts were assigned (MD discretion) to receive D (300 mg on Days 1 & 15) or D + paclitaxel (P) (80 mg/m2 on Days 1, 8 and 15) of a 28-day cycle. Primary endpoint is ORR; exploratory endpoints: DKK1 expression (serum/plasma/tumor), tumor genetics, infiltrating immune cells, and β-catenin IHC.Results 80 pts are enrolled: D (n=33, 19 EC, 14 OC); D + P (n=47; 28 EC, 19 OC); 18 pts with CTNNB1 (n=13), APC (n=2), RNF43 (n=2), or CTNNB1 + RNF43 (n=1). 54 pts evaluable for response (table 1). D and D + P were safe and well tolerated with no additive toxicities. The trial is ongoing; updated safety, efficacy and correlative work are pending.View this table:Abstract 76 Table 1 Conclusions D and D + P have activity in pts with recurrent gyn cancers; the role of Wnt/β-catenin pathway activation as a potential biomarker for response is currently under study. Clinical trial information: NCT03395080. ER -