Expression of antibody drug conjugate target antigens in ovarian sex cord stromal Tumors

Objective: The purpose of this study is to determine antibody-drug conjugate (ADC) target antigen expression in ovarian sex cord stromal tumors (SCSTs). Methods: This was a retrospective, single-institution study examining SCSTs for immunohistochemical (IHC) expression of antigens targeted by five FDA-approved ADCs (TROP-2, HER2, folate receptor alpha, nectin-4, and tissue factor) plus expression of delta-like ligand 3 (DLL3), the target of tarlatamab-dlle, a bispecific T-cell engager. Demographic and clinical information were abstracted from medical records. Differences in H-scores were evaluated using the Wilcoxon rank-sum tests and correlation between variables was assessed using Spearman's rank correlation coefficient. Results: Thirty-two SCST samples from thirty individual patients were included. The most common diagnosis was adult type granulosa cell tumor. Minimal to no staining was observed for the antigens TROP-2, HER2, folate receptor alpha, nectin-4, and DLL3. Frequent staining for tissue factor was observed in adult GCTs with a median H-score of 49.6 (interquartile range: 1.3-122.8) and 72% had ≥1% expression of tissue factor. A modest positive correlation between H-score and estrogen receptor positivity was noted (Spearman's rho = 0.49, p = 0.06). The tissue factor H-score for the single juvenile GCT was 43.2 and for the two Sertoli Leydig tumors, H-scores were 1 and 10.2. Conclusion: The pervasive absence of HER2, folate receptor alpha, DLL3, TROP-2, and nectin-4 expression in SCSTs suggests ADCs targeting these antigens may be of limited clinical benefit. The design of clinical trials investigating the use of tissue factor-targeting ADCs for the treatment of adult GCTs warrants future consideration.