Darolutamide (androgen receptor inhibitor) + leuprolide + exemestane shows low ORR but 8.5-mo mPFS in AI-refractory recurrent AGCT

Darolutamide is an oral androgen receptor (AR) antagonist combined here with ovarian suppression (leuprolide acetate) plus steroidal aromatase inhibition (exemestane) in a single-arm Phase II cooperative group study (NCT06169124) enrolling recurrent adult-type ovarian granulosa cell tumor (AGCT) patients who had already progressed on a prior aromatase inhibitor. In the first-stage cohort, 17 patients enrolled (16 evaluable): ORR was 6.25% (1 PR), with 62.5% SD and 31.25% PD; median PFS was 8.5 months (95% CI 3.1–12.0) and median OS was not reached. The trial did not meet the prespecified threshold to proceed to the second stage and stopped after the initial cohort. Safety was favorable with no grade 4–5 treatment-attributable AEs; this ORR is below typical endocrine-therapy benchmarks in recurrent AGCT (e.g., anastrozole in PARAGON reported ~10.5% ORR with ~60% 6-month PFS), though the disease-stabilization rate and ~8–9 month mPFS land in a range clinicians often accept for endocrine approaches in this indolent, repeatedly relapsing tumor type.