Darolutamide (AR antagonist) + leuprolide + exemestane misses ORR bar but delivers 8.5-mo mPFS in AI-refractory recurrent AGCT

Darolutamide is an androgen receptor (AR) antagonist combined here with ovarian suppression (leuprolide acetate, a GnRH agonist) and estrogen blockade (exemestane, a steroidal aromatase inhibitor) in a single-arm Phase II cooperative group study of recurrent adult-type ovarian granulosa cell tumor (AGCT) after progression on a prior aromatase inhibitor (NCT06169124). Among 17 enrolled patients, 16 were evaluable: ORR was 6.25% (1 partial response), with stable disease in 62.5% and progressive disease in 31.25%; the study stopped after stage 1 for futility per Simon’s two-stage design, despite a median PFS of 8.5 months (95% CI 3.1–12.0) and median OS not reached. Safety was favorable with no grade 4–5 treatment-attributable AEs; efficacy looks broadly in the same ballpark as prospective AI monotherapy in ER/PR+ recurrent/metastatic GCT in PARAGON (anastrozole: RECIST PR 2.6% at 12 weeks; median PFS 8.6 months), making it hard for this triplet to claim clear superiority over endocrine SOC in this niche setting.