YL205 (NaPi2b-targeted topo1 ADC) posts 46.5% ORR in heavily pretreated ovarian cancer

YL205 is a NaPi2b-directed antibody–drug conjugate delivering a topoisomerase I inhibitor payload (TMALIN platform) evaluated as monotherapy in the first-in-human, multicenter, open-label Phase I/II YL205-CN-101-01 trial (NCT06459973) at 1.0–3.0mg/kg IV Q3W in advanced ovarian cancer (data cutoff: Dec 12, 2025). In 48 dosed patients (median 5.5-month follow-up; 37.5% with ≥4 prior lines; prior bevacizumab 89.6%, PARPi 43.8%, prior mirvetuximab 2.1%), no MTD was reached; Grade 3 TRAEs occurred in 27.1% and related SAEs in 14.6%, with common TRAEs neutropenia (60.4%; Grade ≥3 12.5%), anemia (60.4%; Grade ≥3 4.2%), nausea (47.9%), vomiting (33.3%), and thrombocytopenia (25.0%; Grade ≥3 6.3%). Among 43 efficacy-evaluable patients, confirmed ORR was 46.5% (95% CI 31.2–62.3) and DCR 95.3% (95% CI 84.2–99.4), with mPFS immature and 62.5% (15/24) of responders still on treatment—well above typical single-agent chemo benchmarks in platinum-resistant/refractory disease (historically 12–14% ORR with agents like weekly paclitaxel/topotecan/PLD in refractory settings) and numerically higher than FRα-high mirvetuximab monotherapy in PROC (32% ORR, albeit in a biomarker-selected, 1–3 prior-line population). NaPi2b H-score was high (201–300) in most baseline samples (35/47 with tissue), but no response trend by expression level was observed.