YL205, a novel anti-Napi2b antibody drug conjugate (ADC), in patients with ovarian cancer: Preliminary result from a first-in-human trial.

Abstract

5551 Background: Sodium-dependent phosphate transport protein 2b (NaPi2b) is a rapidly internalizing sodium-phosphate transporter which is highly overexpressed in ovarian cancer (OC). The prognosis of patients (pts) with heavily pretreated ovarian cancer remains poor, highlighting a significant unmet need. YL205 is a unique antibody-drug conjugate comprising a NaPi2b-directed antibody conjugated to a potent topoisomerase 1 inhibitor payload developed with TMALIN platform. The preliminary safety and efficacy of YL205 monotherapy in ovarian cancer from a multi-center, open-label, phase I/II trial are presented. Methods: Pts with advanced solid tumors, mainly OC, who had failed standard therapy or no available standard therapy were enrolled in the trial YL205-CN-101-01. It consists of dose-escalation (BF-BOIN design), followed by dose-expansion. Pts received YL205 IV at 1.0~3.0 mg/kg once every 3 weeks. Primary objectives were to assess safety and tolerability. Results: As of the data cut-off on Dec. 12, 2025, 48 OC pts were dosed with YL205 monotherapy in China and United States with median follow up time of 5.5 months (range 0.2-17.2). Pts had median age of 54.2 yo (range 32-70), 68.8% with ECOG PS 1, 37.5% with ≥ 4 prior lines of therapy. Previous therapies included bezacizumab (89.6%), PARP inhibitors (43.8%), and mirvetuximab soravtansine (2.1%). No maximum tolerated dose (MTD) was defined. Grade 3 TRAEs occurred in 27.1% of pts. 14.6% of pts developed SAEs related to tx. The most common TRAEs were neutropenia (60.4%; G≥3: 12.5%), anaemia (60.4%, G≥3: 4.2%), nausea (47.9%, G≥3: 0), vomiting (33.3%, G≥3: 0), decreased appetite (27.1%, G≥3: 0) and thrombocytopenia (25.0%, G≥3: 6.3%) across all dose levels. Among 43 efficacy evaluable pts, confirmed ORR was 46.5% (95% CI: 31.2 – 62.3), and DCR was 95.3% (95% CI: 84.2 – 99.4). At the date cutoff, the median progression-free survival (PFS) data was immature, 62.5% (15/24) of patients with a response remain on treatment. NaPi2b expression as evaluated by H-score was found to be low (0-100) in 1 pt, medium (101-201) in 11 pts (101-200) and high (201-300) in 35 pts whose tumor tissues available at baseline. No correlation trend was observed between NaPi2b expression and response. Conclusions: YL205 demonstrated a manageable safety profile in heavily pretreated ovarian cancer patients, with preliminary efficacy observed irrespective of NaPi2b expression intensity. The promising clinical data supports further investigation of this ADC in OC. Clinical trial information: NCT06459973 .