XNW27011, a Claudin 18.2(CLDN18.2) targeted antibody-drug conjugate (ADC), in patients with CLDN18.2-positive gastric/gastroesophageal junction adenocarcinoma (G/GEJA): A phase 2 study.

Abstract

3036 Background: The prognosis of G/GEJA remains poor, especially in late line patients (pts). mPFS for G/GEJA pts who received ≥ 2 prior lines of standard therapy is 1.6 - 2.6 months (mos). XNW27011 is a novel antibody-drug conjugate (ADC) targeting CLDN18.2, a promising therapeutic target that is aberrantly expressed in patients with G/GEJA. Methods: This phase 2 study aims to evaluate the efficacy and safety of XNW27011. Adult pt with advanced solid tumors who has failed standard therapy or is intolerable to available standard therapy/without available standard therapy, and with CLDN18.2 expression in ≥5% tumor cells (TC) with IHC staining ≥2+ (IHC≥2+, TC≥5%, EPR19202) were enrolled, including G/GEJA pts. All patients had measurable disease (RECIST v1.1) and ECOG 0-1. Patients received XNW27011 at 2.4-4.8 mg/kg Q3W. Endpoints included ORR for efficacy, TRAE events for safety and PK parameters. Results: As of Dec 29, 2025, a total of 86 eligible G/GEJA pts were enrolled at 2.4-4.8 mg/kg. IHC≥2+, TC≥20% was chosen as the CLDN18.2 expression criteria for further development of XNW27011. Here, we report the results in G/GEJA pts with CLDN18.2 expression of IHC≥2+, TC≥20%. Safety: 71 enrolled pts had CLDN18.2 expression of IHC≥2+, TC≥20%. The median age was 57.0 years, 87.3% of the pts had received ≥2 lines of systemic therapy, 85.9% of the pts had received immune checkpoint inhibitors. The common TRAEs (≥20%) included anemia, nausea, white blood cell count decreased, decreased appetite, neutrophil count decreased, vomiting, weight loss, hypoalbuminemia, asthenia, platelet count decreased, lymphocyte count decreased and hypokalemia. Efficacy: At 3.0 mg/kg, 26 patients were evaluable for efficacy, with 23 and 3 pts had received ≥2 and 1 prior lines of systemic therapy, respectively. The median follow-up(mFU) was 11.3 mos, cORR and cDCR were 65.4% and 84.6%, respectively. mPFS was 5.7 mos and mOS was 11.7 mos. Among the 23 pts who had ≥2 prior lines of therapy, the mPFS was 6.8 mos and mOS was 11.9 mos, with the mFU of 11.5 mos. Notably, one patient previously treated with CLDN18.2-targeted therapy still demonstrated durable clinical benefit, with PFS of 11.3 mos and still remains on treatment as of data cutoff date. Pharmacokinetics: At doses from 0.6 - 6.0 mg/kg in pts with solid tumors including G/GEJA, XNW27011 exposure (C max and AUC 0-∞ ) increased in an approximately dose proportional manner with a half-life of 5~7 days. Across all dose levels, circulating blood payload concentrations were low with 3.3% ADA positive rate. Conclusions: XNW27011 demonstrated promising anti-tumor activity and a manageable safety profile in CLDN18.2-positive G/GEJA. A pivotal phase 3 study evaluating XNW27011 as a ≥3 line therapy in G/GEJA pts is currently ongoing. Clinical trial information: NCT06792435 .