4023 Background: Sone-Ve (AZD0901), an antibody-drug conjugate comprising an anti-CLDN18.2 antibody and monomethyl auristatin E, showed promising antitumor activity and a manageable safety profile in pts with advanced or metastatic gastric/GEJ cancers in the first-in-human study conducted in China. Methods: CLARITY-PanTumor01 is an ongoing, global, phase 2 study (NCT06219941) evaluating Sone-Ve in gastric/GEJ cancers, PDAC, and BTC outside of China. Here we report data for pts with CLDN18.2+ advanced or metastatic gastric/GEJ cancers and ≤2 lines of prior systemic therapy (substudy 1) receiving Sone-Ve 2.2 mg/kg IV Q3W (pts randomized to 1.8 mg/kg are not reported). Primary endpoints were safety and objective response rate (ORR; 30 pts were selected to estimate ORR; lack of efficacy is concluded if ≤6 confirmed responses). Secondary endpoints included duration of response (DoR) and progression-free survival (PFS). Molecular responses (MRs) based on circulating tumor DNA (ctDNA) were evaluated. Results: As of Oct 31, 2025, 67 pts received Sone-Ve 2.2 mg/kg, including 30, 31, and 6 pts from the randomized (RC), paired biopsy (PBC), and Japanese safety (JSC) cohorts, respectively. All pts had adverse events (AEs; grade ≥3 in 34.3% overall, 36.7% of the RC, and 35.5% of the PBC). The most common grade ≥3 AEs were neutrophil count decreased (7.5%), anemia (7.5%), vomiting (6.0%), and nausea (6.0%). Dose reductions were most commonly due to gastrointestinal (GI) AEs and occurred in 40.3% of pts overall, 56.7% of the RC, and 19.4% of the PBC (adoption of a 4-drug antiemetic regimen improved GI tolerability in the PBC). The ORR was 28.4% (95% CI: 18.0–40.7). Median DoR has not yet been reached. Additional data are in the Table. Among evaluable pts, 58.6% (17/29) had sufficient baseline ctDNA levels to enable MR analysis; of these, 10 (58.8%) had at least a partial MR (>50% ctDNA reduction) within 2 cycles of Sone-Ve initiation. Conclusions: Sone-Ve 2.2 mg/kg demonstrated clinically meaningful efficacy and a manageable safety profile consistent with the first-in-human study. ctDNA MRs were observed in over half the evaluable pts. Clinical trial information: NCT06219941 . RC(n=30) PBC (n=31) Total*(n=67) ORR, % (95% CI) † 26.7 (12.3–45.9) 29.0 (14.2–48.0) 28.4 (18.0–40.7) Best overall response, n (%) † Complete response Partial response Stable disease Progressive disease Not evaluable 2 (6.7)6 (20.0)14 (46.7)7 (23.3)1 (3.3) 1 (3.2)8 (25.8)18 (58.1)4 (12.9)0 3 (4.5)16 (23.9)35 (52.2)12 (17.9)1 (1.5) 6-month response rate, % (95% CI) 87.5 (38.7–98.1) NC (NC–NC) 71.9 (39.2–89.1) PFS † Events, n/N (%) Median, months (95% CI) 6-month, % (95% CI) 22/31 (71.0)4.2 (2.9–8.6)44.8 (26.5–61.6) 19/31 (61.3)3.1 (2.8–5.5)30.3 (13.3–49.3) 47/68 (69.1)4.2 (3.0–7.0)39.9 (27.7–51.9) NC, not calculable. *Includes the JSC. † Investigator-assessed per RECIST v1.1.
Shitara et al. (Wed,) studied this question.