Tecotabart vedotin in Claudin 18.2-positive advanced gastric/gastroesophageal junction cancer: A Bayesian phase 1/2 clinical trial.

BACKGROUND

Tecotabart vedotin (LM-302) is a novel antibody-drug conjugate (ADC) targeting CLDN18.2, a promising therapeutic target in gastrointestinal cancers. This phase 1/2 study evaluated the safety, pharmacokinetics, immunogenicity, and preliminary anti-tumor activity of tecotabart vedotin in patients with advanced solid tumors, with a focus on CLDN18.2-positive gastric/gastroesophageal junction (G/GEJ) cancer.

METHODS

This open-label, multicenter study utilized a Bayesian adaptive design. Phase 1 enrolled patients with advanced solid tumors; phase 2 focused on CLDN18.2-positive G/GEJ, pancreatic, biliary tract cancer, or gastrointestinal tumors with low to moderate CLDN18.2 expression. Tecotabart vedotin was administered at 0.2-2.8 mg/kg every 3 weeks (Q3W) or 1.8-2.0 mg/kg every 2 weeks (Q2W). Primary endpoints included dose-limiting toxicities (DLTs) and safety in phase 1, and objective response rate (ORR) in phase 2. Secondary endpoints included safety, pharmacokinetics, immunogenicity, and other anti-tumor activity outcomes.

RESULTS

Overall, 153 patients received tecotabart vedotin (phase 1: 38; phase 2: 115). DLTs occurred in 5 patients at higher dose levels. The maximum tolerated dose was 2.4 mg/kg Q3W; recommended phase 2 doses were 1.8 mg/kg Q2W and 2.4 mg/kg Q3W. Among 52 evaluable patients with CLDN18.2-positive G/GEJ cancer receiving 1.8 mg/kg Q2W, ORR was 32.7 % (95 % confidence interval [CI] 20.3-47.1), with median progression-free survival of 4.9 months (95 % CI 2.7-6.9), and overall survival of 10.9 months (95 % CI 9.1-17.1). Adverse events were manageable and consistent with monomethyl auristatin E-based ADCs.

CONCLUSIONS

Tecotabart vedotin demonstrated encouraging anti-tumor activity and manageable safety in CLDN18.2-positive G/GEJ cancer, supporting further clinical development in gastrointestinal malignancies.