CLARITY-Gastric 01: A randomized phase 3 study of AZD0901, a Claudin18.2 (CLDN18.2)-targeted antibody-drug conjugate, in second- or later-line (2L+) advanced gastric or gastroesophageal junction cancer (GC/GEJC).
Authors: Yelena Y. Janjigian, Kohei Shitara, Elena Elimova, Jun Zhang, Ming-Huang Chen, Elizabeth Catherine Smyth, Jeeyun Lee, Rui Miao, Silver Liu, Marielle Holmblad, Rui-Hua Xu
Journal: Journal of Clinical Oncology (2025)

TPS507 Background: GC/GEJC is the fifth most commonly diagnosed cancer and the fourth leading cause of cancer-related death worldwide (Sung H, et al. CA Cancer J Clin 2021). Prognosis is poor in GC/GEJC; median overall survival (OS) is less than 10 months in the 2L setting and less than 6 months in the 3L+ setting (Wilke H, et al. Lancet Oncol 2014; Shitara K, et al. Lancet Oncol 2018). New treatment options are needed. CLDN18.2 has emerged as a new therapeutic target in GC/GEJC. AZD0901, a potential first-in-class CLDN18.2-targeted antibody conjugated to monomethyl auristatin E via a protease cleavable linker, has demonstrated clinical activity in a Phase 1 study in advanced GC/GEJC (Xu R-H, et al, J Clin Oncol 2023). CLARITY-Gastric 01 (NCT06346392) is a randomized, open-label, sponsor-blinded, global Phase 3 study that will assess the efficacy and safety of AZD0901 versus investigator’s (INV) choice of therapy after ≥1 prior therapy for advanced GC/GEJC expressing CLDN18.2. Methods: Participants (pts) will be randomized 1:1:1 to AZD0901 dose level 1 intravenous (IV) every three weeks (Q3W; Arm 1), AZD0901 dose level 2 IV Q3W (Arm 2), or INV choice of therapy (2L: ramucirumab [ram] + paclitaxel [PTX], PTX, or docetaxel [for pts with contraindication to ram only]; 3L+: irinotecan, TAS-102 [excluding China], or apatinib [China only]; Arm 3). One AZD0901 arm (Arm 1 or Arm 2) will stop enrollment after a pre-planned dose selection decision. Randomization will continue in a 1:1 ratio to the two remaining arms (selected AZD0901 dose arm and Arm 3). Eligible pts must have histologically confirmed, unresectable, locally advanced or metastatic GC/GEJC (non-HER2+, CLDN18.2 expression). Pts must have disease progression on/after ≥1 prior regimen (including platinum-fluoropyrimidine) and have an ECOG performance status of 0 or 1. Pts previously treated with CLDN18.2-targeting therapy (other than naked monoclonal antibody) are excluded. Recruitment has begun and pts are planned to be enrolled across 16 countries in Asia, Europe, and North America. Dual primary endpoints are progression-free survival (PFS; intent-to-treat [ITT] pts) and OS (3L+ pts). The secondary endpoints include OS (ITT pts), PFS (3L+ pts), objective response rate and duration of response (ITT and 3L+ pts), and safety/tolerability. Efficacy data will be summarized and analyzed in the ITT population. All efficacy endpoints will assess the selected AZD0901 dose arm versus Arm 3. Safety and tolerability will be assessed in all pts who receive ≥1 dose of study treatment. Previously presented at European Society for Medical Oncology - Gastrointestinal Cancers Congress 2024, Final Publication Number: 495TiP, Kohei Shitara et al. Reused with permission. Clinical trial information: NCT06346392 .