Antengene Corporation Ltd (SEHK: 6996.HK) has dosed the first patient in the pivotal Phase III CLINCH-3 study of its CLDN18.2-targeting antibody-drug conjugate ATG-022, according to a press release. The trial targets third-line and later CLDN18.2-positive advanced gastric or gastroesophageal junction (GEJ) adenocarcinoma — a setting where no approved CLDN18.2-directed therapy currently exists.
The CLINCH-3 study is a randomized, controlled, open-label, multicenter Phase III trial comparing ATG-022 monotherapy against investigator's choice of treatment in patients whose tumors express CLDN18.2 at IHC 2+ ≥ 20%. Co-primary endpoints are progression-free survival by independent review committee and overall survival. The study initiated in China and is planned for expansion into a multi-regional clinical trial (MRCT). ATG-022 binds CLDN18.2 — a cell adhesion molecule aberrantly expressed at the tumor cell surface in gastric and other cancers — with sub-nanomolar affinity, and delivers an MMAE cytotoxic payload via a valine-citrulline linker upon internalization.
The Phase III initiation follows China's NMPA Breakthrough Therapy Designation granted to ATG-022 in August 2025 for CLDN18.2-positive, HER2-negative unresectable or metastatic gastric/GEJ adenocarcinoma after at least two prior lines of therapy, and the CDE endorsement to conduct CLINCH-3 received in May 2026. Supporting data come from the Phase I/II CLINCH study, which as of a June 26, 2026 data cutoff showed an objective response rate of 46.7% (14/30) and a disease control rate of 86.7% (26/30) in patients with moderate-to-high CLDN18.2 expression (IHC 2+ ≥ 20%) at the 1.8 mg/kg recommended Phase II dose (RP2D), with median overall survival not yet reached after a median follow-up of 14.03 months. Multiple complete responses were observed. In patients with low or ultra-low CLDN18.2 expression treated at 1.8–2.4 mg/kg, the ORR was 28.6% (6/21). Grade ≥3 treatment-related adverse events (TRAEs) at the RP2D were reported in 21% of patients, with only 9.7% requiring dose reduction. The rate remained broadly stable despite more than six additional months of treatment exposure compared with the prior December 2025 cutoff.
The competitive landscape in the CLDN18.2-directed ADC space has moved quickly. Innovent Biologics' arcotatug tavatecan (IBI343) — a CLDN18.2-directed ADC conjugated to a topoisomerase I inhibitor payload — had its NDA accepted by China's NMPA in June 2026 following a positive Phase III result in refractory gastric cancer, putting it ahead of ATG-022 in the regulatory queue in China. AstraZeneca and Lepu Biopharma's sonesitatug vedotin (CMG901/AZD0901), a CLDN18.2-directed ADC carrying an MMAE payload, reported a Phase III overall survival benefit in second-line and later CLDN18.2-positive gastric cancer in July, with a regulatory filing anticipated. Both competitors target a broadly overlapping patient population, though CLINCH-3 focuses on a third-line or later setting and a defined IHC threshold that differs from the broader eligibility used in some competing programs.