A 46.7% objective response rate in patients with moderate-to-high CLDN18.2 expression, with median overall survival not yet reached after 14 months of follow-up, is the Phase I/II data now pushing ATG-022 into a pivotal Phase III trial. Antengene dosed the first patient in China in the CLINCH-3 study of ATG-022, its CLDN18.2 antibody-drug conjugate, targeting advanced gastric or gastroesophageal junction adenocarcinoma in patients who have progressed on at least two prior lines of therapy.
The Phase III design is randomized, open-label, and controlled, comparing ATG-022 monotherapy at the 1.8 mg/kg recommended Phase 2 dose against investigator’s choice. China’s NMPA Center for Drug Evaluation previously granted ATG-022 Breakthrough Therapy Designation for this setting, which Antengene credits for accelerating the regulatory path to this pivotal study. The trial starts in China and is planned to expand into a multi-regional format, with the accumulated data intended to support a marketing approval application for monotherapy.
The Phase I/II numbers that support this move are specific. Among the 30 patients at the 1.8 mg/kg dose with moderate-to-high CLDN18.2 expression, the confirmed ORR was 40%, the disease control rate reached 86.7%, and Grade 3 or higher treatment-related adverse events held relatively flat at 21% despite more than six additional months of follow-up since the December 2025 data cut. Only 9.7% of patients required dose reduction due to toxicity. Even in the harder-to-treat low and ultra-low CLDN18.2 expression group, roughly one in four patients (28.6%) responded. The competitive context matters here: zolbetuximab (Vyloy), approved by the FDA in late 2024, addresses first-line CLDN18.2-positive gastric cancer in combination with chemotherapy, leaving later lines as an area where options remain limited.
Antengene is running CLINCH-3 alongside two parallel programs: CLINCH-2 tests ATG-022 in the first-line setting combined with chemotherapy and anti-PD-1 therapy, and the CLINCH basket trial is generating early efficacy data in non-gastric CLDN18.2-positive solid tumors. CLINCH-3 enrollment pace, particularly the speed of expansion to sites outside China, will determine how quickly Antengene can reach the readout that would support an NMPA filing.
Jon Napitupulu is Director of Media Relations at The Clinical Trial Vanguard. Jon, a computer data scientist, focuses on the latest clinical trial industry news and trends.
