Antengene Doses First Patient in Pivotal Phase III CLINCH-3 Study of CLDN18.2 ADC ATG-022
核心洞察
Antengene has dosed the first patient in China in the pivotal Phase III CLINCH-3 study of ATG-022, a CLDN18.2 (搜索) antibody-drug conjugate for advanced gastric or gastroesophageal junction adenocarcinoma (搜索).
CLINCH-3 randomizes patients to ATG-022 or investigator's choice treatment and is led by principal investigator Lin Shen of Peking University Cancer Hospital (搜索).
In Phase I/II CLINCH data at the 1.8 mg/kg recommended phase 2 dose, ATG-022 produced a 46.7% objective response rate and 86.7% disease control rate in patients with IHC 2+ 20% or greater CLDN18.2 (搜索) expression.
Antengene Corporation Limited (搜索) announced that the first patient has been dosed in China in the pivotal Phase III CLINCH-3 study of ATG-022, a CLDN18.2 (搜索) antibody-drug conjugate (ADC) being evaluated for the treatment of CLDN18.2-positive advanced gastric or gastroesophageal junction adenocarcinoma (搜索). The study is intended to generate clinical evidence supporting a future marketing approval application for ATG-022 as monotherapy in this indication.
ATG-022 previously received Breakthrough Therapy Designation from the Center for Drug Evaluation (CDE) of China's National Medical Products Administration (NMPA). According to Antengene, that designation facilitated efficient regulatory communications and supported rapid advancement of the CLINCH-3 study. The trial has been initiated in China and is planned for expansion into a multi-regional clinical trial (MRCT).
Trial Design and Leadership
CLINCH-3 is a randomized, controlled, open-label, multicenter Phase III study designed to evaluate the efficacy and safety of ATG-022 versus treatment of investigator's choice in patients with CLDN18.2 (搜索)-positive advanced gastric or gastroesophageal junction adenocarcinoma (搜索). The study is led by Professor Lin Shen of Peking University Cancer Hospital (搜索) as principal investigator.
"The dosing of the first patient in CLINCH-3 marks an important step in the clinical evaluation of ATG-022," Shen said. "Patients with advanced gastric or gastroesophageal junction adenocarcinoma (搜索) continue to face substantial unmet medical needs, particularly after disease progression on existing therapies. The antitumor efficacies and manageable safety profile observed in the Phase I/II study demonstrate therapeutic potential, supporting advancement of ATG-022 into the pivotal Phase III clinical study."
Shen added that CLINCH-3 will provide important evidence on whether ATG-022 can improve clinical outcomes for patients with CLDN18.2 (搜索)-positive disease.
Phase I/II Efficacy Data at the Recommended Dose
The initiation of the pivotal study is supported by results from the Phase I/II CLINCH studies, in which ATG-022 monotherapy showed robust efficacy and a well tolerated safety profile in advanced gastric or gastroesophageal junction adenocarcinoma (搜索).
As of a June 26, 2026 data cutoff, among patients with moderate to high CLDN18.2 (搜索) expression (IHC 2+ at 20% or greater) in the 1.8 mg/kg dose cohort, which is the recommended phase 2 dose (RP2D), the objective response rate (ORR) was 46.7% (14/30) with a confirmed ORR of 40% (12/30). The disease control rate (DCR) was 86.7% (26/30), and median overall survival (mOS) had not yet been reached after a median follow-up of 14.03 months. Multiple patients achieved complete responses.
Among patients with low or ultra-low CLDN18.2 (搜索) expression treated at the efficacious dose range of 1.8 to 2.4 mg/kg, the ORR was 28.6% (6/21) and the DCR was 52.4% (11/21).
Safety Profile
In the 1.8 mg/kg cohort, the incidence of Grade 3 or higher treatment-related adverse events (TRAEs) increased slightly from 19.4% to 21.0% compared with the December 25, 2025 data cutoff. Only 9.7% of patients experienced dose reduction due to TRAEs. Despite more than six additional months of treatment exposure and follow-up, the incidence of Grade 3 or higher TRAEs remained broadly stable in that cohort.
Antengene stated that the combination of antitumor activity, survival outcomes and tolerability positions ATG-022 as a potential best-in-disease therapy for gastric cancer (搜索) or gastroesophageal junction adenocarcinoma (搜索).
Three Parallel Development Pathways
Antengene is advancing three complementary clinical development pathways for ATG-022. CLINCH-3 provides a near-term registration pathway for ATG-022 monotherapy at the optimized RP2D of 1.8 mg/kg in third-line or later gastric and gastroesophageal junction cancer with CLDN18.2 (搜索) IHC 2+ at 20% or greater, establishing the agent in gastric cancer (搜索).
CLINCH-2 is evaluating ATG-022 in the first-line setting in combination with standard-of-care chemotherapy and anti-PD-1 therapy, targeting the broadest CLDN18.2 (搜索)-positive population starting from IHC 1+ at 1% or greater, with the goal of supporting first-line registration. The CLINCH basket trial is expanding ATG-022 beyond gastric cancer (搜索), with encouraging efficacy already observed in multiple non-gastric CLDN18.2-positive solid tumors.
Company Pipeline Context
Antengene is a commercial-stage biotech company developing therapeutics for autoimmune diseases, solid tumors and hematological malignancies. Its investigational pipeline includes ATG-022 (CLDN18.2 (搜索) ADC), ATG-037 (oral CD73 (搜索) inhibitor), ATG-101 (PD-L1 (搜索) x 4-1BB (搜索) bispecific antibody), ATG-125 (搜索) (B7-H3 (搜索) x PD-L1 bispecific ADC) and ATG-207 (搜索) (alphaCD3-TGF-beta bifunctional fusion protein), alongside T cell engager programs developed on the company's proprietary AnTenGager platform.
AnTenGager is described as a TCE 2.0 platform featuring "2+1" bivalent binding for low-expressing targets, steric hindrance masking, and proprietary CD3 (搜索) sequences with fast on/off kinetics intended to minimize cytokine release syndrome and enhance efficacy. Programs on the platform include CD19 (搜索) x CD3 (ATG-201 for B cell-related autoimmune diseases, partnered with UCB (搜索)), CDH6 (搜索) x CD3 (ATG-106 for ovarian and kidney cancer (搜索), partnered with K2 Therapeutics (搜索) established by MPM BioImpact), ALPPL2 (搜索) x CD3 (ATG-112), LY6G6D (搜索) x CD3 (ATG-110 for microsatellite-stable colorectal cancer (搜索)), GPRC5D (搜索) x CD3 (ATG-021 for multiple myeloma (搜索)), LILRB4 (搜索) x CD3 (ATG-102 for acute myeloid leukemia (搜索) and chronic myelomonocytic leukemia (搜索)) and FLT3 (搜索) x CD3 (ATG-107 for acute myeloid leukemia).
Antengene reports 35 investigational new drug approvals in the United States and Asia and new drug application approvals in 10 Asia Pacific markets. Its commercial asset XPOVIO (selinexor) is approved in the Mainland of China, Taiwan China, Hong Kong China, Macau China, South Korea, Singapore, Malaysia, Thailand, Indonesia and Australia, and is included in national insurance schemes in five of those markets.