Antengene Receives NMPA Approval for Phase Ib/II Study of ATG-022 CLDN18.2 ADC in Combination with Pembrolizumab for Gastric Cancer
核心洞察
Antengene Corporation received China NMPA approval for the Phase Ib/II CLINCH-2 study evaluating ATG-022, a CLDN18.2 (搜索)-targeted antibody-drug conjugate, in combination with pembrolizumab and chemotherapy for gastric cancer (搜索).
The study will evaluate two combination regimens in patients with CLDN18.2 (搜索)-positive, HER2 (搜索)-negative, and PD-L1 (搜索)-positive unresectable or metastatic gastric cancer (搜索) or gastroesophageal junction adenocarcinoma (搜索).
Previous Phase I/II CLINCH study data demonstrated ATG-022's strong safety profile with only 18.2% grade 3+ treatment-related adverse events and 40% objective response rate at efficacious doses.
Antengene Corporation Limited (搜索) announced that the China National Medical Products Administration (搜索) (NMPA) has approved the investigational new drug (IND) application for the Phase Ib/II CLINCH-2 study evaluating ATG-022, a CLDN18.2 (搜索) antibody-drug conjugate (ADC), in combination with MSD's anti-PD-1 (搜索) therapy KEYTRUDA® (pembrolizumab) and chemotherapy. The approval marks a significant milestone for the commercial-stage biotech company's lead oncology asset in the competitive gastric cancer (搜索) treatment landscape.
Study Design and Patient Population
The CLINCH-2 study will be led by principal investigator Prof. Lin Shen at Beijing Cancer Hospital (搜索), serving as the lead trial center. The Phase Ib/II study is designed to evaluate two distinct combination regimens in patients with CLDN18.2 (搜索)-positive, HER2 (搜索)-negative, and PD-L1 (搜索)-positive (CPS≥1) unresectable or metastatic gastric cancer (搜索) or gastroesophageal junction adenocarcinoma (搜索) (GC/GEJC).
The study will assess ATG-022 in combination with pembrolizumab (A+P) as well as ATG-022 in combination with pembrolizumab plus the CAPOX chemotherapy regimen (A+P+C). The primary objective focuses on evaluating the safety and tolerability of both combination regimens, while secondary objectives include assessing preliminary antitumor activity, evaluating ATG-022's immunogenicity, and characterizing its pharmacokinetic profile.
Promising Monotherapy Data Supports Combination Approach
Updated clinical data from the Phase I/II CLINCH study of ATG-022 monotherapy, presented at the European Society for Medical Oncology Congress 2025 (ESMO 2025), demonstrated clear differentiation in both safety and efficacy profiles. In the 1.8 mg/kg dose cohort, the incidence of grade 3 or higher treatment-related adverse events was only 18.2%, representing a favorable safety profile for the ADC class.
Notably, the study observed no ocular toxicity or interstitial lung disease, with relatively low incidence of peripheral neuropathy. The efficacious doses of 1.8mg/kg and 2.4mg/kg both demonstrated an objective response rate (ORR) of 40%, providing strong validation for ATG-022's potential in combination with pembrolizumab and chemotherapy in the frontline setting.
Broad Patient Population Potential
A particularly significant finding from the CLINCH study was that antitumor activity was observed across high, medium, and low CLDN18.2 (搜索) expression levels. This supports the use of IHC 1+ ≥1% as the enrollment threshold for frontline combination therapy, indicating potential applicability to a much broader patient population compared to other CLDN18.2-targeting therapies currently in development.
Additionally, in the basket cohort of other CLDN18.2 (搜索)+ tumor types, efficacy was observed in a gynecologic tumor subtype, providing early proof of concept for potential expansion into tumor types beyond gastric cancer (搜索).
ATG-022 Development Profile
ATG-022 is a CLDN18.2 (搜索)-targeted antibody-drug conjugate with sub-nM affinity and fast internalization characteristics. Using a VC-MMAE linker-payload (DAR 4), ATG-022 has demonstrated potent activity across tumors with high, low, and ultra-low CLDN18.2 expression levels.
The compound has received significant regulatory recognition, including two Orphan Drug designations from the U.S. Food and Drug Administration (搜索) for gastric cancer (搜索) and pancreatic cancer (搜索) treatment. Additionally, ATG-022 obtained Breakthrough Therapy Designation from China's NMPA for treating CLDN18.2 (搜索)-positive, HER-2 negative unresectable or metastatic gastric or gastroesophageal junction adenocarcinoma (搜索) in patients who have received at least two prior lines of therapy.
Company Pipeline and Platform
Antengene has established itself as a global, R&D-driven, commercial-stage biotech company with a pipeline spanning from preclinical to commercial stages. The company's portfolio includes several in-house discovered programs, including ATG-022 (CLDN18.2 (搜索) ADC), ATG-037 (oral CD73 inhibitor), ATG-101 (PD-L1 (搜索) × 4-1BB bispecific antibody), ATG-031 (CD24-targeting macrophage activator), and ATG-042 (oral PRMT5-MTA inhibitor).
To date, Antengene has obtained 32 investigational new drug approvals in the U.S. and Asia, and submitted new drug applications in 11 Asia Pacific markets. The company's lead commercial asset, XPOVIO® (selinexor), is approved in multiple markets including Mainland China, Taiwan, Hong Kong, Macau, South Korea, Singapore, Malaysia, Thailand, Indonesia and Australia.
Antengene plans to continue advancing both the ongoing CLINCH study and the newly approved CLINCH-2 study, with intentions to share updated results at upcoming medical conferences to further demonstrate ATG-022's clinical potential in the competitive gastric cancer (搜索) treatment landscape.