On August 19, 2025 Antengene Corporation Limited ("Antengene", SEHK: 6996.HK), a leading innovative, commercial-stage global biotech company dedicated to discovering, developing and commercializing first-in-class and/or best-in-class medicines for hematologic malignancies and solid tumors, reported that its in-house discovered CLDN18.2 ADC, ATG-022,was granted a Breakthrough Therapy designation by the Center for Drug Evaluation (CDE) of the National Medical Products Administration (NMPA) for the treatment of CLDN18.2-positive, HER-2 negative unresectable or metastatic gastric or gastroesophageal junction (GC/GEJ) in patients who have received at least two prior lines of therapy (Press release, Antengene, AUG 19, 2025, View Source [SID1234655382]).

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The Breakthrough Therapy designation, introduced by the NMPA, is a key initiative aimed at accelerating the development and approval of innovative medicines that offer significant clinical benefits. With this designation, ATG-022 will receive priority review resources, reducing the overall research and development timeline and enabling faster access for patients in China. This follows the U.S. Food and Drug Administration’s (FDA) granting of Orphan Drug Designation (ODD) to ATG-022 for the treatment of gastric and pancreatic cancers, highlighting its strong clinical potential across multiple tumor types.

In the ongoing CLINCH Phase I/II clinical study, data show that ATG-022 demonstrated significant antitumor activity and a favorable safety profile in patients with gastric or gastroesophageal junction adenocarcinoma across high, low, and ultra-low CLDN18.2 expression levels.

CLDN18.2 Moderate-to-high expression (IHC 2+ > 20%)
2.4 mg/kg Cohort
Objective Response Rate (ORR): 40% (12/30), including 1 Complete Response (CR)
Disease Control Rate (DCR): 90% (27/30)
Median Progression-free Survival (mPFS): 6.97 months
6-month PFS Rate: 51.1%
9-month Overall Survival (OS) Rate: 82.7%
12-month OS Rate: 66.2%
1.8 mg/kg Cohort
ORR: 40% (10/25), including 1 CR
DCR: 84% (21/25)
CLDN18.2 Low and Ultra-low expression (IHC 2+ ≤ 20%)
Efficacious dose range of 1.8-2.4 mg/kg
ORR: 33.3% (6/18), including 1 CR
DCR: 50% (9/18)
Notably, some responding patients had CLDN18.2 expression levels below 5%, underscoring the robust antitumor activity of ATG-022 in both low- and ultra-low-expression populations.
To date, three patients in the study have achieved CR during treatment, with one case observed in each of the three aforementioned cohorts (i.e., both dose levels in the CLDN18.2 moderate-to-high expressor cohorts and the CLDN18.2 low and ultra-low expressor cohort). This broad-spectrum antitumor activity positions ATG-022 as a potential new treatment option for a wider patient population compared with other CLDN18.2-targeted therapies.

Antengene is currently conducting the Phase II dose-expansion stage of ATG-022 in the Mainland of China and Australia, with the program now entering mid-to-late stage of clinical validation. The company will continue to advance the clinical development of ATG-022 in gastric cancer while exploring its potential in other CLDN18.2-positive tumors. For gastric cancer indications, the development strategy spans first- through third-line treatment:

First-line treatment (CLDN18.2 IHC 1+ ≥1%, PD-L1 CPS ≥1%): ATG-022 in combination with pembrolizumab and chemotherapy (CAPOX/FOLFOX)
Second-line treatment (CLDN18.2 IHC 1+ ≥1%, PD-L1 CPS ≥1%): ATG-022 in combination with pembrolizumab
Third-line treatment (CLDN18.2 IHC 2+): ATG-022 monotherapy, covering patients across different CLDN18.2 expression levels, including CLDN18.2 moderate-to-high expressor (2+ >20%), and low and ultra-low expressors (2+ ≤20%)
In addition, the ongoing Phase II study includes a basket trial cohort covering multiple tumor types. In a certain subtype of gynecologic tumor, all 7 patients who had undergone at least one efficacy assessment demonstrated tumor shrinkage, indicating significant clinical potential for ATG-022 in other CLDN18.2-positive tumors. This cohort remains open for enrollment and follow-up, and the continued data generation is expected to further strengthen the robust value proposition of ATG-022 across multiple tumor types.