ATG-022 Earns Breakthrough Therapy Designation in China for Advanced Gastric/GEJ Adenocarcinoma

The Center for Drug Evaluation of the National Medical Products Administration (NMPA) of China has granted breakthrough therapy designation to ATG-022, a novel claudin 18.2 (CLDN18.2)–targeted antibody-drug conjugate, for the treatment of patients with CLDN18.2-positive, HER2-negative unresectable or metastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma who have received at least 2 prior lines of therapy.1

The NMPA’s decision was based on efficacy and safety findings from the ongoing phase 1/2 CLINCH trial (NCT05718895) that showed ATG-022’s antitumor activity with a favorable safety profile across patients with moderate-to-high, low, and ultralow CLDN18.2 expression levels.

Among patients with moderate-to-high CLDN18.2 expression (immunohistochemistry [IHC] 2+ > 20%), patients in the 2.4 mg/kg cohort achieved an objective response rate (ORR) of 40% (n = 12/30), including 1 complete response (CR), and a disease control rate (DCR) of 90% (n = 27/30). The median progression-free survival (PFS) was 6.97 months, and the 6-month PFS rate was 51.1%. The 9-month overall survival (OS) rate was 82.7%, and the 12-month OS rate was 66.2%. Among patients in the 1.8 mg/kg cohort, the ORR was 40% (n = 10/25), including 1 CR, with a DCR of 84% (n = 21/25).

ATG-022 also demonstrated activity in patients with low and ultralow CLDN18.2 expression (IHC 2+ ≤ 20%) treated within the efficacious dose range of 1.8 mg/kg to 2.4 mg/kg. In this subgroup, the ORR was 33.3% (n = 6/18), including 1 CR, and the DCR was 50% (n = 9/18). Notably, responses were observed even in patients with expression levels below 5%. To date, 3 patients across the trial have achieved a CR, with 1 CR reported in each of the studied cohorts.

Phase 1 CLINCH Trial Breakdown

The phase 1 portion of the CLINCH trial was conducted in dose-escalation and dose-expansion stages.2 Eligible patients were 18 years of age or older with histologically or cytologically confirmed solid tumors who had progressed on, were intolerant to, or were not candidates for standard therapies. Additional inclusion criteria included at least 1 measurable lesion per RECIST 1.1 criteria and an ECOG performance status of 0 or 1.

In the dose-escalation phase, patients with advanced CLDN18.2-positive solid tumors were treated with ATG-022 at doses ranging from 0.3 mg/kg to 3.6 mg/kg every 3 weeks. In the dose-expansion phase, patients with CLDN18.2-positive tumors (≥ IHC 1+) received the agent at either 1.8 mg/kg or 2.4 mg/kg every 3 weeks.1,2 This portion of the trial focused on assessing efficacy and safety at the selected dose levels.

The primary end points are the incidence of dose-limiting toxicities, identification of the maximum tolerated dose, and identification of the recommended phase 2 dose.2 Secondary end points include PFS, ORR and duration of response. OS is an additional end point.

Phase 2 Dose-Expansion Details

The phase 2 dose-expansion portion of CLINCH is ongoing in mainland China and Australia, with the program now progressing into the mid-to-late stages of clinical validation.1 The overall development strategy for ATF-022 in gastric cancer spans the first- through third-line settings across multiple therapeutic combinations and as monotherapy.

In the first-line setting, ATG-022 is being studied in combination with pembrolizumab (Keytruda) and chemotherapy (CAPOX [oxaliplatin and capecitabine] or FOLFOX [folinic acid, fluorouracil, and oxaliplatin]) for patients with CLDN18.2 IHC 1+ expression of at least 1% and a PD-L1 combined positive score of at least 1%. In the second-line setting, ATG-022 is under investigation in combination with pembrolizumab in the same biomarker-defined population. In the third-line setting, ATG-022 monotherapy is being evaluated in patients with CLDN18.2 expression of IHC 2+, including moderate-to-high expressors (2+ > 20%) and those with low and ultralow expression (2+ ≤ 20%).

The phase 2 program also features a basket trial cohort assessing ATG-022 in patients with other CLDN18.2-positive solid tumors. In a subset of patients with gynecologic cancers, all 7 patients who had undergone at least 1 efficacy assessment had measurable tumor shrinkage, underscoring the agent’s potential clinical utility beyond gastric and GEJ cancers. Enrollment and follow-up for this cohort are ongoing.

References

1. Antengene’s ATG-022 (CLDN18.2 ADC) granted breakthrough therapy designation for the treatment of gastric/gastroesophageal junction adenocarcinoma. News Release. Antengene Corporation Limited. August 19, 2025. Accessed August 19, 2025. https://www.antengene.com/newsinfo/441
2. A study of ATG-022 in patients with advanced/​metastatic solid tumors (CLINCH). ClinicalTrials.gov. Updated June 5, 2025. Accessed August 19, 2025. https://clinicaltrials.gov/study/NCT05718895