On October 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 the latest results from the ongoing Phase I/II CLINCH study of ATG-022 (CLDN18.2 antibody-drug conjugate [ADC]), were presented in a Poster Presentation at the European Society for Medical Oncology Congress 2025 (ESMO 2025) in Berlin, Germany.
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Details of the Poster Presentation:
ATG-022 (CLDN18.2 antibody-drug conjugate)
Title: Phase I/II study of Claudin 18.2 ADC ATG-022 in patients with advanced gastric/ gastroesophageal junction cancer (CLINCH)
Abstract Number: 2907
Presentation Number: 2113P
ATG-022 and CLINCH Study Overview
ATG-022 is a CLDN18.2-targeted ADC with sub-nM affinity and fast internalization. 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.
The ongoing Phase I/II CLINCH study consists of dose escalation and dose expansion phases. In dose escalation, patients with advanced solid tumors regardless of CLDN18.2 expression receive ATG-022 once every three weeks (0.3-3.0 mg/kg Q3W) to evaluate the safety, tolerability, and pharmacokinetics; CLDN18.2-positive (≥ IHC 1+, 1%) patients are treated at 1.8 mg/kg or 2.4 mg/kg in dose expansion to evaluate the efficacy and safety.
ATG-022 has been granted two Orphan Drug designations (ODDs) by the U.S. Food and Drug Administration (FDA) for the treatment of gastric cancer and pancreatic cancer, and in August 2025 obtained Breakthrough Therapy Designation from China’s National Medical Products Administration (NMPA) for treating CLDN18.2-positive, HER-2 negative unresectable or metastatic gastric or gastroesophageal junction adenocarcinoma (GC/GEJC) who have received at least two prior lines of therapy.
Key Results from the CLINCH Study
Efficacy Data
Among GC/GEJC patients with moderate/high CLDN18.2 expression (IHC 2+ > 20%), the 2.4 mg/kg dose cohort observed 1 complete response (CR), 11 partial responses (PRs) and 15 stable diseases (SDs), resulting in an objective response rate (ORR) of 40% (12/30) and a disease control rate (DCR) of 90% (27/30). The median progression-free survival (mPFS) was 6.97 months and the 12-month overall survival (OS) rate was 66.2%. In the 1.8 mg/kg dose cohort, there were 1 CR, 9 PRs, and 11 SDs, resulting in an ORR of 40% (10/25) and a DCR of 84% (21/25).
Among GC/GEJC patients with low/ultra low CLDN18.2 expression (IHC 2+ ≤ 20%), patients treated at the efficacious dose of 1.8-2.4 mg/kg achieved 1 CR and 5 PRs, resulting in an ORR of 33.3% (6/18) and a DCR of 50% (9/18). The patient with CR has demonstrated durable response and has been on the study for over 22 months.
To date, the study has observed three CRs, one from each of the three forementioned cohorts (two dose cohorts among CLDN18.2 mid/high expressors and the cohort of low/ultra low CLDN18.2 expressors). This broad-spectrum antitumor activity indicates ATG-022’s potential as a new treatment option for a broader population of patients).
Safety Data
At 2.4 mg/kg in the dose expansion, 45.8% of patients had ≥1 treatment-emergent adverse events (TEAEs), 60.4% of patients had grade ≥3 TEAEs. The most common grade ≥3 treatment-related adverse events (TRAEs, ≥5% of patients) were neutrophil count decrease (16.7%), decreased appetite (14.6%) and anaemia (8.3%).
In the dose-expansion phase, the 1.8 mg/kg cohort demonstrated excellent safety and tolerability, with only 13.6% of patients reporting serious TEAEs and 18.2% reporting Grade ≥3 TEAEs. The favorable safety profile of this dose level support its potential use in first-line combination regimens with chemotherapy and immune checkpoint inhibitors.
No ophthalmological toxicities or interstitial lung disease have been observed.
Conclusions and Outlook
ATG-022 demonstrated a manageable safety profile and encouraging antitumor effects in GC/GEJC adenocarcinoma patients with a broad range of CLDN18.2 expressions, thus supporting further clinical investigation in patients with variable CLDN18.2 expressions. In addition to GC/GEJC, preliminary efficacy has been observed in other non-GI tumor types which will be reported at upcoming conferences.
The 2.4 mg/kg cohort showed a favorable safety profile, while the 1.8 mg/kg cohort demonstrated even better safety and tolerability. These findings provide strong support for advancing ATG-022 in combination with immune checkpoint inhibitors and chemotherapy in first-line treatment settings, paving the way to significantly expand its clinical reach and commercial potential.
The Phase II dose expansion study of ATG-022 is going smoothly in China and Australia. In parallel, Antengene is actively preparing for combination therapy studies involving ATG-022 to further advance its clinical development.
(Press release, Antengene, OCT 19, 2025, View Source [SID1234656789])