A Phase Ib/II Study of ATG-022 Plus Pembrolizumab With/Without Chemotherapy in Participants With Claudin (CLDN) 18.2-positive, HER2-negative, Unresectable or Metastatic Gastric or Gastroesophageal Junction AdenocarcinomaUnresectable or Metastatic Gastric or Gastroesophageal Junction Adenocarcinoma (CLINCH-2)

A Phase Ib/II Study of ATG-022 Plus Pembrolizumab With/Without Chemotherapy in Participants With Claudin (CLDN) 18.2-positive, HER2-negative, Unresectable or Metastatic Gastric or Gastroesophageal Junction Adenocarcinoma

This is A Phase Ib/II Study of ATG-022 Plus Pembrolizumab With/Without Chemotherapy in Participants With Claudin (CLDN) 18.2-positive, HER2-negative, Unresectable or Metastatic Gastric or Gastroesophageal Junction Adenocarcinoma

Study Overview

• Status: Recruiting
• Conditions: Unresectable or Metastatic Gastric or Gastroesophageal Junction Adenocarcinoma
• Intervention / Treatment: Drug: ATG-022; Drug: CAPOX; Drug: pembrolizumab/KEYTRUDA®

Detailed Description

This is a phase Ib/II Study of ATG-022 plus pembrolizumab with/without chemotherapy in participants with CLDN 18.2-positive, HER2-negative, PD-L1 positive (CPS≥1), unresectable or metastatic gastric or gastroesophageal junction adenocarcinoma. Both the intervention of ATG022 + Pembrolizumab (A+P) and the intervention of ATG-022 + pembrolizumab + chemotherapy (CAPOX regimen, A+P+C) consist of a Ib and II phase.

Participants with CLDN 18.2-positive, HER2-negative, PD-L1 positive (CPS≥1) advanced or metastatic gastric or gastroesophageal junction adenocarcinoma and having progressed on or after at least one prior systemic therapy, will be enrolled in the intervention of A + P.

Participants with CLDN 18.2-positive, HER2-negative, PD-L1 positive (CPS≥1) advanced or metastatic gastric or gastroesophageal junction adenocarcinoma and having not received any prior systemic therapy, will be enrolled in the intervention of A + P + C. The study will be firstly initiated from Ib of the intervention of A+P. The initiation of the intervention of A+P+C will be based on the clinical data of A+P

• Study Type: Interventional
• Enrollment (Estimated): 132
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Tingting Yu; Phone Number: 021-32501095; Email: tingting.yu@antengene.com
• Study Contact Backup: Name: Sunny He; Phone Number: 13810001510; Email: sunny.he@antengene.com

Study Locations

• China
  • Anhui
    • Hefei, Anhui, China
      • Not yet recruiting
      • The First Affiliated Hospital of Anhui Medical University
      • Contact: Kangsheng Gu
    • Hefei, Anhui, China
      • Not yet recruiting
      • Anhui Provincial Hospital
      • Contact: Gang Wang
  • Beijing Municipality
    • Beijing, Beijing Municipality, China
      • Recruiting
      • Beijing Cancer Hospital
      • Contact: Lin Shen, MD
  • Fujian
    • Fuzhou, Fujian, China
      • Not yet recruiting
      • Fujian Provincial Cnacer Hospital
      • Contact: Rongbo Lin
    • Xiamen, Fujian, China
      • Not yet recruiting
      • The First Affiliated Hospital of Xiamen University
      • Contact: Jiayi Li
  • Gansu
    • Lanzhou, Gansu, China
      • Not yet recruiting
      • Gansu Provincial Cnacer Hospital
      • Contact: Yuhua Liu
  • Hebei
    • Langfang, Hebei, China
      • Not yet recruiting
      • Cancer Institute&Hospital Chinese Academy of Medical Sciences
      • Contact: Yongkun Sun
    • Shijiazhuang, Hebei, China
      • Not yet recruiting
      • The Fourth Hospital of Hebei Medical University
      • Contact: Qun Zhao
  • Henan
    • Anyang, Henan, China
      • Not yet recruiting
      • Anyang Tumor Hospital
      • Contact: Jin Xia
    • Xinxiang, Henan, China
      • Not yet recruiting
      • The First Affiliated Hospital of Henan Medical Hospital
      • Contact: Liuzhong Yang
    • Zhengzhou, Henan, China
      • Not yet recruiting
      • Henan Cnacer Hospital
      • Contact: Xiaobing Chen
    • Zhengzhou, Henan, China
      • Not yet recruiting
      • The First Affiliated Hospital of Zhenghzou University
      • Contact: Yanru Qin
  • Hubei
    • Wuhan, Hubei, China
      • Recruiting
      • Hubei Cancer Hospital
      • Contact: Xinjun Liang
    • Wuhan, Hubei, China
      • Not yet recruiting
      • TongJi Medical College of HUST
      • Contact: Xianglin Yuan
  • Jiangsu
    • Nanjing, Jiangsu, China
      • Not yet recruiting
      • Jiangsu Province Hospital
      • Contact: Xiaofeng Chen
    • Suzhou, Jiangsu, China
      • Not yet recruiting
      • The Second Affiliated Hospital of Soochow University
      • Contact: Zhixiang Zhuang
    • Xuzhou, Jiangsu, China
      • Not yet recruiting
      • Xuzhou Central Hospital
      • Contact: Yuan Yuan
  • Jiangxi
    • Nanchang, Jiangxi, China
      • Not yet recruiting
      • The First Affiliated Hospital of Nanchang University
      • Contact: Xiaodong Peng
  • Liaoning
    • Shenyang, Liaoning, China
      • Not yet recruiting
      • The First Hospital of China Medical University
      • Contact: Funan Liu
  • Ningxia
    • Yinchuan, Ningxia, China
      • Not yet recruiting
      • General Hospital of Ningxia Medical University
      • Contact: Ping Chen
  • Shandong
    • Jinan, Shandong, China
      • Recruiting
      • Jinan Central Hospital
      • Contact: Meili Sun
    • Jinan, Shandong, China
      • Not yet recruiting
      • Shandong Cancer Hospital &Institue
      • Contact: Changzheng Li
    • Qingdao, Shandong, China
      • Not yet recruiting
      • The Affiliated Hospital Of Qingdao University
      • Contact: Jing LV
  • Shanghai Municipality
    • Shanghai, Shanghai Municipality, China
      • Recruiting
      • Tongren Hospital Shanghai Jiaotong University School of Medicine
      • Contact: Jianjun Zhang
  • Shanxi
    • Taiyuan, Shanxi, China
      • Recruiting
      • Shanxi Provincial Cancer Hospital
      • Contact: Jinfeng Ma, MD
    • Taiyuan, Shanxi, China
      • Not yet recruiting
      • The First Hospital of Shanxi Medical University
      • Contact: Yusheng Wang
    • Xi’an, Shanxi, China
      • Not yet recruiting
      • The First Affiliated Hospital of Xi'an Jiaotong University
      • Contact: Ying Kong
  • Sichuan
    • Chengdu, Sichuan, China
      • Recruiting
      • West China Hospital, Sichuan University
      • Contact: Li Zheng, MD
  • Tianjin Municipality
    • Tianjin, Tianjin Municipality, China
      • Not yet recruiting
      • Tianjin Medical Universuty Cancer Institute & Hospital
      • Contact: Ting Deng
  • Zhejiang
    • Wenzhou, Zhejiang, China
      • Not yet recruiting
      • The First Affiliated Hospital of Xiamen University
      • Contact: Yin Jin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Provision of signed and dated, written informed consent prior to any study-specific procedures, sampling, and analyses.
2. Aged ≥18 years as of the date of consent.
3. Histological or cytological confirmation of gastric cancer or gastroesophageal junction adenocarcinoma with CLDN 18.2 positive, HER2-negative and PD-L1 positive expression.
4. Archival tumor tissue sample within 36 months prior to participating in the study or newly obtained biopsy of a tumor lesion not previously irradiated should be provided for testing of CLDN 18.2 and PD-L1 expression for determining the criteria.
5. At least 1 measurable lesion per Response Evaluation Criteria In Solid Tumors (RECIST) v1.1 by investigators.
6. Estimated life expectancy of a minimum of 12 weeks.

Exclusion Criteria:

1. Known active central nervous system metastases and/or carcinomatous meningitis. Participants with previously treated brain metastases may participate provided they are radiologically stable (i.e., without evidence of progression) for at least 4 weeks as confirmed by repeat imaging performed during the study screening, are clinically stable and have not required steroid treatment for at least 14 days before the first dose of study intervention.
2. Prior exposure to CLDN 18.2 ADC, CLDN 18.2 chimeric antigen receptor T-cell immunotherapy or agents containing MMAE.
3. Prior systemic anticancer therapy including investigational agents within 4 weeks before the first dose of study treatment or within a period during which the investigational product or systemic anticancer treatment has not been cleared from the body (e.g., a period of 5 'halflives'), whichever is the most appropriate as judged by the investigator.
4. Received any prior immunotherapy and was discontinued from that treatment due to a Grade 3 or higher irAE (except endocrine disorders that can be treated with replacement therapy) or was discontinued from that treatment due to Grade 2 myocarditis or recurrent Grade 2 pneumonitis.
5. Prior radiotherapy within 4 weeks of start of study intervention, or has radiation-related toxicities, requiring corticosteroids. Two weeks or fewer of palliative radiotherapy for non- central nervous system disease is permitted. The last radiotherapy treatment must have been performed at least 7 days before the first dose of study intervention
6. Prior a live or live-attenuated vaccine within 30 days before the first dose of study intervention. Administration of killed vaccines is allowed.
7. Prior major surgery (excluding placement of vascular access) within 28 days of the first dose of study treatment or minor surgical procedures≤7 days. No waiting is required following implantable port and catheter placement.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ATG-022+pembrolizumab/KEYTRUDA®	Drug: ATG-022; 1.8mg/kg Q3W, every 21 days as one cycle; Drug: pembrolizumab/KEYTRUDA®; 20mg Q3W, every 21 days as one cycle
Active Comparator: ATG-022+pembrolizumab/KEYTRUDA®+CAPOX	Drug: ATG-022; 1.8mg/kg Q3W, every 21 days as one cycle; Drug: CAPOX; Standard Dose level for CAPOX: Capecitabine 1000 mg/m2 PO BID on Day 1-14, Oxaliplatin 130 mg/m2 IV on Day 1, Cycled every 21 days (3 weeks) for 8 cycles.; Drug: pembrolizumab/KEYTRUDA®; 20mg Q3W, every 21 days as one cycle

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
RP2D	RP2D= Recommended Phase 2 Dose	Up to 21 Days
AEs and SAEs		12 months after the last subject enrolled
DLT	Dose Limiting Toxicity	Up to 21 Days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
ORR	Overall Response Rate	12 months after the last subject enrolled
DOR	Duration of Response	12 months after the last subject enrolled
PFS	Progression Free Survival	12 months after the last subject enrolled
Plasma concentration of ATG-022 and derived PK paramete	To characterize the PK of ATG-022	One year after last patient first dose

Collaborators and Investigators

• Sponsor: Antengene Biologics Limited
• Collaborators: Merck Sharp & Dohme LLC

Study record dates

Study Major Dates

• Study Start (Actual): February 27, 2026
• Primary Completion (Estimated): September 30, 2027
• Study Completion (Estimated): April 30, 2029

Study Registration Dates

• First Submitted: December 5, 2025
• First Submitted That Met QC Criteria: December 25, 2025
• First Posted (Actual): January 8, 2026

Study Record Updates

• Last Update Posted (Actual): April 14, 2026
• Last Update Submitted That Met QC Criteria: April 13, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: pembrolizumab
• Other Study ID Numbers: ATG-022-GC-001; KEYNOTE-G37 (Other Identifier: Merck Sharp & Dohme LLC); MK-3475-G37 (Other Identifier: Merck Sharp & Dohme LLC)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No