ATG-022 plus pembrolizumab, with or without CAPOX chemotherapy, for CLDN18.2-positive, HER2-negative advanced stomach or gastroesophageal junction cancer

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 trial will try ATG-022 together with pembrolizumab, with or without CAPOX chemotherapy, to see if it helps people with CLDN 18.2-positive, HER2-negative advanced or metastatic gastric or gastroesophageal junction cancer who are PD-L1 positive.

Quick facts

• Phase: Phase1; Phase2
• Study type: Interventional
• Enrollment: 132 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Antengene Corporation (Industry-sponsored)
• Drugs / interventions: chimeric antigen receptor, immunotherapy, radiation, Pembrolizumab, Chemotherapy
• Locations: 30 sites (Hefei, Anhui and 29 other locations)
• Trial ID: NCT07327229 on ClinicalTrials.gov

What this trial studies

This Phase Ib/II study tests the safety and anti-tumor activity of ATG-022 combined with the PD-1 inhibitor pembrolizumab, delivered either alone or with CAPOX chemotherapy, in patients whose tumors express CLDN18.2, are HER2-negative, and are PD-L1 CPS≥1. Patients who have progressed after at least one prior systemic therapy will be enrolled to the ATG-022 + pembrolizumab arm, while treatment-naïve patients will be enrolled to the combination arm that adds CAPOX. The study begins with a Phase Ib dose-finding/safety portion of ATG-022 + pembrolizumab and may initiate the chemo-containing arm based on those initial data, followed by Phase II expansion cohorts to evaluate response and progression outcomes. Key entry requirements include measurable disease per RECIST v1.1 and adequate life expectancy and organ function, with tumor tissue required for biomarker confirmation.

Who should consider this trial

Good fit: Adults with unresectable or metastatic gastric or gastroesophageal junction adenocarcinoma that is CLDN18.2-positive, HER2-negative, PD-L1 CPS≥1, with measurable disease and the appropriate prior-therapy status for each arm are ideal candidates.

Not a fit: Patients whose tumors are CLDN18.2-negative, HER2-positive, PD-L1 CPS<1, those with active untreated brain metastases, or those who cannot tolerate immunotherapy or chemotherapy are unlikely to benefit from this regimen.

Why it matters

Potential benefit: If successful, this combination could shrink tumors or slow progression and offer a new targeted immunotherapy-based option for CLDN18.2-positive, HER2-negative gastric/GEJ cancer patients.

How similar studies have performed: Other CLDN18.2-directed therapies combined with chemotherapy or immune checkpoint inhibitors have shown encouraging signals in this molecular subgroup, but ATG-022 itself is a newer agent with limited published data.

Eligibility criteria

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.

Where this trial is running

Hefei, Anhui and 29 other locations

• Anhui Provincial Hospital — Hefei, Anhui, China (Not_yet_recruiting)
• The First Affiliated Hospital of Anhui Medical University — Hefei, Anhui, China (Not_yet_recruiting)
• Beijing Cancer hospital — Beijing, Beijing Municipality, China (Recruiting)
• Fujian Provincial Cnacer Hospital — Fuzhou, Fujian, China (Not_yet_recruiting)
• The First Affiliated Hospital of Xiamen University — Xiamen, Fujian, China (Not_yet_recruiting)
• Gansu Provincial Cnacer Hospital — Lanzhou, Gansu, China (Not_yet_recruiting)
• Cancer Institute&Hospital Chinese Academy of Medical Sciences — Langfang, Hebei, China (Not_yet_recruiting)
• The Fourth Hospital of Hebei Medical University — Shijiazhuang, Hebei, China (Not_yet_recruiting)
• Anyang Tumor Hospital — Anyang, Henan, China (Not_yet_recruiting)
• The First Affiliated Hospital of Henan Medical Hospital — Xinxiang, Henan, China (Not_yet_recruiting)
• Henan Cnacer Hospital — Zhengzhou, Henan, China (Not_yet_recruiting)
• The First Affiliated Hospital of Zhenghzou University — Zhengzhou, Henan, China (Not_yet_recruiting)
• Hubei Cancer Hospital — Wuhan, Hubei, China (Recruiting)
• Tongji Medical College of HUST — Wuhan, Hubei, China (Not_yet_recruiting)
• Jiangsu Province Hospital — Nanjing, Jiangsu, China (Not_yet_recruiting)
• The Second Affiliated Hospital of Soochow University — Suzhou, Jiangsu, China (Not_yet_recruiting)
• Xuzhou Central Hospital — Xuzhou, Jiangsu, China (Not_yet_recruiting)
• The First Affiliated Hospital of Nanchang University — Nanchang, Jiangxi, China (Not_yet_recruiting)
• The First Hospital of China Medical University — Shenyang, Liaoning, China (Not_yet_recruiting)
• General Hospital of Ningxia Medical University — Yinchuan, Ningxia, China (Not_yet_recruiting)
• Jinan Central Hospital — Jinan, Shandong, China (Recruiting)
• Shandong Cancer Hospital &Institue — Jinan, Shandong, China (Not_yet_recruiting)
• The Affiliated Hospital of Qingdao University — Qingdao, Shandong, China (Not_yet_recruiting)
• Tongren Hospital Shanghai Jiaotong University School of Medicine — Shanghai, Shanghai Municipality, China (Recruiting)
• Shanxi provincial cancer hospital — Taiyuan, Shanxi, China (Recruiting)
• The First Hospital of Shanxi Medical University — Taiyuan, Shanxi, China (Not_yet_recruiting)
• The First Affiliated Hospital of XI'AN Jiaotong University — Xi’an, Shanxi, China (Not_yet_recruiting)
• West China Hospital, Sichuan University — Chengdu, Sichuan, China (Recruiting)
• Tianjin Medical Universuty Cancer Institute & Hospital — Tianjin, Tianjin Municipality, China (Not_yet_recruiting)
• The First Affiliated Hospital of Xiamen University — Wenzhou, Zhejiang, China (Not_yet_recruiting)

Study contacts

• Study coordinator: Tingting Yu

Conditions Unresectable or Metastatic Gastric or Gastroesophageal Junction Adenocarcinoma