臨床研究等提出・公開システム

A Phase II Study of Zolbetuximab, Trastuzumab, and CapeOX, with Pembrolizumab Based on PD-L1 Expression, in Patients with HER2-positive and CLDN18.2-positive Advanced Gastric or Gastroesophageal Junction Cancer (ZAP-HETERO study)

A Phase II Study of Zolbetuximab, Trastuzumab, and CapeOX, with Pembrolizumab Based on PD-L1 Expression, in Patients with HER2-positive and CLDN18.2-positive Advanced Gastric or Gastroesophageal Junction Cancer

Yamaguchi Kensei

Cancer Institute Hospital of JFCR

3-8-31, Ariake, Koto, Tokyo 135-8550, Japan

kensei.yamaguchi@jfcr.or.jp

Wakatsuki Takeru

Cancer Institute Hospital of JFCR

3-8-31, Ariake, Koto, Tokyo 135-8550, Japan

+81-3-3520-0111

takeru.wakatsuki@jfcr.or.jp

Recruiting

June. 15, 2026

Interventional

single arm study

open(masking not used)

uncontrolled control

single assignment

treatment purpose

1. Subjects aged 18 years or older at the time of signing the informed consent form.
2. Subjects with histologically confirmed unresectable advanced or recurrent HER2-positive and CLDN18.2-positive gastric adenocarcinoma or gastroesophageal junction adenocarcinoma, corresponding to malignant epithelial tumors, common type, according to the 15th edition of the Japanese Classification of Gastric Carcinoma.
3. Subjects with no prior systemic therapy for gastric cancer or gastroesophageal junction cancer. However, subjects who received adjuvant chemotherapy are eligible if at least 180 days have elapsed since the last dose.
4. Availability for submission of unstained thin-section specimens, consisting of six 4-um-thick sections, prepared from the formalin-fixed paraffin-embedded (FFPE) specimen used for HER2 diagnosis.
5. Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 or 1.
6. Presence of at least one measurable lesion according to RECIST version 1.1 on CT or MRI performed within 28 days before registration.

1. Subjects with known dihydropyrimidine dehydrogenase (DPD) deficiency.
2. Subjects with a history of severe allergic reaction or intolerance to zolbetuximab or other monoclonal antibodies, pembrolizumab, or CapeOX.
3. Subjects with active bleeding from gastric cancer, gastroesophageal junction cancer, or peptic ulcer.
4. Subjects with active multiple primary cancers with a disease-free interval of less than 5 years. However, subjects with lesions confined to intramucosal carcinoma are eligible.
5. Subjects with any of the following cardiac diseases or conditions within 6 months before registration:
a. Congestive heart failure of New York Heart Association (NYHA) functional class III or higher;
b. Uncontrolled and high-risk arrhythmia;
c. History of acute coronary syndrome within 6 months;
d. Uncontrolled hypertension, defined as systolic blood pressure >=160 mmHg or diastolic blood pressure >=100 mmHg;
e. Left ventricular ejection fraction (LVEF) <50% on echocardiography (ECHO).
6. Subjects with serious comorbidities, such as interstitial pneumonia, pulmonary fibrosis, heart failure, renal failure, hepatic failure, or uncontrolled diabetes mellitus, or subjects with a history of interstitial pneumonia or pulmonary fibrosis.

Both

Patients with treatment-naive HER2-positive and CLDN18.2-positive unresectable advanced or recurrent

Zolbetuximab: 800mg/m^2 (BSA) (cycle1) 600 mg/m^2 (BSA) (cycle2) day1 q3w
Pembrolizumab: (CPS>=1) (from cycle 2) 200mg/body day1 q3w
Trastuzumab: 8mg/kg (BW) (cycle1) 6mg/kg (BW) (cycle2) day1 q3w
Oxaliplatin: 130mg/m^2 (BSA) day1 q3w
Capecitabine: 1000mg/m^2 (BSA) bid day1-14 q3w

Progression-free survival in patients with IHH and CPS >=1

+81-3-3520-0111

May. 12, 2026

No

none