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

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

Status

Recruiting

Phases

Phase 2

Study type

Interventional

Source

JPRN

Registry ID

JPRN-jRCT2031260183

Enrollment

Registered

2026-06-02

Start date

2026-06-15

Completion date

Unknown

Last updated

2026-06-29

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

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

Interventions

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

Eligibility

Sex/Gender

All

Inclusion criteria

Inclusion criteria: 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.

Exclusion criteria

Exclusion criteria: 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.

Design outcomes

Primary

Measure	Time frame
Progression-free survival in patients with IHH and CPS >=1	—

Contacts

Public ContactTakeru Wakatsuki

Cancer Institute Hospital of JFCR

takeru.wakatsuki@jfcr.or.jp+81-3-3520-0111

Outcome results

None listed

Source: JPRN (via WHO ICTRP) · Data processed: Jul 3, 2026