Trastuzumab Deruxtecan Plus Nivolumab Plus Capecitabine Plus Oxaliplatin for HER2 Low Gastric and Gastroesophageal Junction Adenocarcinoma

NCT07529613 | Completed Phase 1 DMC

• 1 other identifier: EPOC2203
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

To evaluate the safety and tolerability of the combination therapy of T-DXd, nivolumab, and chemotherapy in patients with untreated HER2-low gastric or gastroesophageal junction adenocarcinoma, and to determine the recommended dose. Subsequently, the efficacy and safety at the recommended dose will be assessed.

Conditions

Gastric Adenocarcinoma; Gastroesophageal Junction Adenocarcinoma

Keywords

Trastuzumab Deruxtecan; T-DXd; DS-8201a; Gastric Cancer; HER2-Low

Outcome Measures

Primary Outcomes (2)

• Incidence of DLTs in Phase Ib part

  The incidence of DLTs in each cohort will be calculated for the DLT evaluable population.

  3 weeks

• ORR in Phase II part

  The ORR is defined as the proportion of participants whose best overall response, as assessed by the principal investigator or sub-investigator according to the RECIST guidelines version 1.1, is either CR or PR.

  1 year

Secondary Outcomes (5)

• Duration of Response (DoR)

  1 year

• Disease Control Rate (DCR)

  1 year

• Progression-Free Survival (PFS)

  1 year

• Overall Survival (OS)

  1 year

• Incidence of adverse events

  1 year

Other Outcomes (2)

• HER2 expression at central review

  1 year

• Evaluation of tumor tissue biomarkers by immunohistochemistry/in situ hybridization and RNA sequencing in the PhIb and PhII cohorts

  1 year

Study Arms (1)

T-DXd plus Nivolumab, Capecitabine

EXPERIMENTAL

Drug: T-DXd; Drug: Nivolumab; Drug: Capecitabine; Drug: Oxaliplatin

Interventions

T-DXd DRUG

T-DXd (4.4mg/kg, intravenous, q3w)

T-DXd plus Nivolumab, Capecitabine

Oxaliplatin DRUG

Oxaliplatin (70mg/m2, intravenous, q3w)

T-DXd plus Nivolumab, Capecitabine

Nivolumab DRUG

Nivolumab (360 mg, intravenous, q3w)

T-DXd plus Nivolumab, Capecitabine

Capecitabine DRUG

Capecitabine (750mg/m2 twice daily, days 1-14, orally)

T-DXd plus Nivolumab, Capecitabine

Eligibility Criteria

• Age: 20 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Historical confirmation of adenocarcinoma of the gastric, gastroesophageal junction, or esophagus is considered by the investigator or subinvestigator to be unresectable advanced or recurrent.
• HER2 low expression: IHC1+, or IHC2+ and ISH negative \[FISH or DISH method\] in HER2 test of the primary lesion or metastatic lesion.
• Having one or more measurable disease as specified in RECIST Guideline version 1.1.
• Systemic treatment is untreated (local radiation and surgical treatment is acceptable).
• Age at the date of informed consent is 20 years or older.
• ECOG Performance status (PS) of 0 or 1.
• Has LVEF \>= 50% by either an echocardiogram (ECHO) or multigated acquisition (MUGA) scan within 28 days before enrollment.
• Has a corrected QT interval (QTc) =\< 470 ms in females, or QTc =\< 450 ms in males based on a 12-lead ECG screening within 28 days before enrollment (allowed on the same day of the week). \[Fridericia's correction is recommended\]
• The most recent laboratory value within 14 days before enrollment meets all of the following. (Examinations on the same day of the week 2 weeks prior to the date of enrollment are allowed.) (1)Absolute Neutrophil count =\< 1,500/mm3 (2)Hemoglobin =\< 9.0 g/dL (3)Platelet count =\< 100,000/mm3 (4)Total bilirubin =\< 1.5 mg/dL (5)AST(GOT) =\< 100 IU/L =\< 200 IU/L in the presence of hepatic involvement (6)ALT(GPT) =\< 100 IU/L =\< 200 IU/L in the presence of hepatic involvement (7)Creatinine =\< 1.5 mg/dL (8)PT(INR) \< 1.8 and aPTT \< 60 seconds
• Has adequate treatment washout period before enrollment (allowed on the same day of the week), defined as:
• i. Surgery with general anesthesia: \>= 4 weeks ii. Radiotherapy: \>= 4 weeks (including palliative stereotactic body radiation therapy to the chest; palliative stereotactic body radiation therapy to other than the chest \>= 2 weeks; abdominal vertebral bodies should be included in the abdomen).
• iii. Chloroquine and hydroxychloroquine: \>= 15 days
• No blood transfusion was performed within 7 days before registration. (Transfusions on the same day of the week prior to the day of enrollment are allowed.)
• Female of childbearing potential have a negative pregnancy test within 7 days before enrollment (allowed on the same day of the week). Male and Female of childbearing potential agree to contraception for a period (4 months for male and 7 months for Female) from informed consent to the last dose of study drug.
• Written informed consent of participation in the study has been obtained from the patient.

You may not qualify if:

• Has a prior chemotherapy for unresectable advanced or recurrent gastric/esophagogastric junction/esophageal adenocarcinoma. (Note: Patients are eligible if they have received prior preoperative or postoperative adjuvant therapy. However, treatment must have been completed at least 6 months prior to enrollment and progression must have occurred at least 6 months after completion of treatment).
• Metastases to the central nervous system have been identified. (Only if CNS involvement is clinically suspected, cerebral CT scanning or MRI confirmation is mandatory at the time of screening.).
• Has a medical history of myocardial infarction or congestive heart failure (New York Heart Association Classes II-IV) within 6 months before enrollment, corresponding to the \*\*troponin levels diagnosed as myocardial infarction as defined by the \*manufacturer within 28 days before enrollment (allowed on the same day), unstable angina, or any serious arrhythmia requiring treatment.
• \*: Manufacturer refers to a testing company used by a study implementation institution.
• \*\*: Enrollment is allowed if a subject exceeds ULN, if the subject is examined and myocardial infarction can be excluded.
• Active cancer that requires aggressive treatment, such as chemotherapy or operation
• Has serious (hospitalized) complications (intestinal palsy, intestinal obstruction, pulmonary fibrosis, diabetes mellitus that is difficult to control, heart failure, myocardial infarction, unstable angina, renal failure, liver failure, psychiatric disorders, cerebrovascular disorders, etc.)
• Grade 1 or residual adverse effects of prior therapy that have not resolved to baseline (excluding hair loss).
• Note:Participants with Grade2 chronic toxicity (Defined as no worse than Grade 2 for at least 3 months prior to enrollment and manageable with standard therapy) who are considered by the investigator to have treatment-related toxicity are eligible for enrollment.
• Chemotherapy-Induced Neuropathy
• Malaise
• Has history of gastrointestinal perforation and/or gastrointestinal fistula within 6 months before enrollment.
• Has any of the following infections:
• HBs antigen positive
• HBs antibody or HBc antibody and HBV-DNA positive

Sponsors & Collaborators

• National Cancer Center Hospital East: lead

Study Sites (1)

National Cancer Center Hospital East

Kashiwa, Chiba, 277-8577, Japan

Location

MeSH Terms

Conditions

Stomach Neoplasms

Interventions

Nivolumab; Capecitabine; Oxaliplatin

Condition Hierarchy (Ancestors)

Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Stomach Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Coordination Complexes; Organic Chemicals

Study Officials

• Kohei Shitara, MD

  National Cancer Center Hospital East

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Chief of Gastroenterology and Gastrointestinal Oncology Division

Study Record Dates

• First Submitted: April 6, 2026
• First Posted: April 14, 2026
• Study Start: December 20, 2023
• Primary Completion: December 31, 2025
• Study Completion: December 31, 2025
• Last Updated: April 14, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

JP (1)