A Study of ASP2138 Together With Chemotherapy and Pembrolizumab in Adults With Gastric Cancer

NCT07673887 | Recruiting Phase 3 DMC FDA Drug

• 2 other identifiers: 2138-CL-03012025-524557-14-00
• Study Type: interventional
• Target: 570
• Locations: 1 country
• Sites: 1

Brief Summary

Claudin 18.2 or CLDN18.2 is a protein found on cells in the digestive system. It is also found in some tumors. Researchers are looking at ways to attack CLDN18.2 to help control tumors. ASP2138 is thought to bind to CLDN18.2 and a type of immune cell called a T cell. This "tells" the immune system to attack the tumor. ASP2138 is a potential treatment for people with gastric cancer (also known as stomach cancer) or gastroesophageal junction cancer (GEJ cancer). GEJ is where the tube that carries food (esophagus) joins the stomach. This study is for people with gastric or GEJ cancer that has spread nearby (locally advanced) and is not removable by surgery (unresectable), or has spread to other parts of the body (metastatic). It is for those whose cancer is human epidermal growth factor receptor 2 (HER2)-negative and CLDN18.2-positive. HER2-negative means the cancer does not have extra HER2 protein, so medicines that target HER2 do not work and are therefore not used. CLDN18.2-positive means people have a certain amount of CLDN18.2 proteins on their cancer cells. In this study, researchers want to learn if ASP2138 given together with standard treatments (chemotherapy and pembrolizumab) help people with HER2-negative and CLDN18.2-positive gastric or GEJ cancer. The main aim is to learn how long people who are given ASP2138 with chemotherapy and pembrolizumab live without their cancer getting worse, compared with placebo given with chemotherapy with or without pembrolizumab, and if they live for longer. Placebo looks like the study treatment but does not have any medicine in it. The main aim of this study is to check how well ASP2138 works when given together with chemotherapy and pembrolizumab compared with placebo plus chemotherapy with or without pembrolizumab. People aged 18 years or older with locally advanced unresectable or metastatic gastric or GEJ cancer can take part. Their tumor should be HER2-negative and CLDN18.2-positive. The study doctors will check people for any health conditions that can exclude them from taking part, interfere with the study procedures, or pose an unacceptable risk. This is a double-blind study. That means the people and the study doctors will not know who will receive which treatment. People will be assigned to one of 2 treatment groups by chance: Group A: People will receive ASP2138 along with chemotherapy and pembrolizumab. Group B: People will receive placebo along with chemotherapy, with or without pembrolizumab. People will keep receiving treatment until their cancer gets worse, they have medical problems that require stopping treatment, or a study rule says they must stop. There will be regular safety checks. People will continue to have scans of their tumor until their cancer becomes worse.

Conditions

Gastric Adenocarcinoma; Gastroesophageal Junction (GEJ) Adenocarcinoma

Keywords

Claudin (CLDN) 18.2; ASP2138; Advanced Unresectable or Metastatic Gastric Adenocarcinoma; Advanced Unresectable or Metastatic Gastroesophageal Junction (GEJ) Adenocarcinoma

Outcome Measures

Primary Outcomes (2)

• Overall Survival (OS)

  OS is defined as the time from the date of randomization until the documented date of death from any cause.

  Up to 54 months

• Progression Free Survival (PFS) per Response Evaluation Criteria in Solid Tumours Version 1.1 (RECIST V1.1) by Blinded Independent Central Review (BICR)

  PFS is defined as the time from the date of randomization until the date of radiographic disease progression per RECIST V1.1 by BICR or death from any cause, whichever is earlier.

  Up to 54 months

Secondary Outcomes (20)

• Objective response rate (ORR) per RECIST V1.1 by BICR

  Up to 54 months

• Disease control rate (DCR) per RECIST V1.1 by BICR

  Up to 54 months

• Duration of response (DOR) per RECIST V1.1 by BICR

  Up to 54 months

• PFS per RECIST V1.1 by investigator assessment

  Up to 54 months

• ORR per RECIST V1.1 by investigator assessment

  Up to 54 months

Study Arms (2)

ASP2138 in combination with pembrolizumab and chemotherapy

EXPERIMENTAL

Participants will receive ASP2138 as a subcutaneous (SC) injection either once every two weeks (Q2W) or once every three weeks (Q3W) from cycle 1 day 1 (C1D1) followed by intravenous (IV) infusion of pembrolizumab. Participants will be treated with either ASP2138 on days 1 and 22 of each cycle if receiving capecitabine and oxaliplatin (CAPOX) treatment, and on days 1, 15 and 29 of each cycle if receiving modified 5-fluorouracil, folinic acid and oxaliplatin (mFOLFOX6) treatment until discontinuation criteria are met. For all study interventions, the treatment cycle length is 42 days.

Drug: ASP2138; Drug: Pembrolizumab; Drug: Oxaliplatin; Drug: Capecitabine; Drug: Folinic acid; Drug: 5-FU

Placebo for ASP2138 in combination with pembrolizumab and chemotherapy

PLACEBO COMPARATOR

Participants will receive placebo matching ASP2138 as a SC injection either Q2W or Q3W from C1D1 followed by IV infusion of pembrolizumab or placebo matching pembrolizumab. Participants will be treated with either placebo matching ASP2138 on days 1 and 22 of each cycle if receiving CAPOX treatment, and on days 1, 15 and 29 of each cycle if receiving mFOLFOX6 treatment until discontinuation criteria are met. For all study interventions, the treatment cycle length is 42 days.

Drug: Pembrolizumab; Drug: Oxaliplatin; Drug: Capecitabine; Drug: Folinic acid; Drug: 5-FU; Drug: Placebo for ASP2138; Drug: Placebo for Pembrolizumab

Interventions

ASP2138 DRUG

SC Injection

ASP2138 in combination with pembrolizumab and chemotherapy

Pembrolizumab DRUG

IV Infusion

ASP2138 in combination with pembrolizumab and chemotherapy; Placebo for ASP2138 in combination with pembrolizumab and chemotherapy

Oxaliplatin DRUG

IV Infusion

ASP2138 in combination with pembrolizumab and chemotherapy; Placebo for ASP2138 in combination with pembrolizumab and chemotherapy

Capecitabine DRUG

Oral administration

ASP2138 in combination with pembrolizumab and chemotherapy; Placebo for ASP2138 in combination with pembrolizumab and chemotherapy

Folinic acid DRUG

IV Infusion

ASP2138 in combination with pembrolizumab and chemotherapy; Placebo for ASP2138 in combination with pembrolizumab and chemotherapy

5-FU DRUG

IV Infusion or IV bolus

ASP2138 in combination with pembrolizumab and chemotherapy; Placebo for ASP2138 in combination with pembrolizumab and chemotherapy

Placebo for ASP2138 DRUG

SC Injection

Placebo for ASP2138 in combination with pembrolizumab and chemotherapy

Placebo for Pembrolizumab DRUG

IV Infusion

Placebo for ASP2138 in combination with pembrolizumab and chemotherapy

Eligibility Criteria

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

You may qualify if:

• Participant has histologically or cytologically confirmed gastric or GEJ adenocarcinoma.
• Participant has radiographically confirmed, locally advanced unresectable or metastatic disease within 28 days prior to randomization.
• Participant has predicted life expectancy \>= 12 weeks.
• Female participant is not pregnant and at least 1 of the following conditions apply:
• Not a women of childbearing potential (WOCBP)
• WOCBP who has a negative serum pregnancy test at screening and agrees to follow the contraceptive guidance from the time of informed consent through at least 9 months after the final oxaliplatin administration and 6 months after the final administration of all other study intervention. (Note: For screening, participants with elevated serum human chorionic gonadotropin (HCG) and a demonstrated nonpregnant status through additional testing are eligible.)
• Female participant must not be breastfeeding or lactating starting at screening and throughout the investigational period, and at least 9 months after the final oxaliplatin administration and 6 months after the final administration of all other study intervention.
• Female participant must not donate ova starting at first administration of study intervention and throughout the investigational period, and for 9 months after the final oxaliplatin administration and 6 months after the final administration of all other study intervention.
• Male participant must agree to use contraception with female partner(s) of childbearing potential (including breastfeeding partner) throughout the treatment period and for 6 months after the final administration of study intervention.
• Male participant must agree to remain abstinent or use a condom with pregnant partner(s) for the duration of the pregnancy throughout the investigational period and for 6 months after the final administration of study intervention.
• Male participant must not donate sperm during the treatment period and for 6 months after the final administration of study intervention.
• Participant has radiologically evaluable disease (measurable and/or non measurable) according to RECIST V1.1, per investigator assessment, \<= 28 days prior to randomization. For participants with only 1 evaluable lesion and prior radiotherapy \<= 3 months before randomization, the lesion must either be outside the field of prior radiotherapy or have documented progression following radiation therapy.
• Participant's tumor is HER2-negative (HER2 immunohistochemistry (IHC) score 0+/1+ or HER2 IHC score 2+/in situ hybridization (ISH) negative) as determined by local or central testing.
• Participant has provided an formalin-fixed paraffin-embedded (FFPE) tumor sample which meets the requirements of the study as specified in the laboratory manual.
• Participant has CLDN18.2-positive tumor as determined by central testing.

You may not qualify if:

• Participant has mixed histology or non-adenocarcinoma gastric or GEJ cancer.
• Participant has known active central nervous system (CNS) 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 by repeat imaging (note that the repeat imaging should be performed during study screening), clinically stable and without requirement of steroid treatment for at least 14 days prior to randomization.
• Participant has gastrointestinal (GI) perforation, fistulae, untreated gastric ulcers that would preclude the participant from study participation, or any arterial thromboembolic event within 6 months, or any significant GI bleeding or any significant venous thromboembolism within 3 months prior to randomization.
• Participant has a complete gastric outlet syndrome or a partial gastric outlet syndrome with persistent/recurrent vomiting.
• Participant has pre existing peripheral neuropathy \> Grade 1.
• Participant has poorly controlled hypertension.
• Participant has significant cardiovascular disease, including any of the following:
• Congestive heart failure (defined as New York Heart Association Class III or IV), myocardial infarction, unstable angina, coronary angioplasty, stenting, coronary artery bypass graft, cerebrovascular accident or hypertensive crisis within 6 months prior to randomization.
• corrected QT (QTc) interval \> 450 msec for male participants; QTc interval \> 470 msec for female participants.
• Documented history or family history of congenital long QT syndrome.
• Cardiac arrhythmias requiring anti-arrhythmic medications (Exception: Participant with rate-controlled atrial fibrillation for \> 1 month prior to randomization is eligible), obligate use of cardiac pacemaker, or a history of clinically significant ventricular arrhythmias (i.e., sustained ventricular tachycardia, ventricular fibrillation or Torsades de Pointes).
• Participant has a diagnosis of immunodeficiency or has been diagnosed with an autoimmune disease that has required systemic treatment in past 2 years (i.e., with use of disease-modifying agents, corticosteroids or immunosuppressive drugs). Participants that require replacement therapy (e.g., thyroxine (T4), insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) may be enrolled.
• Participant has psychiatric illness or social situations that would preclude study compliance.
• Participant has history of another malignancy within 3 years prior to randomization, or any evidence of residual disease from a previously diagnosed malignancy. Participants with nonmelanoma skin cancer, localized prostate cancer treated with curative intent with no evidence of progression, low-risk or very low-risk (per standard guidelines) localized prostate cancer under active surveillance/watchful waiting without intent to treat, or carcinoma in situ of any type (if complete resection was performed) are allowed.
• Participant has history of (non-infectious) pneumonitis that required steroids, current pneumonitis, or has a history of interstitial lung disease.

Sponsors & Collaborators

• Astellas Pharma Global Development, Inc.: lead

Study Sites (1)

Pan American Center for Oncology Trials

Dorado, 00646, Puerto Rico

RECRUITING

MeSH Terms

Conditions

Adenocarcinoma

Interventions

pembrolizumab; Oxaliplatin; Capecitabine; Leucovorin; Fluorouracil

Condition Hierarchy (Ancestors)

Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Coenzymes; Enzymes and Coenzymes

Study Officials

• Development Physician

  Astellas Pharma Global Development, Inc.

  STUDY DIRECTOR

Central Study Contacts

Astellas Pharma Global Development Inc

CONTACT

800-888-7704; Astellas.registration@astellas.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 23, 2026
• First Posted: June 29, 2026
• Study Start: June 30, 2026
• Primary Completion (Estimated): February 28, 2031
• Study Completion (Estimated): February 28, 2031
• Last Updated: July 23, 2026

Record last verified: 2026-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR
• Time Frame: Access to participant level data is offered to researchers after publication of the primary manuscript (if applicable) and is available as long as Astellas has legal authority to provide the data.
• Access Criteria: Researchers must submit a proposal to conduct a scientifically relevant analysis of the study data. The research proposal is reviewed by an Independent Research Panel. If the proposal is approved, access to the study data is provided in a secure data sharing environment after receipt of a signed Data Sharing Agreement.

Locations

PR (1)