Pharmacokinetics of ZolbetuximabPhase 2ILUSTRONCT03505320

A Study of Zolbetuximab (IMAB362) in Adults With Gastric Cancer

A Phase 2 study testing zolbetuximab, oxaliplatin and leucovorin in people with Pharmacokinetics of Zolbetuximab and Gastric Cancer, run by Astellas Pharma Global Development, Inc. at 21 sites in 6 countries.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record

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Trial summary

Zolbetuximab is being studied as a treatment for people with cancer in and around the stomach or cancer where the food pipe (esophagus) joins the stomach (gastroesophageal junction cancer). Most people with this type of cancer have a protein called Claudin 18.2 in their tumor. Read more about this study

Who is it for?: Ages 18 years and older
Conditions the study is for: Pharmacokinetics of Zolbetuximab, Gastric Cancer, Gastro-esophageal Junction (GEJ) Cancer
What is being tested?: zolbetuximab, oxaliplatin and leucovorin
Type of treatment: Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 143 participants
Where: 21 sitesin 6 countries
Study dates: 29 Jun 2018to 31 May 2028
Phase: Phase 2
Are there results?: Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Female subject eligible to participate if she is not pregnant and at least one of the following conditions applies:
Not a woman of child-bearing potential (WOCBP) OR
WOCBP who agrees to follow the contraceptive guidance throughout the treatment period and for at least 9 months after the final oxaliplatin administration and 6 months after the final administration of all other study drugs.
Female subject must agree not to breastfeed starting at screening and throughout the study period, and for 6 months after the final study drug administration.
Female subject must agree not to donate ova starting at screening and throughout the study period, and for 9 months after the final oxaliplatin administration and 6 months after the final administration of all other study drugs.
A sexually active male subject with a female partner(s) who is of child-bearing potential must agree to use contraception during the treatment period and for at least 6 months after the final study drug administration.

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Male subject must agree not to donate sperm starting at screening and throughout the study period, and for 6 months after the final study drug administration.
Male subject with a pregnant or breastfeeding partner(s) must agree to remain abstinent or use a condom for the duration of the pregnancy or time partner is breastfeeding throughout the study period and for 6 months after the final study drug administration.
Subject has histologically confirmed gastric or GEJ adenocarcinoma.
Cohorts 1-4: Subject has radiographically-confirmed, locally advanced, unresectable or metastatic disease within 28 days prior to the first dose of study treatment.
Subject's tumor is positive for CLDN18.2 expression demonstrating moderate to strong membranous staining as determined by central IHC testing.
Subject agrees to not participate in another interventional study while on treatment.
Subject has ECOG performance status 0 to 1.
Subject has predicted life expectancy ≥ 12 weeks.
Subject must meet all of the following criteria based on the centrally or locally analyzed laboratory tests collected within 14 days prior to the first dose of study treatment. In case of multiple central laboratory data within this period, the most recent data should be used.
Hemoglobin (Hgb) ≥ 9 g/dL (transfusion is allowed, but post-transfusion Hgb [24 hours or later following transfusion] must be ≥ 9 g/dL)
Absolute neutrophil count (ANC) ≥ 1.5 × 109/L
Platelets ≥ 100 × 10^9/L
Albumin ≥ 2.5 g/dL
Total bilirubin ≤ 1.5 × upper limit of normal (ULN)
Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 × ULN in subjects without liver metastases (≤ 5 × ULN if liver metastases are present)
Cohorts 1-4: Estimated creatinine clearance ≥ 30 mL/min
Cohort 5: Serum creatinine ≤ 1.5 × ULN, or estimated creatinine clearance ≥ 50 mL/min for subjects with serum creatinine levels > 1.5 × ULN
Prothrombin time/international normalized ratio and partial thromboplastin time ≤ 1.5 × ULN (except for subjects receiving anticoagulation therapy)
Specific to Cohort 1A:
Subject has measurable disease according to RECIST 1.1 within 28 days prior to the first dose of study treatment per investigator assessment. For subjects with only 1 evaluable lesion and prior radiotherapy ≤ 3 months before enrollment, the lesion must either be outside the field of prior radiotherapy or must have documented progression following radiation therapy.
Subject has disease progression on or after at least 2 prior regimens for their advanced disease, including fluoropyrimidine and platinum-containing chemotherapy, and if appropriate, HER2/neu-targeted therapy and all associated side effects have resolved to grade 1 or less.
Subject must have an additional available tumor specimen collected within 3 months prior to the first dose of study treatment.
Subject must be an appropriate candidate for a tumor biopsy and is amenable to undergo a tumor biopsy during the screening period (if applicable) and treatment period as indicated in the Schedule of Assessments.
Specific to Cohort 2:
Subject has measurable disease according to RECIST 1.1 within 28 days prior to the first dose of study treatment per investigator assessment. For subjects with only 1 evaluable lesion and prior radiotherapy ≤ 3 months before enrollment, the lesion must either be outside the field of prior radiotherapy or must have documented progression following radiation therapy.
Subject has not received prior systemic anti-cancer therapy for their advanced disease (subject may have received neoadjuvant and/or fluorouracil-containing adjuvant chemotherapy as long as it has been completed ≥ 6 months before the first dose of study treatment).
Subject has a gastric or GEJ tumor that is HER2-negative as determined by local or central testing.
Subject must have an additional available tumor specimen collected within 3 months prior to the first dose of study treatment.
Subject must be an appropriate candidate for a tumor biopsy and is amenable to undergo a tumor biopsy during the screening period (if applicable) and treatment period as indicated in the Schedule of Assessments.
Specific to Cohort 3A:
Subject has radiologically evaluable disease (measurable and/or non-measurable) according to RECIST 1.1, per local assessment, ≤ 28 days prior to the first dose of study treatment. For subjects with only 1 evaluable lesion and prior radiotherapy ≤ 3 months before enrollment, the lesion must either be outside the field of prior radiotherapy or must have documented progression following radiation therapy.
Subject has disease progression on or after at least 2 prior regimens for their advanced disease, including fluoropyrimidine and platinum-containing chemotherapy, and if appropriate, HER2/neu-targeted therapy.
Subject has not received prior checkpoint inhibitor therapy.
Specific to Cohort 4A and 4B:
Subject has radiologically evaluable disease.
Subject has not received prior systemic anti-cancer therapy for their advanced disease.
Subject has a gastric or GEJ tumor that is HER2-negative as determined by local or central testing.
Subject has not received prior checkpoint inhibitor therapy.
Specific to Cohort 4B Only:
Subject must have an additional available tumor specimen collected within 3 months prior to the first dose of study treatment.
Subject must be an appropriate candidate for a tumor biopsy and is amenable to undergo a tumor biopsy during the screening period (if applicable) and treatment period.
Specific to Cohort 5 Only:
Subject has new histologically confirmed primary gastric or GEJ adenocarcinoma that is amenable to curative resection.
Subject has locoregional, resectable gastric or GEJ adenocarcinoma. GEJ may include type I-III Siewert classification. Clinical stage will be determined by endoscopic ultrasound (EUS) and/or CT or MRI. Diagnostic laparoscopy may be used as per institutional guidelines and clinical practices.
Subject meets one of the following criteria of locoregional disease by clinical TNM staging:
GEJ: cT2,N0 (high risk-lesions: ≥ 3 cm, poorly differentiated), cT1b-cT2,N+ or cT3-cT4a,Any N.
Gastric: T2 to T4a, and/or N1-3,M0.
Subject's tumor expresses CLDN18.2 in ≥ 75% of tumor cells demonstrating moderate to strong membranous staining as determined by central IHC testing

Who cannot join

Subject has had prior severe allergic reaction or intolerance to known ingredients of zolbetuximab or other monoclonal antibodies, including humanized or chimeric antibodies.
Subject has known immediate or delayed hypersensitivity or contraindication to any component of study treatment.
Subject has received other investigational agents or devices concurrently or within 28 days prior to first dose of study treatment.
Subject has received systemic immunosuppressive therapy, including systemic corticosteroids 14 days prior to first dose of study treatment.
Subject has a complete gastric outlet syndrome or a partial gastric outlet syndrome with persistent recurrent vomiting.
Subject has significant gastric bleeding and/or untreated gastric ulcers that would preclude the subject from participation.

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Subject has history of central nervous system metastases and/or carcinomatous meningitis from gastric/GEJ cancer.
Subject has a known history of a positive test for human immunodeficiency virus (HIV) infection or known active hepatitis B (positive hepatitis B surface antigen [HBsAg]) or hepatitis C infection.
Subject has had within 6 months prior to first dose of study treatment any of the following: unstable angina, myocardial infarction, ventricular arrhythmia requiring intervention or hospitalization for heart failure.
Subject has active infection requiring systemic therapy that has not completely resolved within 7 days prior to the start of study treatment.
Subject has active autoimmune disease that has required systemic treatment within the past 3 months prior to the start of study treatment.
Subject has a clinically significant disease or co-morbidity that may adversely affect the safe delivery of treatment within this study or make the subject unsuitable for study participation.
Subject has psychiatric illness or social situations that would preclude study compliance.
Subject has had a major surgical procedure ≤ 28 days before start of study treatment.
Subject is without complete recovery from a major surgical procedure ≤ 14 days before start of study treatment
Subject has received radiotherapy for locally advanced unresectable or metastatic gastric or GEJ adenocarcinoma ≤ 14 days (Cohorts 1 and 3A) and ≤ 28 days (Cohorts 2 and 4A or 4B) prior to start of study treatment and has NOT recovered from any related toxicity.
Subject has another malignancy, for which treatment is required.
Cohort 2, 4 and 5 Only, subject has any of the following:
Prior severe allergic reaction or intolerance to any component of mFOLFOX6 or FLOT chemotherapeutics in this study
Known dihydropyrimidine dehydrogenase deficiency (DPD).
Known peripheral neuropathy > Grade 1 (absence of deep tendon reflexes as the sole neurological abnormality does not render the subject ineligible).
Sinusoidal obstruction syndrome, formerly known as veno-occlusive disease, if present, should be stable or improving.
History of clinically significant ventricular arrhythmias.
QTc interval > 450 msec for male subjects; QTc interval > 470 msec for female subjects.
History or family history of congenital long QT syndrome.
Cardiac arrhythmias requiring anti-arrhythmic medications (Subjects with rate controlled atrial fibrillation for > 1 month prior to first dose of study treatment are eligible).
Cohorts 3A, 4A and 4B Only, subject has any of the following:
Ongoing or previous autoimmune disease or interstitial lung disease, active diverticulitis or gastrointestinal ulcerative disease, or solid organ or stem cell transplant (for Cohort 4) or other uncontrolled or clinically significant medical disorders.
Type 1 diabetes mellitus, endocrinopathies stably maintained on appropriate replacement therapy or skin disorders (e.g., vitiligo, psoriasis, or alopecia) not requiring systemic treatment are allowed.
Known history of serious hypersensitivity reaction to a known ingredient of pembrolizumab or nivolumab.
Cohort 4B Only: Subjects has microsatellite instability-high or mismatch repair deficient tumors.
Cohort 5 Only, subject has either of the following:
Subject cannot undergo curative resection per the investigator's judgment
Subject meets the following criterion of locoregional disease by clinical TNM staging: cT1N0.

Trial locations and contacts

21 sites in 6 countries.

Country

City, postcode or hospital

21 sites in 6 countries

United States6 sites

Mass General / North Shore Can
Boston, Massachusetts, 02114
University of Chicago
Chicago, Illinois, 60637
The Angeles Clinic and Research Institute
Los Angeles, California, 90025
Memorial Sloan Kettering Cancer Center
New York, New York, 10065
Weill Cornell Medical College
New York, New York, 10065
UCLA Medical Center
Santa Monica, California, 90404

Other trials in United States

France4 sites

Site FR33001
Brest
Site FR33004
Paris, 75015
Site FR33003
Pessac, New Aquitaine, 33604
Site FR33002
Poitiers, New Aquitaine, 86021

Other trials in France

Italy4 sites

Site IT39005
Milan
Site IT39002
Naples
Site IT39004
Padova
Site IT39003
Pisa

Other trials in Italy

Japan3 sites

Site JP81001
Chiba
Site JP81002
Tokyo
Site JP81003
Tokyo

Other trials in Japan

South Korea2 sites

Site KR82002
Seongnam-si
Site KR82001
Seoul

Other trials in South Korea

Taiwan2 sites

Site TW88601
Taichung
Site TW88602
Tainan, 70403

Other trials in Taiwan

About this study

Official title: A Phase 2 Study of Zolbetuximab (IMAB362) as Monotherapy and in Combination With Chemotherapy and/or Immunotherapy in Subjects With Metastatic or Locally Advanced Unresectable Gastric or Gastroesophageal Junction (GEJ) Adenocarcinoma and Locoregional Gastric or GEJ Adenocarcinoma Whose Are Claudin (CLDN) 18.2 Positive

There is an unmet medical need to treat people with advanced cancer in and around the stomach or gastroesophageal junction cancer. This study will provide more information on zolbetuximab given by itself and in combination with other treatments in adults with advanced stomach or gastroesophageal junction cancer. The study is currently ongoing globally. People in this study will either be treated with zolbetuximab by itself, with zolbetuximab and chemotherapy, with zolbetuximab and a medicine called pembrolizumab, or zolbetuximab with chemotherapy and a medicine called nivolumab.

This study is ongoing, but enrollment in any of the treatment options has been completed. In addition, at this stage of the study, treatment in some of these treatment options has completed.

The main aim of this study is to check how well zolbetuximab controls tumors when given by itself.

Adults with cancer in and around the stomach or gastroesophageal junction cancer can take part. Their cancer is locally advanced unresectable or metastatic and has the CLDN18.2 marker in a tumor sample. Locally advanced means the cancer has spread to nearby tissue. Unresectable means the cancer cannot be removed by surgery.

Metastatic means the cancer has spread to other parts of the body. They may have been previously treated with standard therapies. People cannot take part if they need to take medicines to suppress their immune system, have blockages or bleeding in their gut, have specific uncontrollable cancers such as symptomatic or untreated cancers in the nervous system, have a specific heart condition or infections.

There are different treatments in the study. People who take part will receive just 1 of the treatments.

Treatment will be given in cycles. The treatment is given through a vein; this is called an infusion. Some people with advanced disease will have 1 infusion in 3 week (21-day) cycles. Some people will have several infusions in 6 week (42-day) cycles. Some people with cancer in and around the stomach or gastroesophageal junction who have surgery for their cancer will have a few infusions in 2-week (14-day) cycles. This will happen before and after they have surgery for their cancer.

People may receive chemotherapy for up to 6 months. Some people enrolled to received zolbetuximab and pembrolizumab, may have received pembrolizumab for up to 2 years.

People will visit the clinic on certain days during their treatment; there may be extra visits during the first cycle of treatment. The study doctors will check if people had any medical problems from zolbetuximab and the other study treatments. Also, people in the study will have a health check including blood tests. On some visits they will also have scans to check for any changes in their cancer. Tumor samples will be taken at certain visits with the option of giving a tumor sample after treatment has finished.

People will visit the clinic after they stop treatment. They will be asked about any medical problems and will have a health check including blood tests. After the clinic visits end some people will have a telephone health check every 3 months. The number of visits and checks done at each visit will depend on the health of each person and whether they completed their treatment or not.

Read the detailed description

This is a study to assess the antitumor activity of zolbetuximab, an Immunoglobulin (IgG1) chimeric monoclonal antibody directed against CLDN18.2, in subjects with recurrent locally advanced or metastatic gastric or gastroesophageal junction adenocarcinoma and locoregional gastric or GEJ adenocarcinoma whose tumors are CLDN18.2 positive. For each cohort, the study consists of the following periods: pre-screening; screening; treatment; and follow-up for disease progression (or post-treatment follow-up for disease recurrence, which will be conducted for Cohort 5). In addition, there will be a survival follow-up period for Cohorts 1A, 4B, and 5 participants only. Tolerability of zolbetuximab in combination with pembrolizumab in Japanese participant(s) will be evaluated in Cohort 3A DLT assessment. Tolerability of zolbetuximab in combination with mFOLFOX6 and nivolumab in Japanese subject(s) will be evaluated in Cohort 4B, if Japanese subjects are not enrolled in the Cohort 4A DLT assessment.

Conditions: Pharmacokinetics of Zolbetuximab, Gastric Cancer, Gastro-esophageal Junction (GEJ) Cancer, Pharmacokinetics of Oxaliplatin, Pharmacokinetics of Fluorouracil Bolus (5-FU)
Being tested: zolbetuximab, oxaliplatin, leucovorin, fluorouracil, Pembrolizumab
Keywords: zolbetuximab, oxaliplatin, fluorouracil, docetaxel, claudiximab, IMAB362, Gastro-Esophageal Junction cancer, locoregional gastric cancer, Pembrolizumab, Gastric cancer
Medical subject headings: Stomach Neoplasms, Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

zolbetuximabDrug
Also called IMAB362
Zolbetuximab will be administered as a minimum 2-hour IV infusion.
oxaliplatinDrug
Oxaliplatin will be administered as a 2-hour IV infusion.
leucovorinDrug
Leucovorin will be administered as a 2-hour IV infusion.
fluorouracilDrug
Fluorouracil will be administered as IV bolus over 5 to 15 minutes and continuous IV infusion over 46 to 48 hours or per institutional guidelines.
PembrolizumabDrug
Pembrolizumab will be administered intravenously over 30 minutes.
folinic acidDrug
Folnic acid will be administered as a 2-hour IV infusion.
nivolumabDrug
Nivolumab will be administered intravenously according to institutional standards.
DocetaxelDrug
Docetaxel will be administered as a 1-hour IV infusion.

Study groups in NCT03505320
Study group	Role	What they receive
zolbetuximab (Cohort 1A)	Experimental	Participants will be treated with zolbetuximab on a 21-day cycle in which zolbetuximab will be administered as a single agent every 3 weeks until disease progression, toxicity requiring cessation, start of another anti-cancer treatment or other treatment discontinuation criteria are met. Receives: Drug: zolbetuximab
mFOLFOX6 plus zolbetuximab (Cohort 2)	Experimental	Participants will be treated with zolbetuximab and mFOLFOX6 on a 42-day cycle in which zolbetuximab is administered on days 1 and 22, and mFOLFOX6 is administered on days 1, 15 and 29; however, for the first cycle, zolbetuximab will be administered on day 3 (instead of day 1) to allow for pharmacokinetic collection. Participants will receive up to 12 mFOLFOX6 treatments (4 cycles). Beginning at cycle 5, participants may continue on 5-FU and leucovorin or folinic acid along with zolbetuximab for the remainder of the study per investigator's discretion. mFOLFOX6 treatment includes oxaliplatin: intravenous [IV] infusion, leucovorin: IV infusion, fluorouracil bolus: IV bolus, fluorouracil infusion: continuous IV infusion. Receives: Drug: zolbetuximab; Drug: oxaliplatin; Drug: leucovorin; Drug: fluorouracil; Drug: folinic acid
Pembrolizumab plus zolbetuximab (Cohort 3A)	Experimental	Participants will be treated with zolbetuximab and pembrolizumab on a 21-day cycle. Loading dose of zolbetuximab will be administered at cycle 1, day 1 followed by maintenance dose of zolbetuximab once every 3 weeks (Q3W). Pembrolizumab will be administered to 3 to 6 subjects at a intravenously on day 1 of every 21-day cycle and will be infused 1 hour after the zolbetuximab infusion is completed. Tolerability and safety of zolbetuximab in combination with pembrolizumab will be evaluated during the 3-week dose-limiting toxicity (DLT) assessment period. If this cycle 1 dose is not tolerable, a lower dose of zolbetuximab in combination with pembrolizumab will subsequently be evaluated. Receives: Drug: zolbetuximab; Drug: Pembrolizumab
Zolbetuximab in combination with mFOLFOX6 and nivolumab (Cohort 4A/4B)	Experimental	Participants will be treated with zolbetuximab and mFOLFOX6, nivolumab on a 42-day cycle. Cohort 4A: Loading dose of zolbetuximab in combination with nivolumab and mFOLFOX6 on cycle 1 day 1, followed by zolbetuximab in combination with nivolumab and mFOLFOX6 q2w [days 15 and 29] (1 cycle = 6 weeks). Tolerability and safety of zolbetuximab in combination with nivolumab, mFOLFOX6 will be evaluated during the 3-week DLT assessment period. If cycle 1 dose is not tolerable, a lower dose of dose zolbetuximab in combination with nivolumab and mFOLFOX6 will be subsequently evaluated. Cohort 4B: Subjects will be treated with the combination of zolbetuximab, mFOLFOX6 and nivolumab at the dose deemed tolerable in Cohort 4A. Subjects will receive up to 12 mFOLFOX6 treatments (4 cycles). For Cohorts 4A and 4B, beginning at cycle 5, subjects may continue on 5-FU and leucovorin or folinic acid along with zolbetuximab and nivolumab for the remainder of the study per investigator's discretion. Receives: Drug: zolbetuximab; Drug: oxaliplatin; Drug: leucovorin; Drug: fluorouracil; Drug: folinic acid; Drug: nivolumab
Zolbetuximab in combination with FLOT (Cohort 5)	Experimental	Participants will be treated with zolbetuximab \& FLOT for a total of eight 2-week cycles. 4 cycles preoperatively \& 4 cycles postoperatively 6-12 weeks after surgery. Preoperative: Participants will receive zolbetuximab loading dose on cycle 1 day 1, followed by FLOT on cycle 1 day 2. For cycles 2-4, participants may receive zolbetuximab maintenance dose in combination with FLOT, dosed on day 1 of each cycle. However, dosing may be split over 2 days with zolbetuximab administration on day 1 \& FLOT on day 2. Post operative: Participants will receive zolbetuximab loading dose on cycle 5 day 1, followed by FLOT on cycle 5 day 2. For cycles 6-8, participants may receive zolbetuximab maintenance dose in combination with FLOT, dosed on day 1 of each cycle. However, dosing may be split over 2 days with zolbetuximab administration on day 1 and FLOT on day 2. For participants who experience a DLT during preoperative treatment on the loading dose, the postoperative loading dose may be lowered. Receives: Drug: zolbetuximab; Drug: oxaliplatin; Drug: leucovorin; Drug: fluorouracil; Drug: folinic acid; Drug: Docetaxel

What is being measured

The primary outcome is the main question the study is designed to answer.

Objective Response Rate (ORR) of zolbetuximab as a single agent by central review (Cohort 1)
The ORR is defined as the proportion of participants with complete or partial objective response based on Response Evaluation Criteria in Solid Tumors (RECIST) V1.1 (assessed by an independent review committee (IRC)).
Measured: Up to 3 months

Secondary outcomes (73)

Pharmacokinetics (PK) of zolbetuximab: Area Under the Concentration-time Curve from the Time of Dosing Extrapolated to Time Infinity (AUCinf) (Cohorts 1A, 2, 3A, 4 and 5)
AUCinf will be derived from the PK serum samples collected.
Measured: Up to 16 months
PK of zolbetuximab: Area Under the Concentration-time Curve from the Time of Dosing Extrapolated to Time Infinity Percentage (AUCinf (%extrap)) (Cohorts 1A, 2, 3A, 4 and 5)
AUCinf (%extrap) will be derived from the PK serum samples collected.
Measured: Up to 16 months
PK of zolbetuximab: Area Under the Concentration-time Curve from the Time of Dosing Until the Last Measurable Concentration (AUClast) (Cohorts 1A, 2, 3A, 4 and 5)
AUClast will be derived from the PK serum samples collected.
Measured: Up to 16 months
PK of zolbetuximab: Area Under the Concentration-Time Curve from the Time of Dosing to the Start of the Next Dosing Interval (AUCtau) (Cohorts 1A, 2, 3A, 4 and 5)
AUCtau will be derived from the PK serum samples collected.
Measured: Up to 16 months
PK of zolbetuximab: Maximum Concentration (Cmax) (Cohorts 1A, 2, 3A, 4 and 5)
Cmax will be derived from the PK serum samples collected.
Measured: Up to 16 months
PK of zolbetuximab: Concentration Immediately Prior to Dosing (Ctrough) (Cohorts 1A, 2, 3A, 4 and 5)
Ctrough will be derived from the PK serum samples collected.
Measured: Up to 16 months
PK of zolbetuximab: Time of Maximum Concentration (Tmax) (Cohorts 1A, 2, 3A, 4 and 5)
Tmax will be derived from the PK serum samples collected.
Measured: Up to 16 months
PK of zolbetuximab: Terminal Elimination Half-life (T1/2) (Cohorts 1A, 2, 3A, 4 and 5)
T1/2 will be derived from the PK serum samples collected.
Measured: Up to 16 months
PK of zolbetuximab: Time of the last measurable concentration (Tlast) (Cohorts 1A, 2, 3A, 4 and 5)
Tlast will be derived from the PK serum samples collected.
Measured: Up to 16 months
PK of zolbetuximab: Clearance (CL) (Cohorts 1A, 2, 3A, 4 and 5)
CL will be derived from the PK serum samples collected.
Measured: Up to 16 months
PK of zolbetuximab: Volume of Distribution During the Terminal Phase (Vz) (Cohorts 1A, 2, 3A, 4 and 5)
Vz will be derived from the PK serum samples collected.
Measured: Up to 16 months
PK of oxaliplatin: AUCinf (Cohort 2)
AUCinf will be derived from the PK plasma samples collected.
Measured: Up to 16 months
PK of oxaliplatin: AUCinf (%extrap) (Cohort 2)
AUCinf (%extrap) will be derived from the PK plasma samples collected.
Measured: Up to 16 months
PK of oxaliplatin: AUClast (Cohort 2)
AUClast will be derived from the PK plasma samples collected.
Measured: Up to 16 months
PK of oxaliplatin: Cmax (Cohort 2)
Cmax will be derived from the PK plasma samples collected.
Measured: Up to 16 months
PK of oxaliplatin: Tmax (Cohort 2)
Tmax will be derived from the PK plasma samples collected.
Measured: Up to 16 months
PK of oxaliplatin: T1/2 (Cohort 2)
T1/2 will be derived from the PK plasma samples collected.
Measured: Up to 16 months
PK of oxaliplatin: Tlast (Cohort 2)
Tlast will be derived from the PK plasma samples collected.
Measured: Up to 16 months
PK of oxaliplatin: CL (Cohort 2)
TL will be derived from the PK plasma samples collected.
Measured: Up to 16 months
PK of oxaliplatin: Vz (Cohort 2)
Vz will be derived from the PK plasma samples collected.
Measured: Up to 16 months
PK of fluorouracil bolus (5-FU): AUCinf (Cohort 2)
AUCinf will be derived from the PK plasma samples collected.
Measured: Up to 16 months
PK of fluorouracil bolus (5-FU): AUCinf (%extrap) (Cohort 2)
AUCinf (%extrap) will be derived from the PK plasma samples collected.
Measured: Up to 16 months
PK of fluorouracil bolus (5-FU): AUClast (Cohort 2)
AUClast will be derived from the PK plasma samples collected.
Measured: Up to 16 months
PK of fluorouracil bolus (5-FU): Cmax (Cohort 2)
Cmax will be derived from the PK plasma samples collected.
Measured: Up to 16 months
PK of fluorouracil bolus (5-FU): Tmax (Cohort 2)
Tmax will be derived from the PK plasma samples collected.
Measured: Up to 16 months
PK of fluorouracil bolus (5-FU): T1/2 (Cohort 2)
T1/2 will be derived from the PK plasma samples collected.
Measured: Up to 16 months
PK of fluorouracil bolus (5-FU): Tlast (Cohort 2)
Tlast will be derived from the PK plasma samples collected.
Measured: Up to 16 months
PK of fluorouracil bolus (5-FU): CL (Cohort 2)
CL will be derived from the PK plasma samples collected.
Measured: Up to 16 months
PK of fluorouracil bolus (5-FU): Vz (Cohort 2)
Vz will be derived from the PK plasma samples collected.
Measured: Up to 16 months
Safety and tolerability assessed by adverse events (AEs) (Cohorts 1A, 2, 3A, 4 and 5)
An AE is any untoward medical occurrence in a participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.
Measured: Up to 16 months
Number of participants with electrocardiogram (ECG) abnormalities and or adverse events (Cohorts 1A, 2, 3A, 4 and 5)
Number of participants with potentially clinically significant ECG values.
Measured: Up to 14 months
Number of participants with vital signs abnormalities and or adverse events (Cohorts 1A, 2, 3A, 4 and 5)
Number of participants with potentially clinically significant vital sign values.
Measured: Up to 14 months
Number of participants with European Cooperative Oncology Group (ECOG) performance status abnormalities and or adverse events (Cohorts 1A, 2, 3A, 4 and 5)
Number of participants with potentially clinically significant ECOG performance status values. ECOG grades 0-5, where 0 = Fully active, able to carry on all pre-disease performance without restriction; 1 = Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, e.g., light house work, office work; 2 = Ambulatory and capable of all self-care but unable to carry out any work activities. Up and about more than 50% of waking hours; 3 = Capable of only limited self-care, confined to bed or chair more than 50% of waking hours; 4 = Completely disabled. Cannot carry on any self-care. Totally confined to bed or chair and 5 = Dead.
Measured: Up to 14 months
Number of participants with laboratory assessments abnormalities and or adverse events (Cohorts 1A, 2, 3A, 4 and 5)
Number of participants with potentially clinically significant laboratory values.
Measured: Up to 14 months
Number of anti-drug antibody (ADA) Positive Participants (Cohorts 1A, 2, 3A, 4 and 5)
Immunogenicity will be measured by the number of participants that are ADA positive.
Measured: Up to 16 months
Health Related Quality of Life (HRQoL) measured by the Quality of Life Questionnaire - Core Questionnaire (QLQ-C30) questionnaire (Cohorts 1A, 2, 3A, 4 and 5)
The EORTC-QLQ-C30 is a cancer-specific instrument consisting of 5 functional domain scales: physical, role, emotional, social and cognitive.
Measured: Up to 16 months
HRQoL measured by the Oesophago-Gastric Module (EORTC QLQ-OG-25) questionnaire (Cohorts 1A, 2, 3A, 4 and 5)
The EORTC-QLQ-OG25 instrument evaluates GC- and GEJC-specific symptoms such as stomach discomfort, difficulties eating and swallowing and indigestion.
Measured: Up to 16 months
HRQoL measured by the Global Pain (GP) questionnaire (Cohorts 1A, 2, 3A, 4 and 5)
The GP instrument is a single assessment of overall pain.
Measured: Up to 16 months
HRQoL measured by the EuroQOL Five Dimensions Questionnaire 5L (EQ-5D-5L) questionnaire (Cohorts 1A, 2, 3A, 4 and 5)
The EQ-5D-5L is a standardized instrument developed by the EuroQol Group for use as a generic, preference-based measure of health outcomes. The EQ-5D-5L is a 5-item self-reported measure of functioning and wellbeing, which assesses 5 dimensions of health, including mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension comprises 5 levels (no problems, slight problems, moderate problems, severe problems, extreme problems). A unique EQ-5D-5L health state is defined by combining 1 level from each of the 5 dimensions. This questionnaire also records the respondent's self-rated health status on a vertical graduated (0 = the worst health a participant can imagine to 100 = the best health a participant can imagine) visual analogue scale. Responses to the 5 items will also be converted to a weighted health state index (utility score) based on values derived from general population samples.
Measured: Up to 16 months
HRQoL measured by the Health Resource Utilization (HRU) questionnaire (Cohorts 1A, 2, 3A, 4 and 5)
Health resource utilization questionnaire to assess the number of office visits, hospital stays and other healthcare resource utilization that occur outside of the clinical trial.
Measured: Up to 16 months
Disease Control Rate (DCR) of zolbetuximab as a single agent by investigator assessment (Cohort 1A)
The DCR is defined as the proportion of subjects with complete or partial objective response, or stable disease based on RECIST V1.1.
Measured: Up to 3 months
DCR of zolbetuximab in combination with mFOLFOX6 by investigator assessment (Cohort 2)
The DCR is defined as the proportion of subjects with complete or partial objective response, or stable disease based on RECIST V1.1.
Measured: Up to 13 months
DCR of zolbetuximab in combination with mFOLFOX6 (with nivolumab) by investigator assessment (Cohort 4)
DCR is defined as the proportion of subjects with complete or partial objective response, or stable disease based on RECIST V1.1.
Measured: up to 13 months
DCR of zolbetuximab as a single agent by independent central reader (Cohort 1A)
The DCR is defined as the proportion of subjects with complete or partial objective response, or stable disease based on RECIST V1.1.
Measured: Up to 3 months
DCR of zolbetuximab in combination with mFOLFOX6 by Independent central reader (Cohort 2)
The DCR is defined as the proportion of subjects with complete or partial objective response, or stable disease based on RECIST V1.1.
Measured: Up to 13 months
Duration of Response (DOR) of zolbetuximab as a single agent by investigator assessment (Cohort 1A)
DOR is defined as the time from the date of the first response CR/PR (whichever is first recorded) to the date of radiographical progression/death or date of censoring.
Measured: Up to 3 months
DOR of zolbetuximab in combination with mFOLFOX6 by investigator assessment (Cohort 2)
DOR is defined as the time from the date of the first response CR/PR (whichever is first recorded) to the date of radiographical progression/death or date of censoring.
Measured: Up to 13 months
DOR of zolbetuximab in combination with mFOLFOX6 (with nivolumab) by investigator assessment (Cohort 4)
DOR is defined as the time from the date of the first response CR/PR (whichever is first recorded) to the date of radiographical progression/death or date of censoring.
Measured: up to 13 months
DOR of zolbetuximab as a single agent by independent central reader (Cohort 1A)
DOR is defined as the time from the date of the first response CR/PR (whichever is first recorded) to the date of radiographical progression/death or date of censoring.
Measured: Up to 3 months
DOR of zolbetuximab in combination with mFOLFOX6 by independent central reader (Cohort 2)
DOR is defined as the time from the date of the first response CR/PR (whichever is first recorded) to the date of radiographical progression/death or date of censoring.
Measured: Up to 13 months
Progression Free Survival (PFS) of zolbetuximab as a single agent by investigator assessment (Cohort 1A)
PFS is defined as the time from date of treatment start until the date of radiological disease progression assessed by independent radiographic reviewer (IRR), or until death due to any cause.
Measured: Up to 3 months
PFS of zolbetuximab in combination with mFOLFOX6 by investigator assessment (Cohort 2)
PFS is defined as the time from date of treatment start until the date of radiological disease progression assessed by independent radiographic reviewer (IRR), or until death due to any cause.
Measured: Up to 13 months
PFS of zolbetuximab in combination with mFOLFOX6 (with nivolumab) by investigator assessment (Cohort 4)
PFS is defined as the time from date of treatment start until the date of radiological disease progression assessed by independent radiographic reviewer (IRR), or until death due to any cause.
Measured: up to 13 months
PFS of zolbetuximab as a single agent by independent central review (Cohort 1A)
PFS is defined as the time from date of treatment start until the date of radiological disease progression assessed by independent radiographic reviewer (IRR), or until death due to any cause.
Measured: Up to 3 months
PFS of zolbetuximab in combination with mFOLFOX6 by independent central review (Cohort 2)
PFS is defined as the time from date of treatment start until the date of radiological disease progression assessed by independent radiographic reviewer (IRR), or until death due to any cause.
Measured: Up to 13 months
ORR of zolbetuximab as a single agent by investigator assessment (Cohort 1A)
The ORR is defined as the proportion of subjects with complete or partial objective response based on RECIST V1.1.
Measured: Up to 3 months
ORR of zolbetuximab in combination with mFOLFOX6 by investigator assessment (Cohort 2)
The ORR is defined as the proportion of subjects with complete or partial objective response based on RECIST V1.1.
Measured: Up to 13 months
ORR of zolbetuximab in combination with mFOLFOX6 (with nivolumab) by investigator assessment (Cohort 4)
The ORR is defined as the proportion of subjects with complete or partial objective response based on RECIST V1.1.
Measured: up to 13 months
ORR of zolbetuximab in combination with mFOLFOX6 by independent central reader (Cohort 2)
The ORR is defined as the proportion of subjects with complete or partial objective response based on RECIST V1.1.
Measured: Up to 13 months
ORR of zolbetuximab in combination with pembrolizumab by independent central reader (Cohort 3A)
The ORR is defined as the proportion of subjects with complete or partial objective response based on RECIST V1.1.
Measured: Up to 5 months
Overall Survival (OS) of zolbetuximab as a single agent (Cohort 1A)
OS is defined as the time from the date of treatment start until the documented date of death from any cause.
Measured: Up to 7 months
OS of zolbetuximab in combination with mFOLFOX6 and nivolumab (Cohort 4B)
OS is defined as the time from the date of treatment start until the documented date of death from any cause.
Measured: up to 56 Months
OS of zolbetuximab in combination with FLOT (Cohort 5)
OS is defined as the time from the date of treatment start until the documented date of death from any cause.
Measured: Up to 72 months
Percentage of participants with surgical complications (Cohort 5)
Percentage of participants with surgical complications will be reported.
Measured: Up to 8 months
Percentage of participants with surgical mortality as defined by death within 30 days of surgery (Cohort 5)
Percentage of participants with surgical mortality as defined by death within 30 days of surgery will be reported.
Measured: Up to 30 days
Percentage of participants able to complete preoperative chemotherapy (Cohort 5)
Percentage of participants able to complete preoperative chemotherapy will be reported.
Measured: Up to 2 months
Percentage of participants with perioperative mortality and morbidity at 30 days and 90 days post last dose (Cohort 5)
Percentage of participants with perioperative mortality and morbidity at 30 days and 90 days post last dose will be reported.
Measured: Up to 3 months
Percentage of participants able to start postoperative chemotherapy (Cohort 5)
Percentage of participants able to start postoperative chemotherapy will be reported.
Measured: Up to 7 months
Percentage of participants able to complete postoperative chemotherapy (Cohort 5)
Percentage of participants able to complete postoperative chemotherapy will be reported.
Measured: Up to 9 months
Percentage of participants with radiological response at restaging (Cohort 5)
Radiological response will include complete response and partial response.
Measured: Up to 5 months
Percentage of subjects with pathological response (ypTNM) (Cohort 5)
Pathological response (ypTNM) will include ypCR, ypPR
Measured: Up to 5 months
Disease-free Survival (DFS) (Cohort 5)
DFS is defined as the time from date of treatment start until the date of radiological disease recurrence or until death due to any cause, whichever is earliest.
Measured: Up to 70 months
Minimal Residual Disease (Cohort 5)
Minimal residual disease and disease recurrence as measured by circulating tumor DNA (ctDNA) will be summarized.
Measured: Up to 37 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

29 Jun 201831 May 2028

First posted23 Apr 2018
Study start29 Jun 2018
Primary completion30 Jun 2027 (estimated)
Study completion31 May 2028 (estimated)

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Publications (2)Papers the sponsor has linked to this study.
Other trials for Pharmacokinetics of ZolbetuximabStudies of the same condition, open and under way.
More trials run by Astellas Pharma Global Development, Inc.The sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2
Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Parallel groups
Masking: Double blind
Who is masked: Participant, Investigator
Enrolment: 143 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03505320
Sponsor's protocol ID: 8951-CL-0103
Other IDs: 2017-002566-50, jRCT2080225325, 2024-511649-21-00, 2017
Acronym: ILUSTRO
Status last verified: Aug 2026
First submitted: 29 Mar 2018
Last updated: 31 Aug 2026
Results posted: No
Data monitoring committee: No
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: Yes: Access to anonymized individual participant level data collected during the study, in addition to study-related supporting documentation, is planned for studies conducted with approved product indications and formulations, as well as products terminated during development. Studies conducted with product indications or formulations that remain active in development are assessed after study completion to determine if Individual Participant Data can be shared. Further details on Astellas' data sharing policy can be found at https://www.clinicaltrials.astellas.com/transparency/.
Expanded access: Available

Publications

Shitara K, Shoji H, Fazio N, Lonardi S, Lee KW, Bai LY, Yamaguchi K, Metges JP, Masi G, Smith D, Kim TY, Matsangou M, Shrivastava A, Zhou M, Hill J, Guerrero A, Wang X, Zaanan A, Klempner SJ. First-line zolbetuximab plus mFOLFOX6 and nivolumab in unresectable CLDN18.2-positive gastric or gastroesophageal junction adenocarcinoma: a phase 2 trial. Nat Med. 2026 Jun;32(6):2182-2190. doi: 10.1038/s41591-026-04306-9. Epub 2026 Mar 16.
PubMed 41840238
Yu J, Mehta R. Biomarker-Driven Approach to the Treatment of Metastatic Gastric or Gastroesophageal Adenocarcinoma. J Natl Compr Canc Netw. 2025 May;23(5):e257036. doi: 10.6004/jnccn.2025.7036.
PubMed 40341124

Study at a glance

From the registry record, last updated by the sponsor on 31 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Phase 2 Study of Zolbetuximab (IMAB362) as Monotherapy and in Combination With Chemotherapy and/or Immunotherapy in Subjects With Metastatic or Locally Advanced Unresectable Gastric or Gastroesophageal Junction (GEJ) Adenocarcinoma and Locoregional Gastric or GEJ Adenocarcinoma Whose Are Claudin (CLDN) 18.2 Positive
ClinicalTrials.gov ID: NCT03505320
Acronym / sponsor ID: ILUSTRO / 8951-CL-0103
Conditions: Pharmacokinetics of Zolbetuximab, Gastric Cancer, Gastro-esophageal Junction (GEJ) Cancer, Pharmacokinetics of Oxaliplatin, Pharmacokinetics of Fluorouracil Bolus (5-FU)
Keywords: zolbetuximab, oxaliplatin, fluorouracil, docetaxel, claudiximab, IMAB362, Gastro-Esophageal Junction cancer, locoregional gastric cancer
Phase: Phase 2
Study type: Interventional
Recruitment status: Active, not recruiting
Enrolment: 143 participants (actual)
Lead sponsor: Astellas Pharma Global Development, Inc.Industry (pharma, biotech, devices)
Study start: 29 Jun 2018 (actual)
Primary completion: 30 Jun 2027 (estimated)
Study completion: 31 May 2028 (estimated)
First posted: 23 Apr 2018 (actual)
Results: Not posted in the source record

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

This study is ongoing, but enrollment in any of the treatment options has been completed. In addition, at this stage of the study, treatment in some of these treatment options has completed.

The main aim of this study is to check how well zolbetuximab controls tumors when given by itself.

There are different treatments in the study. People who take part will receive just 1 of the treatments.

People may receive chemotherapy for up to 6 months. Some people enrolled to received zolbetuximab and pembrolizumab, may have received pembrolizumab for up to 2 years.

Detailed description

Study design

Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Parallel groups
Masking: Double blind (participant, investigator)
Number of arms: 5

Arm	Type	Receives
zolbetuximab (Cohort 1A)	Experimental	Drug: zolbetuximabParticipants will be treated with zolbetuximab on a 21-day cycle in which zolbetuximab will be administered as a single agent every 3 weeks until disease progression, toxicity requiring cessation, start of another anti-cancer treatment or other treatment discontinuation criteria are met.
mFOLFOX6 plus zolbetuximab (Cohort 2)	Experimental	Drug: zolbetuximab, Drug: oxaliplatin, Drug: leucovorin, Drug: fluorouracil, Drug: folinic acidParticipants will be treated with zolbetuximab and mFOLFOX6 on a 42-day cycle in which zolbetuximab is administered on days 1 and 22, and mFOLFOX6 is administered on days 1, 15 and 29; however, for the first cycle, zolbetuximab will be administered on day 3 (instead of day 1) to allow for pharmacokinetic collection. Participants will receive up to 12 mFOLFOX6 treatments (4 cycles). Beginning at cycle 5, participants may continue on 5-FU and leucovorin or folinic acid along with zolbetuximab for the remainder of the study per investigator's discretion. mFOLFOX6 treatment includes oxaliplatin: intravenous [IV] infusion, leucovorin: IV infusion, fluorouracil bolus: IV bolus, fluorouracil infusion: continuous IV infusion.
Pembrolizumab plus zolbetuximab (Cohort 3A)	Experimental	Drug: zolbetuximab, Drug: PembrolizumabParticipants will be treated with zolbetuximab and pembrolizumab on a 21-day cycle. Loading dose of zolbetuximab will be administered at cycle 1, day 1 followed by maintenance dose of zolbetuximab once every 3 weeks (Q3W). Pembrolizumab will be administered to 3 to 6 subjects at a intravenously on day 1 of every 21-day cycle and will be infused 1 hour after the zolbetuximab infusion is completed. Tolerability and safety of zolbetuximab in combination with pembrolizumab will be evaluated during the 3-week dose-limiting toxicity (DLT) assessment period. If this cycle 1 dose is not tolerable, a lower dose of zolbetuximab in combination with pembrolizumab will subsequently be evaluated.
Zolbetuximab in combination with mFOLFOX6 and nivolumab (Cohort 4A/4B)	Experimental	Drug: zolbetuximab, Drug: oxaliplatin, Drug: leucovorin, Drug: fluorouracil, Drug: folinic acid, Drug: nivolumabParticipants will be treated with zolbetuximab and mFOLFOX6, nivolumab on a 42-day cycle. Cohort 4A: Loading dose of zolbetuximab in combination with nivolumab and mFOLFOX6 on cycle 1 day 1, followed by zolbetuximab in combination with nivolumab and mFOLFOX6 q2w [days 15 and 29] (1 cycle = 6 weeks). Tolerability and safety of zolbetuximab in combination with nivolumab, mFOLFOX6 will be evaluated during the 3-week DLT assessment period. If cycle 1 dose is not tolerable, a lower dose of dose zolbetuximab in combination with nivolumab and mFOLFOX6 will be subsequently evaluated. Cohort 4B: Subjects will be treated with the combination of zolbetuximab, mFOLFOX6 and nivolumab at the dose deemed tolerable in Cohort 4A. Subjects will receive up to 12 mFOLFOX6 treatments (4 cycles). For Cohorts 4A and 4B, beginning at cycle 5, subjects may continue on 5-FU and leucovorin or folinic acid along with zolbetuximab and nivolumab for the remainder of the study per investigator's discretion.
Zolbetuximab in combination with FLOT (Cohort 5)	Experimental	Drug: zolbetuximab, Drug: oxaliplatin, Drug: leucovorin, Drug: fluorouracil, Drug: folinic acid, Drug: DocetaxelParticipants will be treated with zolbetuximab \& FLOT for a total of eight 2-week cycles. 4 cycles preoperatively \& 4 cycles postoperatively 6-12 weeks after surgery. Preoperative: Participants will receive zolbetuximab loading dose on cycle 1 day 1, followed by FLOT on cycle 1 day 2. For cycles 2-4, participants may receive zolbetuximab maintenance dose in combination with FLOT, dosed on day 1 of each cycle. However, dosing may be split over 2 days with zolbetuximab administration on day 1 \& FLOT on day 2. Post operative: Participants will receive zolbetuximab loading dose on cycle 5 day 1, followed by FLOT on cycle 5 day 2. For cycles 6-8, participants may receive zolbetuximab maintenance dose in combination with FLOT, dosed on day 1 of each cycle. However, dosing may be split over 2 days with zolbetuximab administration on day 1 and FLOT on day 2. For participants who experience a DLT during preoperative treatment on the loading dose, the postoperative loading dose may be lowered.

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (54 listed)

Female subject eligible to participate if she is not pregnant and at least one of the following conditions applies:
Female subject must agree not to breastfeed starting at screening and throughout the study period, and for 6 months after the final study drug administration.
Female subject must agree not to donate ova starting at screening and throughout the study period, and for 9 months after the final oxaliplatin administration and 6 months after the final administration of all other study drugs.
A sexually active male subject with a female partner(s) who is of child-bearing potential must agree to use contraception during the treatment period and for at least 6 months after the final study drug administration.
Male subject must agree not to donate sperm starting at screening and throughout the study period, and for 6 months after the final study drug administration.

Key exclusion criteria (34 listed)

Subject has had prior severe allergic reaction or intolerance to known ingredients of zolbetuximab or other monoclonal antibodies, including humanized or chimeric antibodies.
Subject has known immediate or delayed hypersensitivity or contraindication to any component of study treatment.
Subject has received other investigational agents or devices concurrently or within 28 days prior to first dose of study treatment.
Subject has received systemic immunosuppressive therapy, including systemic corticosteroids 14 days prior to first dose of study treatment.
Subject has a complete gastric outlet syndrome or a partial gastric outlet syndrome with persistent recurrent vomiting.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
zolbetuximabAlso: IMAB362Zolbetuximab will be administered as a minimum 2-hour IV infusion.	Drug	Pembrolizumab plus zolbetuximab (Cohort 3A), Zolbetuximab in combination with FLOT (Cohort 5), Zolbetuximab in combination with mFOLFOX6 and nivolumab (Cohort 4A/4B), mFOLFOX6 plus zolbetuximab (Cohort 2), zolbetuximab (Cohort 1A)
oxaliplatinOxaliplatin will be administered as a 2-hour IV infusion.	Drug	Zolbetuximab in combination with FLOT (Cohort 5), Zolbetuximab in combination with mFOLFOX6 and nivolumab (Cohort 4A/4B), mFOLFOX6 plus zolbetuximab (Cohort 2)
leucovorinLeucovorin will be administered as a 2-hour IV infusion.	Drug	Zolbetuximab in combination with FLOT (Cohort 5), Zolbetuximab in combination with mFOLFOX6 and nivolumab (Cohort 4A/4B), mFOLFOX6 plus zolbetuximab (Cohort 2)
fluorouracilFluorouracil will be administered as IV bolus over 5 to 15 minutes and continuous IV infusion over 46 to 48 hours or per institutional guidelines.	Drug	Zolbetuximab in combination with FLOT (Cohort 5), Zolbetuximab in combination with mFOLFOX6 and nivolumab (Cohort 4A/4B), mFOLFOX6 plus zolbetuximab (Cohort 2)
PembrolizumabPembrolizumab will be administered intravenously over 30 minutes.	Drug	Pembrolizumab plus zolbetuximab (Cohort 3A)
folinic acidFolnic acid will be administered as a 2-hour IV infusion.	Drug	Zolbetuximab in combination with FLOT (Cohort 5), Zolbetuximab in combination with mFOLFOX6 and nivolumab (Cohort 4A/4B), mFOLFOX6 plus zolbetuximab (Cohort 2)
nivolumabNivolumab will be administered intravenously according to institutional standards.	Drug	Zolbetuximab in combination with mFOLFOX6 and nivolumab (Cohort 4A/4B)
DocetaxelDocetaxel will be administered as a 1-hour IV infusion.	Drug	Zolbetuximab in combination with FLOT (Cohort 5)

Primary outcome

Objective Response Rate (ORR) of zolbetuximab as a single agent by central review (Cohort 1)
Time frame: Up to 3 months
The ORR is defined as the proportion of participants with complete or partial objective response based on Response Evaluation Criteria in Solid Tumors (RECIST) V1.1 (assessed by an independent review committee (IRC)).

73 secondary outcomes

Pharmacokinetics (PK) of zolbetuximab: Area Under the Concentration-time Curve from the Time of Dosing Extrapolated to Time Infinity (AUCinf) (Cohorts 1A, 2, 3A, 4 and 5)
Time frame: Up to 16 months
PK of zolbetuximab: Area Under the Concentration-time Curve from the Time of Dosing Extrapolated to Time Infinity Percentage (AUCinf (%extrap)) (Cohorts 1A, 2, 3A, 4 and 5)
Time frame: Up to 16 months
PK of zolbetuximab: Area Under the Concentration-time Curve from the Time of Dosing Until the Last Measurable Concentration (AUClast) (Cohorts 1A, 2, 3A, 4 and 5)
Time frame: Up to 16 months
PK of zolbetuximab: Area Under the Concentration-Time Curve from the Time of Dosing to the Start of the Next Dosing Interval (AUCtau) (Cohorts 1A, 2, 3A, 4 and 5)
Time frame: Up to 16 months
PK of zolbetuximab: Maximum Concentration (Cmax) (Cohorts 1A, 2, 3A, 4 and 5)
Time frame: Up to 16 months
PK of zolbetuximab: Concentration Immediately Prior to Dosing (Ctrough) (Cohorts 1A, 2, 3A, 4 and 5)
Time frame: Up to 16 months
PK of zolbetuximab: Time of Maximum Concentration (Tmax) (Cohorts 1A, 2, 3A, 4 and 5)
Time frame: Up to 16 months
PK of zolbetuximab: Terminal Elimination Half-life (T1/2) (Cohorts 1A, 2, 3A, 4 and 5)
Time frame: Up to 16 months
PK of zolbetuximab: Time of the last measurable concentration (Tlast) (Cohorts 1A, 2, 3A, 4 and 5)
Time frame: Up to 16 months
PK of zolbetuximab: Clearance (CL) (Cohorts 1A, 2, 3A, 4 and 5)
Time frame: Up to 16 months
PK of zolbetuximab: Volume of Distribution During the Terminal Phase (Vz) (Cohorts 1A, 2, 3A, 4 and 5)
Time frame: Up to 16 months
PK of oxaliplatin: AUCinf (Cohort 2)
Time frame: Up to 16 months
PK of oxaliplatin: AUCinf (%extrap) (Cohort 2)
Time frame: Up to 16 months
PK of oxaliplatin: AUClast (Cohort 2)
Time frame: Up to 16 months
PK of oxaliplatin: Cmax (Cohort 2)
Time frame: Up to 16 months
PK of oxaliplatin: Tmax (Cohort 2)
Time frame: Up to 16 months
PK of oxaliplatin: T1/2 (Cohort 2)
Time frame: Up to 16 months
PK of oxaliplatin: Tlast (Cohort 2)
Time frame: Up to 16 months
PK of oxaliplatin: CL (Cohort 2)
Time frame: Up to 16 months
PK of oxaliplatin: Vz (Cohort 2)
Time frame: Up to 16 months
PK of fluorouracil bolus (5-FU): AUCinf (Cohort 2)
Time frame: Up to 16 months
PK of fluorouracil bolus (5-FU): AUCinf (%extrap) (Cohort 2)
Time frame: Up to 16 months
PK of fluorouracil bolus (5-FU): AUClast (Cohort 2)
Time frame: Up to 16 months
PK of fluorouracil bolus (5-FU): Cmax (Cohort 2)
Time frame: Up to 16 months
PK of fluorouracil bolus (5-FU): Tmax (Cohort 2)
Time frame: Up to 16 months
PK of fluorouracil bolus (5-FU): T1/2 (Cohort 2)
Time frame: Up to 16 months
PK of fluorouracil bolus (5-FU): Tlast (Cohort 2)
Time frame: Up to 16 months
PK of fluorouracil bolus (5-FU): CL (Cohort 2)
Time frame: Up to 16 months
PK of fluorouracil bolus (5-FU): Vz (Cohort 2)
Time frame: Up to 16 months
Safety and tolerability assessed by adverse events (AEs) (Cohorts 1A, 2, 3A, 4 and 5)
Time frame: Up to 16 months
Number of participants with electrocardiogram (ECG) abnormalities and or adverse events (Cohorts 1A, 2, 3A, 4 and 5)
Time frame: Up to 14 months
Number of participants with vital signs abnormalities and or adverse events (Cohorts 1A, 2, 3A, 4 and 5)
Time frame: Up to 14 months
Number of participants with European Cooperative Oncology Group (ECOG) performance status abnormalities and or adverse events (Cohorts 1A, 2, 3A, 4 and 5)
Time frame: Up to 14 months
Number of participants with laboratory assessments abnormalities and or adverse events (Cohorts 1A, 2, 3A, 4 and 5)
Time frame: Up to 14 months
Number of anti-drug antibody (ADA) Positive Participants (Cohorts 1A, 2, 3A, 4 and 5)
Time frame: Up to 16 months
Health Related Quality of Life (HRQoL) measured by the Quality of Life Questionnaire - Core Questionnaire (QLQ-C30) questionnaire (Cohorts 1A, 2, 3A, 4 and 5)
Time frame: Up to 16 months
HRQoL measured by the Oesophago-Gastric Module (EORTC QLQ-OG-25) questionnaire (Cohorts 1A, 2, 3A, 4 and 5)
Time frame: Up to 16 months
HRQoL measured by the Global Pain (GP) questionnaire (Cohorts 1A, 2, 3A, 4 and 5)
Time frame: Up to 16 months
HRQoL measured by the EuroQOL Five Dimensions Questionnaire 5L (EQ-5D-5L) questionnaire (Cohorts 1A, 2, 3A, 4 and 5)
Time frame: Up to 16 months
HRQoL measured by the Health Resource Utilization (HRU) questionnaire (Cohorts 1A, 2, 3A, 4 and 5)
Time frame: Up to 16 months

Results and safety

This study is still under way. Results are not available in the source record yet.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 31 Aug 2026.
Derived from this study: PubMed 41840238Shitara K, Shoji H, Fazio N, Lonardi S, Lee KW, Bai LY, Yamaguchi K, Metges JP, Masi G, Smith D, Kim TY, Matsangou M, Shrivastava A, Zhou M, Hill J, Guerrero A, Wang X, Zaanan A, Klempner SJ. First-line zolbetuximab plus mFOLFOX6 and nivolumab in unresectable CLDN18.2-positive gastric or gastroesophageal junction adenocarcinoma: a phase 2 trial. Nat Med. 2026 Jun;32(6):2182-2190. doi: 10.1038/s41591-026-04306-9. Epub 2026 Mar 16.
Derived from this study: PubMed 40341124Yu J, Mehta R. Biomarker-Driven Approach to the Treatment of Metastatic Gastric or Gastroesophageal Adenocarcinoma. J Natl Compr Canc Netw. 2025 May;23(5):e257036. doi: 10.6004/jnccn.2025.7036.
Individual participant dataSharing planned: Yes. Access to anonymized individual participant level data collected during the study, in addition to study-related supporting documentation, is planned for studies conducted with approved product indications and formulations, as well as products terminated during development. Studies conducted with product indications or formulations that remain active in development are assessed after study completion to determine if Individual Participant Data can be shared. Further details on Astellas' data sharing policy can be found at https://www.clinicaltrials.astellas.com/transparency/.

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Global Medical Lead study director

Astellas Pharma Global Development, Inc.

21 sites in 6 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 54 inclusion and 34 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 31 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 21 sites in United States, France, Italy, Japan, South Korea and 1 more country. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Objective Response Rate (ORR) of zolbetuximab as a single agent by central review (Cohort 1) (time frame: Up to 3 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03505320, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 31 Aug 2026.