Trials / Active Not Recruiting

Active Not RecruitingNCT03504397

A Study to Compare Zolbetuximab (IMAB362) and Chemotherapy With Placebo and Chemotherapy in Adults With Gastric Cancer.

A Phase 3, Global, Multi-Center, Double-Blind, Randomized, Efficacy Study of Zolbetuximab (IMAB362) Plus mFOLFOX6 Compared With Placebo Plus mFOLFOX6 as First-line Treatment of Subjects With Claudin (CLDN)18.2-Positive, HER2-Negative, Locally Advanced Unresectable or Metastatic Gastric or Gastroesophageal Junction (GEJ) Adenocarcinoma

Status: Active Not Recruiting
Phase: Phase 3
Study type: Interventional
Enrollment: 565 (actual)

Sponsor: Astellas Pharma Global Development, Inc. · Industry
Sex: All
Age: 18 Years
Healthy volunteers: Not accepted

Summary

Zolbetuximab is being studied in people with cancer in and around the stomach or where the food pipe (esophagus) joins the stomach, called gastroesophageal junction (GEJ) cancer. Most people with this type of cancer have a protein called Claudin 18.2 in their tumor. Zolbetuximab is thought to work by attaching to the Claudin 18.2 protein in their tumor, which switches on the body's immune system to attack the tumor. There is an unmet medical need to treat people with advanced stomach cancer or GEJ cancer. This study will give more information about how well zolbetuximab works when given with chemotherapy in adults with advanced stomach cancer or GEJ cancer. In this study, adults with advanced stomach cancer or GEJ cancer will either be given zolbetuximab with chemotherapy or a placebo with chemotherapy. A placebo looks like zolbetuximab but doesn't have any medicine in it. Zolbetuximab with chemotherapy has already been approved to treat gastric cancer and GEJ cancer in some countries. This study is being done in countries where zolbetuximab has not yet been approved for use. If zolbetuximab becomes approved for use in those countries taking part in this study, the study doctor will switch study treatment in those countries to the licensed zolbetuximab. If this happens, people taking part in those countries will leave this study and receive licensed zolbetuximab. The main aim of the study is to check if zolbetuximab and chemotherapy can prevent or delay the worsening of people's gastric cancer and GEJ cancer compared to placebo and chemotherapy. Adults with advanced stomach cancer or GEJ cancer can take part. 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. A tumor sample of their cancer will also have the Claudin 18.2 protein. They may have been previously treated with certain standard therapies, but have not been treated with chemotherapy for their cancer. 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, or have a specific heart condition, or infections. The study treatments are either zolbetuximab with chemotherapy, or placebo with chemotherapy. People who take part will receive just 1 of the study treatments by chance. Study treatment will be double-blinded. That means that the people in the study and the study doctors will not know who takes which of the study treatments. Study treatment will be given in cycles. The study treatment is given to people slowly through a tube into a vein. This is called an infusion. People will have 4 infusions in 6-week (42-day) cycles as follows: * Zolbetuximab or placebo - 2 infusions in a cycle. * Chemotherapy (called modified FOLFOX6 or mFOLFOX6) - 3 infusions in a cycle. The first infusion is combined with zolbetuximab or placebo on day 1 of each cycle. People may receive zolbetuximab or placebo until their cancer worsens, they cannot tolerate the study treatment, or they need to start another cancer treatment. People will receive mFOLFOX6 for up to 6 months (4 study treatment cycles). After the 6 months people may receive chemotherapy containing folinic acid and fluorouracil instead of mFOLFOX6. People may receive folinic acid and fluorouracil chemotherapy for more than 6 months, or until their cancer worsens, they cannot tolerate the study treatment, or they need to start another cancer treatment. People will visit the clinic on certain days during their study treatment. The study doctors will check if people had any medical problems from taking zolbetuximab or the other study treatments. Also, people in the study will have health checks. On some visits they will have scans to check for any changes in their cancer. People will have the option of giving a tumor sample after their study treatment has finished. People will visit the clinic after they stop their study treatment. People who start treatment with licensed zolbetuximab or mFOLFOX6 outside of this study will not need to visit the clinic. People will be asked about any medical problems and will have a health check. People will visit the clinic at 1 month after they stop their study treatment. People will continue to have scans every 9 or 12 weeks to check for any changes in their cancer. People will have telephone health checks 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 study treatment or not.

Detailed description

After the marketing approval in Japan on 26 Mar 2024, this study continued as "post marketing clinical study" in Japan. In the rest of the countries which participated in this study, this study continued as clinical study.

Conditions

Interventions

Type	Name	Description
DRUG	zolbetuximab	Participants received an IV infusion (as a minimum of 2-hour infusion) of zolbetuximab at a loading dose of 800 mg/m\^2 on C1D1 followed by subsequent doses of 600 mg/m\^2 every 3 weeks starting from C1D22 until participant meets study treatment discontinuation criteria. Each cycle was approximately 42 days.
DRUG	placebo	Participants received an IV infusion (as a minimum of 2-hour infusion) of placebo matched to zolbetuximab on C1D1 followed by subsequent doses every 3 weeks starting from C1D22 until participant met study treatment discontinuation criteria. Each cycle was approximately 42 days.
DRUG	oxaliplatin	Participants received up to 12 treatments of oxaliplatin administered 85 mg/m\^2 IV infusion over 2 hours) on Days 1, 15 and 29 of each cycle.. A maximum of 12 doses of oxaliplatin was permitted. Each cycle was approximately 42 days.
DRUG	folinic acid	Participants received up to 12 treatments of folinic acid administered 400 mg/m\^2 IV infusion over 2 hours 4 or more cycles on Days 1, 15 and 29 of each cycle. participants could continue to receive folinic acid on Days 1, 15 and 29 of each cycle at the investigator's discretion or until the participant met the study treatment discontinuation criteria. Each cycle was approximately 42 days.
DRUG	fluorouracil	Participants received up to 12 treatments of 5-fluorouracil over 4 or more cycles administered by IV bolus 400 mg/m\^2 over 5 to 15 minutes followed by 2400mg/m\^2 over 46-48 hours continuous IV infusion every 2 weeks for 4 cycles. Participants could continue to receive 5-fluorouracil on Days 1, 15 and 29 of each cycle at the investigator's discretion or until the participant met the study treatment discontinuation criteria. Each cycle was approximately 42 days.

Timeline

Start date: 2018-06-21
Primary completion: 2022-09-09
Completion: 2026-09-30
First posted: 2018-04-20
Last updated: 2026-02-13
Results posted: 2025-02-26

Locations

220 sites across 20 countries: United States, Australia, Belgium, Brazil, Canada, Chile, China, Colombia, France, Germany, Israel, Italy, Japan, Mexico, Peru, Poland, South Korea, Spain, Taiwan, United Kingdom

Regulatory

FDA-regulated drug study

Source: ClinicalTrials.gov record NCT03504397. Inclusion in this directory is not an endorsement.