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

Conditions

• Locally Advanced Unresectable Gastric Adenocarcinoma or Cancer
• Locally Advanced Unresectable Gastroesophageal Junction (GEJ) Adenocarcinoma or Cancer
• Metastatic Gastric Adenocarcinoma or Cancer
• Metastatic Gastroesophageal Junction (GEJ) Adenocarcinoma

Eligibility Criteria

Sex

ALL

Age

18 Years - N/A

Healthy Volunteers

Not accepted

Interventions

• zolbetuximab — DRUG
  Participants will receive an IV infusion of zolbetuximab on Cycle 1 Day 1 (C1D1) followed by subsequent IV infusion every 2 weeks or every 3 weeks.
• Pembrolizumab — DRUG
  Participants will receive an IV infusion of pembrolizumab every 3 weeks or every 6 weeks.
• Capecitabine — DRUG
  Participants receiving CAPOX regimen of chemotherapy will receive capecitabine Tablet twice daily orally on days 1 through 14 and days 22 through 35 of each cycle.
• Oxaliplatin — DRUG
  Participants receiving CAPOX or mFOLFOX6 regimen of chemotherapy will receive an IV infusion of oxaliplatin once every 2 or 3 weeks.
• Folinic acid (leucovorin or local equivalent) — DRUG
  Participants receiving mFOLFOX6 regimen of chemotherapy will receive an IV infusion of Folinic acid (leucovorin or local equivalent) once every 2 weeks.
• 5-fluorouracil (5-FU) — DRUG
  Participants receiving mFOLFOX6 regimen of chemotherapy will receive an IV infusion, or IV bolus of 5-FU once every 2 weeks.
• Placebo — DRUG
  Participants will receive an IV infusion of placebo (0.9% of sodium chloride) on C1D1 followed by subsequent IV infusion every 2 weeks or every 3 weeks.

Study Details

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. Zolbetuximab with chemotherapy may be used to treat stomach and GEJ cancer when the cancer cells do not have a protein called HER2 (human epidermal growth factor receptor 2) on their surface (HER2-negative) but do have a protein called Claudin 18.2 (Claudin 18.2-positive). 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. Certain stomach and GEJ cancers may be treated with immunotherapy, which helps the body's immune system fight cancer. This study will give more information about how well zolbetuximab works when given with an immunotherapy medicine called pembrolizumab and chemotherapy. In this study, adults with stomach cancer or GEJ cancer will either be given zolbetuximab with pembrolizumab and chemotherapy or a placebo with pembrolizumab and chemotherapy. A placebo looks like zolbetuximab but doesn't have any medicine in it. The main aim of the study is to check how long people with stomach cancer and GEJ cancer live after treatment with zolbetuximab with pembrolizumab and chemotherapy compared to placebo with pembrolizumab and chemotherapy. Adults with locally advanced unresectable or metastatic 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 (biopsy) of their cancer will have the Claudin 18.2 protein, PD-L1 protein, and be HER2-negative. They may have been previously treated with certain standard therapies. People can also take part if they need to take medicines like steroids to suppress their immune system. They cannot take part if they 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 pembrolizumab and chemotherapy, or placebo with pembrolizumab and chemotherapy. People who take part will receive just 1 of the study treatments by chance. 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 6-week (42-day) cycles. The study treatment is mainly given to people slowly through a tube into a vein. This is called an infusion. People will receive study treatment as follows: Zolbetuximab or placebo: 1 infusion every 2 or 3 weeks (2 or 3 infusions in a cycle) together with: Chemotherapy (1 of the following types of chemotherapy): 1. CAPOX (capecitabine and oxaliplatin): 1 infusion of oxaliplatin every 3 weeks (2 infusions in a cycle). People will also take 1 tablet of capecitabine twice a day for 2 weeks (14 days) at the start of each cycle (Day 1) and again in the middle of each cycle (Day 22). After 8 study treatments people will receive capecitabine only. 2. Modified FOLFOX6 or mFOLFOX6 (5-fluorouracil, folinic acid and oxaliplatin): 1 infusion every 2 weeks (3 infusions in a cycle). After 12 study treatments people will receive folinic acid and fluorouracil only, instead of mFOLFOX6. Pembrolizumab: 1 infusion every 3 or 6 weeks (1 or 2 infusions in a cycle). People can be in the study and will receive study treatment until their cancer worsens, they cannot tolerate the study treatment, or they need to start another cancer treatment. People may receive pembrolizumab for up to 2 years. People will visit the clinic on certain days to receive their study treatment and have health checks. The study doctors will check if people had any medical problems from taking zolbetuximab or the other study treatments. 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 if they stop treatment because their cancer has worsened. People will visit the clinic after they stop their study treatment. People will be asked about any medical problems and will have a health check. People will continue to have scans every 9 or 12 weeks to check for any changes in their cancer. They 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.

Key Dates

Start date

May 22, 2025

Status verified

Jun 2026

Primary completion

Sep 30, 2028

Completion

Sep 30, 2028

Study Design

Enrollment

500 participants (estimated)

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Arms

• Experimental: Arm A: zolbetuximab in combination with pembrolizumab and chemotherapy
  Participants will receive zolbetuximab as an intravenous (via a vein) infusion at 800 mg/m2 loading dose at C1D1 followed by subsequent doses of 400 mg/m2 every 2 weeks; or 800 mg/m2 loading dose at C1D1 followed by subsequent doses of 600 mg/m2 every 3 weeks, followed by an intravenous infusion of pembrolizumab at a dose of 200 mg every 3 weeks or 400 mg every 6 weeks. Participants will then receive chemotherapy over 4 or more cycles of either up to 8 CAPOX treatments (oxaliplatin: 130 mg/m2 once every 3 weeks, capecitabine: 1000 mg/m2 twice daily on days 1 through 14 and days 22 through 35 of each cycle), or, up to 12 mFOLFOX6 treatments (oxaliplatin: 85 mg/m2, Folinic acid (leucovorin/local equivalent): 400 mg/m2, 5-FU bolus: 400 mg/m2, 5-FU infusion: 2400 mg/m2) once every 2 weeks (or components of mFOLFOX6 if some components are discontinued due to toxicity). The choice of chemotherapy for each participant is based on investigator's judgment. Each cycle is approximately 42 days.
• Active Comparator: Arm B: Placebo in combination with pembrolizumab and chemotherapy
  Participants will receive matching placebo as an intravenous (via a vein) infusion followed by an intravenous infusion of pembrolizumab at a dose of 200 mg every 3 weeks or 400 mg every 6 weeks. Participants will then receive chemotherapy over 4 or more cycles of either up to 8 CAPOX treatments (oxaliplatin: 130 mg/m2 once every 3 weeks, capecitabine: 1000 mg/m2 twice daily on days 1 through 14 and days 22 through 35 of each cycle), or, up to 12 mFOLFOX6 treatments (oxaliplatin: 85 mg/m2, Folinic acid (leucovorin/local equivalent): 400 mg/m2, 5-FU bolus: 400 mg/m2, 5-FU infusion: 2400 mg/m2) once every 2 weeks (or components of mFOLFOX6 if some components are discontinued due to toxicity). The choice of chemotherapy for each participant is based on investigator's judgment. Each cycle is approximately 42 days.

Primary Outcome Measure

Overall Survival (OS) [ Time Frame: Up to 72 months ]

Central Contacts

• Astellas Pharma Global Development Inc.
  800-888-7704
  [email protected]

Locations (36)

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