Zolbetuximab + Chemotherapy for Gastric or Gastroesophageal Junction Cancer

(GLOW Trial)

Recruiting at 171 trial locations

Overseen By Astellas Pharma Global Development

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Astellas Pharma Global Development, Inc.

Must not be taking: Immunosuppressants, Corticosteroids

Disqualifiers: Chemotherapy, Radiotherapy, Immunosuppressants, Cardiovascular, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 4

Duration: 24 weeks

507 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial does not specify if you must stop taking your current medications. However, you cannot participate if you need to take medicines that suppress your immune system or if you have taken certain treatments with known antitumor activity within 28 days before starting the trial.

What data supports the effectiveness of the drug Zolbetuximab plus chemotherapy for gastric or gastroesophageal junction cancer?

Research shows that Zolbetuximab, when combined with chemotherapy, improves survival rates in patients with certain types of advanced gastric or gastroesophageal junction cancer. Studies like the SPOTLIGHT and FAST trials found that this combination helps patients live longer without the cancer getting worse. ^{1 2 3 4 5}

Is zolbetuximab safe for humans?

Zolbetuximab has been tested in several trials, and no new safety concerns were found. Most side effects were related to the digestive system, and no severe drug-related side effects were observed in a study with Japanese patients. ^{1 2 3 5 6}

What makes the drug Zolbetuximab unique for treating gastric or gastroesophageal junction cancer?

Zolbetuximab is unique because it targets a specific protein called claudin 18.2, which is found on certain cancer cells, and helps the immune system attack these cells. This drug, when combined with chemotherapy, has shown to improve survival rates in patients with claudin 18.2-positive, HER2-negative gastric or gastroesophageal junction cancer, potentially making it a new standard treatment option for these patients. ^{1 2 3 6 7}

What is the purpose of this trial?

Zolbetuximab is being studied in people with cancer in and around the stomach or where the food pipe (esophagus) joins the stomach, called 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 stomach 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 people taking part in those countries will leave this study and receive licensed zolbetuximab. The main aim(s) of the study is(are) to determine the efficacy of zolbetuximab combined with chemotherapy compared to a placebo combined with chemotherapy in treating adults with Claudin 18.2-positive, HER2-negative, locally advanced unresectable or metastatic gastric or GEJ adenocarcinoma. 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 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 one of the 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. The chemotherapy is called CAPOX (capecitabine and oxaliplatin) and will be given as an infusion and also as tablets. People will have 1 infusion of either zolbetuximab or placebo together with oxaliplatin chemotherapy in 3-week (21-day) cycles. People will also take 1 tablet of capecitabine (chemotherapy) twice a day for the first 2 weeks (14 days) of each cycle. People may receive zolbetuximab or placebo until their cancer worsens, they cannot tolerate the treatment, or they need to start another cancer treatment. People will receive CAPOX for up to about 6 months (8 treatment cycles). After the 6 months, people may receive capecitabine chemotherapy only, 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 treatment. The study doctors will check if people had any medical problems from 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 within 7 days after they stop their study treatment. People will be asked about any medical problems and will have a health check. People who start treatment with licensed zolbetuximab will not need to attend the clinic for further visits and will receive standard of care health checks. People who continue study treatment will visit the clinic at 1 and 3 months after they stop their study treatment. They 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 treatment or not.

Research Team

Medical Director

Principal Investigator

Astellas Pharma Global Development

Eligibility Criteria

This trial is for adults with advanced gastric or gastroesophageal junction adenocarcinoma that tests positive for CLDN18.2 and negative for HER2. Participants must have a life expectancy of at least 12 weeks, acceptable organ function, and agree to contraception if applicable. Those who've had recent immunosuppressive therapy, other clinical trials, severe allergies to study drugs, active infections requiring systemic therapy, significant cardiovascular disease or another malignancy needing treatment are excluded.

Inclusion Criteria

My cancer can be measured by scans and was checked within the last 28 days.

My tumor shows high CLDN18.2 expression.

My cancer is advanced and cannot be removed by surgery, confirmed by scans within the last 28 days.

Exclusion Criteria

I have not taken strong immune system suppressing drugs in the last 14 days, except for low-dose steroids or a one-time dose.

You have a known allergy or intolerance to any part of the study treatment.

I am severely allergic to zolbetuximab or similar drugs.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive zolbetuximab or placebo with CAPOX chemotherapy in 3-week cycles for up to 6 months

24 weeks

Clinic visits every 3 weeks

Extended Treatment

Participants may continue to receive capecitabine chemotherapy until disease progression or intolerance

Variable

Follow-up

Participants are monitored for safety and effectiveness after treatment, with scans every 9 or 12 weeks

47 months

Clinic visits at 1 and 3 months post-treatment, then scans every 9-12 weeks

Treatment Details

Interventions

• Capecitabine
• Oxaliplatin
• Placebo
• Zolbetuximab

Trial Overview The trial is testing the effectiveness of zolbetuximab combined with CAPOX (capecitabine and oxaliplatin) versus a placebo plus CAPOX as first-line treatment by measuring how long patients live without their cancer getting worse. It will also assess physical function impacts, safety profiles including side effects, quality of life changes due to the drug regimen and study the body's response to zolbetuximab.

Participant Groups

Group I: Zolbetuximab plus CAPOX Experimental Treatment 3 Interventions

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. Participants also received up to 8 treatments of CAPOX. Oxaliplatin was administered 130 mg/m\^2 IV on day 1 of each cycle over 2 hours for a maximum of 8 treatments; Capecitabine was administered orally at 1000 mg/m\^2 twice daily (bid) on days 1 through 14 of each cycle until the participant met study treatment discontinuation criteria. After a maximum of 8 treatments of oxaliplatin, participants may have continued to receive capecitabine taken twice daily on days 1 through 14 of each cycle at the investigator's discretion until the participant met study treatment discontinuation criteria. Each cycle was approximately 21 days.

Group II: Placebo plus CAPOX Placebo Group 3 Interventions

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 meets study treatment discontinuation criteria. Participants also received up to 8 treatments of CAPOX. Oxaliplatin was administered 130 mg/m\^2 IV on day 1 of each cycle over 2 hours for a maximum of 8 treatments; Capecitabine was administered orally at 1000 mg/m\^2 bid on days 1 through 14 of each cycle until the participant met study treatment discontinuation criteria. After a maximum of 8 treatments of oxaliplatin, participants may have continued to receive capecitabine taken twice daily on days 1 through 14 of each cycle at the investigator's discretion until the participant met study treatment discontinuation criteria. Each cycle was approximately 21 days.

Capecitabine is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Xeloda for:

• Colorectal cancer
• Breast cancer

Approved in United States as Xeloda for:

• Colorectal cancer
• Breast cancer

Approved in Canada as Xeloda for:

• Colorectal cancer
• Breast cancer

Approved in Japan as Xeloda for:

• Colorectal cancer
• Breast cancer

Who Is Running the Clinical Trial?

Astellas Pharma Global Development, Inc.

Lead Sponsor

Trials

204

Recruited

123,000+

Tadaaki Taniguchi

Astellas Pharma Global Development, Inc.

Chief Medical Officer

M.D., Ph.D.

Naoki Okamura

Astellas Pharma Global Development, Inc.

Chief Executive Officer

Not available

References

1. England pubmed.ncbi.nlm.nih.gov

Zolbetuximab plus mFOLFOX6 in patients with CLDN18.2-positive, HER2-negative, untreated, locally advanced unresectable or metastatic gastric or gastro-oesophageal junction adenocarcinoma (SPOTLIGHT): a multicentre, randomised, double-blind, phase 3 trial. [2023]

2. Japan pubmed.ncbi.nlm.nih.gov

Patient-reported outcomes from the phase II FAST trial of zolbetuximab plus EOX compared to EOX alone as first-line treatment of patients with metastatic CLDN18.2+ gastroesophageal adenocarcinoma. [2021]

3. United States pubmed.ncbi.nlm.nih.gov

Zolbetuximab Improves Survival in Gastric Cancer. [2023]

4. England pubmed.ncbi.nlm.nih.gov

CLDN18.2 expression and its impact on prognosis and the immune microenvironment in gastric cancer. [2023]

5. Switzerland pubmed.ncbi.nlm.nih.gov

Efficacy and safety of zolbetuximab for first-line treatment of advanced Claudin 18. 2-positive gastric or gastro-esophageal junction adenocarcinoma: a systematic review and meta-analysis of randomized controlled trials. [2023]

6. England pubmed.ncbi.nlm.nih.gov

Phase 1 trial of zolbetuximab in Japanese patients with CLDN18.2+ gastric or gastroesophageal junction adenocarcinoma. [2023]

7. United States pubmed.ncbi.nlm.nih.gov

ILUSTRO: Phase II Multicohort Trial of Zolbetuximab in Patients with Advanced or Metastatic Claudin 18.2-Positive Gastric or Gastroesophageal Junction Adenocarcinoma. [2023]