Zolbetuximab + Chemotherapy for Gastric or Gastroesophageal Junction Cancer

(GLOW Trial)

Not currently recruiting at 216 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment, zolbetuximab, combined with chemotherapy, for individuals with advanced stomach cancer or cancer where the food pipe meets the stomach (GEJ cancer). Zolbetuximab helps the immune system attack cancer by targeting a specific protein in the tumor called Claudin 18.2. Participants will receive either zolbetuximab with chemotherapy or a placebo (a look-alike with no active medicine) with chemotherapy. This trial is for adults with advanced stomach or GEJ cancer whose cancer cannot be removed by surgery and have a specific protein in their tumor. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking cancer treatment.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that zolbetuximab, when combined with chemotherapy, is generally well-tolerated by patients with stomach or gastroesophageal junction cancer. One study found that patients receiving this combination lived longer without their cancer worsening and had a longer overall survival compared to those who received a placebo with chemotherapy. This indicates that the treatment is both effective and manageable for patients.

Furthermore, the FDA has approved zolbetuximab for treating stomach or gastroesophageal junction adenocarcinoma when used with chemotherapy. This approval confirms it has been tested and found safe and effective for these cancer types.

While all treatments can have side effects, existing studies and FDA approval suggest that zolbetuximab with chemotherapy offers a promising option with a manageable safety profile for people with this type of cancer. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for stomach or GEJ cancer?

Researchers are excited about zolbetuximab for gastric or gastroesophageal junction cancer because it offers a new approach by targeting a specific protein called Claudin 18.2, which is often found in these types of cancer cells. Unlike the standard chemotherapy options like capecitabine and oxaliplatin, zolbetuximab aims to block this protein, potentially preventing cancer growth more effectively. This targeted action might enhance the effectiveness of existing treatments and improve outcomes for patients with this challenging condition.

What evidence suggests that zolbetuximab combined with chemotherapy could be an effective treatment for gastric or GEJ cancer?

This trial will compare the combination of zolbetuximab with chemotherapy to a placebo with chemotherapy for individuals with stomach or gastroesophageal junction (GEJ) cancer. Studies have shown that combining zolbetuximab with chemotherapy extends the time patients live without their cancer worsening. Research indicates that this combination improves progression-free survival, meaning more time without cancer growth, and overall survival compared to chemotherapy alone. Zolbetuximab targets a protein called Claudin 18.2, found in many stomach and GEJ cancers, aiding the immune system in attacking cancer cells. Patients whose tumors contain this protein have benefited from this treatment. This treatment has received approval in some countries, demonstrating its effectiveness in treating these cancer types. ^{2 5 6 7 8}

Who Is on the Research Team?

Medical Director

Principal Investigator

Astellas Pharma Global Development

Are You a Good Fit for This Trial?

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.

I am severely allergic to zolbetuximab or similar drugs.

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

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Citations

1.

nejm.org

nejm.org/doi/full/10.1056/NEJMc2409512

Zolbetuximab in Gastric or Gastroesophageal Junction ...

Zolbetuximab plus chemotherapy resulted in longer progression-free survival and overall survival than placebo plus chemotherapy among patients with HER2- ...

2.

clinicaltrials.gov

clinicaltrials.gov/study/NCT03504397

NCT03504397 | A Study to Compare Zolbetuximab ...

This study will give more information about how well zolbetuximab works when given with chemotherapy in adults with advanced stomach cancer or GEJ cancer.

3.

vyloy.com

vyloy.com/clinical-trial-results

VYLOY® (zolbetuximab-clzb) Clinical Trial Results

VYLOY (zolbetuximab-clzb) was studied in combination with chemotherapy in 2 clinical trials of patients with advanced stomach or GEJ cancer.

4.

fda.gov

fda.gov/drugs/resources-information-approved-drugs/fda-approves-zolbetuximab-clzb-chemotherapy-gastric-or-gastroesophageal-junction-adenocarcinoma

FDA approves zolbetuximab-clzb with chemotherapy

FDA approves zolbetuximab-clzb with chemotherapy for gastric or gastroesophageal junction adenocarcinoma ... The major efficacy outcome ...

5.

nature.com

nature.com/articles/s41591-023-02465-7

Zolbetuximab plus CAPOX in CLDN18.2-positive gastric or ...

Subsequent anti-cancer therapies were administered to 118 of 254 (46.5%) patients in the zolbetuximab arm versus 140 of 253 (55.3%) patients in ...

6.

clinicaltrials.gov

clinicaltrials.gov/study/NCT06902545

A Study to Observe the Safety of VYLOY (Zolbetuximab) in ...

This study is for people in South Korea who have cancer in or around the stomach (gastric cancer) or cancer where the food pipe (esophagus) joins the ...

7.

clinicaltrials.astellas.com

clinicaltrials.astellas.com/study/8951-CL-0103

A study of zolbetuximab (IMAB362) in adults with gastric ...

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 ...

8.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC10768589/

Zolbetuximab for Claudin18.2-positive gastric or ...

Zolbetuximab combined with chemotherapy demonstrated a survival benefit in patients with CLDN18.2-positive and HER-2-negative gastric or gastroesophageal ...