565 Participants Needed

Zolbetuximab + Chemotherapy for Gastric Cancer

(Spotlight Trial)

Recruiting at 226 trial locations
AP
Overseen ByAstellas Pharma Global Development
Age: 18+
Sex: Any
Trial Phase: Phase 3
Sponsor: Astellas Pharma Global Development, Inc.
Pivotal Trial (Near Approval)This treatment is in the last trial phase before FDA approval
Prior Safety DataThis treatment has passed at least one previous human trial

What You Need to Know Before You Apply

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 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.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you cannot participate if you need medicines that suppress your immune system or if you have certain medical conditions. It's best to discuss your specific medications with the study doctor.

What makes the drug Zolbetuximab combined with chemotherapy unique for treating gastric cancer?

Zolbetuximab is unique because it targets a specific protein called Claudin 18.2, which is found in certain gastric cancers, and works by helping the immune system attack cancer cells. This makes it different from other treatments that do not specifically target this protein.12345

What data supports the effectiveness of the drug Zolbetuximab combined with chemotherapy for gastric cancer?

Research shows that combining oxaliplatin with 5-fluorouracil (5-FU) and folinic acid is effective for advanced gastric cancer, and similar combinations have improved survival in patients with certain types of gastric cancer. This suggests that the combination of Zolbetuximab with these chemotherapy drugs may also be effective.678910

Who Is on the Research Team?

GM

Global Medical Lead

Principal Investigator

Astellas Pharma Global Development, Inc.

Are You a Good Fit for This Trial?

Adults with advanced unresectable or metastatic gastric/GEJ cancer that's HER2-negative and expresses Claudin 18.2 proteins can join this trial. They must have an ECOG performance status of 0-1, indicating they are fully active or restricted in physically strenuous activity but ambulatory. Participants should not be pregnant, breastfeeding, or planning to donate eggs/sperm; contraception is required. Those who've had certain treatments for these cancers within specific timeframes before the study starts cannot participate.

Inclusion Criteria

I agree not to breastfeed during and for 6 months after the study.
I will not donate eggs during and up to 9 months after my last oxaliplatin dose, and 6 months after other study drugs.
Subject must meet laboratory test criteria within 14 days prior to randomization
See 11 more

Exclusion Criteria

I have tested positive for HIV or active hepatitis B or C.
I have been treated for an autoimmune disease in the last 3 months.
I have had chemotherapy for advanced stomach or GEJ cancer that cannot be surgically removed.
See 18 more

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 mFOLFOX6 chemotherapy in 6-week cycles

24 weeks
4 infusions per cycle, clinic visits on Days 1, 15, and 29

Follow-up

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

51 months
Clinic visits 1 month after treatment, then scans every 9 or 12 weeks, and telephone health checks every 3 months

Extension

Participants may continue receiving folinic acid and fluorouracil chemotherapy after mFOLFOX6 treatment

Until disease progression or intolerance

What Are the Treatments Tested in This Trial?

Interventions

  • Fluorouracil
  • Folinic Acid
  • Oxaliplatin
  • Placebo
  • Zolbetuximab
Trial Overview The trial tests zolbetuximab (IMAB362), which targets Claudin 18.2 on cancer cells, combined with mFOLFOX6 chemotherapy versus a placebo plus mFOLFOX6 in patients with specific gastric cancers. The goal is to see if zolbetuximab helps extend life by preventing cancer progression.
How Is the Trial Designed?
2Treatment groups
Experimental Treatment
Placebo Group
Group I: mFOLFOX6 + ZolbetuximabExperimental Treatment4 Interventions
Group II: Placebo plus mFOLFOX6Placebo Group4 Interventions

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

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Approved in United States as 5-Fluorouracil for:
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Approved in European Union as 5-Fluorouracil for:
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Approved in Canada as 5-Fluorouracil for:

Find a Clinic Near You

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 profile image

Naoki Okamura

Astellas Pharma Global Development, Inc.

Chief Executive Officer

Not available

Published Research Related to This Trial

In a study of 115 patients with advanced gastric cancer, the combination of irinotecan, 5-fluorouracil (5-FU), and folinic acid (FA) showed a higher overall response rate of 42.4% and a median survival time of 10.7 months compared to 32.1% and 6.9 months for the irinotecan/cisplatin combination.
The irinotecan/5-FU/FA regimen had a better safety profile, with significantly lower rates of severe neutropenia (27% vs. 65.7%) compared to irinotecan/cisplatin, making it the preferred choice for further investigation in a phase III trial.
Irinotecan in combination with 5-fluorouracil and folinic acid or with cisplatin in patients with advanced gastric or esophageal-gastric junction adenocarcinoma: results of a randomized phase II study.Pozzo, C., Barone, C., Szanto, J., et al.[2020]
In a study of 263 gastric cancer samples from Japanese patients, 87% of primary tumors and 80% of lymph node metastases expressed the biomarker CLDN18.2, indicating a high prevalence that supports the use of zolbetuximab as a treatment option.
Moderate-to-strong expression of CLDN18.2 was found in 52% of primary tumors and 45% of lymph node metastases, particularly in high-grade tumors and those of the diffuse histological subtype, suggesting that zolbetuximab could be particularly effective in these cases.
Comparison of Claudin 18.2 expression in primary tumors and lymph node metastases in Japanese patients with gastric adenocarcinoma.Rohde, C., Yamaguchi, R., Mukhina, S., et al.[2022]

Citations

Irinotecan in combination with 5-fluorouracil and folinic acid or with cisplatin in patients with advanced gastric or esophageal-gastric junction adenocarcinoma: results of a randomized phase II study. [2020]
Oxaliplatin combined with continuous infusion of 5-fluorouracil as first-line chemotherapy in patients with metastatic or recurrent gastric adenocarcinoma. [2018]
Phase II study of oxaliplatin, fluorouracil, and folinic acid in locally advanced or metastatic gastric cancer patients. [2022]
Efficacy and safety of trastuzumab in combination with oxaliplatin and fluorouracil-based chemotherapy for patients with HER2-positive metastatic gastric and gastro-oesophageal junction adenocarcinoma patients: a retrospective study. [2020]
Adjuvant treatment of high-risk, radically resected gastric cancer patients with 5-fluorouracil, leucovorin, cisplatin, and epidoxorubicin in a randomized controlled trial. [2013]
Comparison of Claudin 18.2 expression in primary tumors and lymph node metastases in Japanese patients with gastric adenocarcinoma. [2022]
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]
Claudin18.2 expression and clinicopathological features in cytology effusion specimens from gastric adenocarcinoma: A comparative study with tissue specimens. [2023]
ILUSTRO: Phase II Multicohort Trial of Zolbetuximab in Patients with Advanced or Metastatic Claudin 18.2-Positive Gastric or Gastroesophageal Junction Adenocarcinoma. [2023]
Phase 1 trial of zolbetuximab in Japanese patients with CLDN18.2+ gastric or gastroesophageal junction adenocarcinoma. [2023]
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