Zolbetuximab + Chemotherapy for Gastric Cancer

(Spotlight Trial)

Not currently recruiting at 274 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, Autoimmune, 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: 5

Duration: 24 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called zolbetuximab combined with chemotherapy for individuals with advanced stomach or gastroesophageal junction (GEJ) cancer. Zolbetuximab helps the immune system fight cancer by targeting a specific protein found in these tumors. The trial aims to determine if this combination can slow or prevent cancer progression compared to standard chemotherapy alone. Individuals with advanced stomach or GEJ cancer, whose tumors have a specific protein and who have not yet received chemotherapy for this cancer, might be suitable for this trial. Participants will receive either zolbetuximab with chemotherapy or a placebo with chemotherapy, and neither they nor the doctors will know which group they are in. As a Phase 3 trial, this study represents the final step before potential FDA approval, offering participants a chance to contribute to a treatment that could soon become widely available.

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.

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 individuals with stomach cancer or gastroesophageal junction (GEJ) cancer. In studies, patients receiving this treatment achieved better outcomes compared to those who received a placebo with chemotherapy. This treatment targets a protein called Claudin 18.2, commonly found in these cancers, and aids the immune system in attacking the tumor.

Safety information indicates that zolbetuximab may cause side effects such as nausea, vomiting, and tiredness, which are similar to those seen with many cancer treatments. Importantly, some countries have approved zolbetuximab with chemotherapy for treating gastric and GEJ cancer, indicating it has passed safety checks there. This approval supports its use as a treatment option, but patients should always consult their doctor about potential risks and benefits. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for gastric cancer?

Researchers are excited about zolbetuximab combined with chemotherapy for treating gastric cancer because it introduces a novel approach by targeting a specific protein called Claudin 18.2. Unlike standard treatments, such as mFOLFOX6, which focus on killing rapidly dividing cancer cells, zolbetuximab specifically binds to this protein found on the surface of cancer cells, potentially enhancing the effectiveness of the chemotherapy. This targeted action could lead to more precise treatment, reducing damage to healthy cells and possibly improving outcomes for patients.

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

Research has shown that zolbetuximab, one of the treatments in this trial, helps people with advanced stomach cancer or gastroesophageal junction (GEJ) cancer live longer without their cancer worsening when used with chemotherapy. In this trial, participants will receive either zolbetuximab with chemotherapy or a placebo with chemotherapy. Studies have found that zolbetuximab combined with chemotherapy results in longer periods without cancer progression and longer overall survival compared to a placebo with chemotherapy. Zolbetuximab targets a protein called Claudin 18.2 on cancer cells, aiding the immune system in attacking the cancer. This treatment has already received approval in some countries, demonstrating its effectiveness in treating gastric and GEJ cancers. ^{1 2 5 6 7}

Who Is on the Research Team?

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 has predicted life expectancy ≥ 12 weeks

Exclusion Criteria

I have been treated for an autoimmune disease in the last 3 months.

I have tested positive for HIV or active hepatitis B or C.

I have had chemotherapy for advanced stomach or GEJ cancer that cannot be surgically removed.

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?

Group I: mFOLFOX6 + Zolbetuximab Experimental Treatment 4 Interventions

Participants received intravenous (IV) infusion (minimum 2-hour) of zolbetuximab at a loading dose of 800 milligrams per square meter (mg/m\^2) on cycle1 day1(C1D1) followed by 600 mg/m\^2 every 3 weeks starting from C1D22 until study treatment discontinuation criteria were met. Participants also received upto 12 treatments of mFOLFOX6 (or components if some were discontinued due to toxicity) over 4/more cycles. mFOLFOX6 was administered on Days 1, 15 \& 29 of each cycle (5-FU:400mg/m\^2 IV bolus over 5-15 minutes followed by 2400mg/m\^2 over 46-48 hours continuous IV infusion every 2 weeks for 4 cycles. Folinic acid: 400mg/m\^2 IV infusion over 2 hours; oxaliplatin: 85mg/m\^2 IV infusion over 2 hours) A maximum of 12 doses of oxaliplatin was permitted. After mFOLFOX6 treatments, participants continued to receive 5-FU \& Folinic acid on Days 1, 15 \& 29 of each cycle at the investigator discretion or until study treatment discontinuation criteria were met. Each cycle was approximately 42 days.

Group II: Placebo plus mFOLFOX6 Placebo Group 4 Interventions

Participants received an IV infusion (minimum 2-hour infusion) of placebo matched to zolbetuximab on C1D1, followed by subsequent doses every 3 weeks starting from C1D22 until study treatment discontinuation criteria were met. Participants also received up to 12 treatments of mFOLFOX6 (or components if some were discontinued due to toxicity) over 4 or more cycles. mFOLFOX6 was administered on Days 1, 15, and 29 of each cycle (5-fluorouracil: 400 mg/m\^2 IV bolus over 5-15 minutes followed by 2400mg/m\^2 over 46-48 hours continuous IV infusion every 2 weeks for 4 cycles. Folinic acid: 400 mg/m\^2 IV infusion over 2 hours; oxaliplatin: 85 mg/m\^2 IV infusion over 2 hours). A maximum of 12 doses of oxaliplatin was permitted. After mFOLFOX6 treatments, participants could continue to receive 5-FU and folinic acid on Days 1, 15, and 29 of each cycle at the investigator's discretion or until study treatment discontinuation criteria were met. Each cycle was approximately 42 days.

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

Approved in United States as 5-Fluorouracil for:

• Colorectal cancer
• Breast cancer
• Stomach cancer
• Pancreatic cancer
• Skin cancer

Approved in European Union as 5-Fluorouracil for:

• Colorectal cancer
• Breast cancer
• Stomach cancer
• Pancreatic cancer

Approved in Canada as 5-Fluorouracil for:

• Colorectal cancer
• Breast cancer
• Stomach cancer
• Pancreatic 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

Published Research Related to This Trial

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.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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]

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.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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]

Citations

1. 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.

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39699854/

Efficacy and Safety of Zolbetuximab in Gastric Cancer In clinical trials, zolbetuximab with chemotherapy improved progression-free survival (PFS) and overall survival (OS). The FAST trial showed ...

3. 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- ...

4. 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.

5. 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 ... The major efficacy outcome measure in both trials was progression ...

6. 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 ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6771222/

A multicentre, phase IIa study of zolbetuximab as a single ... Considering this, the safety of repeated infusions of zolbetuximab for gastric and GEJ cancers was established in this study. The small number of ...