Zolbetuximab + Pembrolizumab for Stomach Cancer

(LUCERNA Trial)

Recruiting at 127 trial locations

Overseen By Astellas Pharma Global Development Inc.

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Astellas Pharma Global Development, Inc.

Must be taking: mFOLFOX6, CAPOX, Pembrolizumab

Must not be taking: Immunosuppressants, Corticosteroids

Disqualifiers: HIV, Hepatitis B, CNS metastases, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

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: 11

Duration: Up to 72 months

500 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new combination of treatments for stomach cancer and cancer where the esophagus meets the stomach (GEJ cancer). Researchers aim to determine if adding zolbetuximab, which aids the immune system in attacking tumors, to the standard treatment of pembrolizumab (an immunotherapy drug) and chemotherapy can extend patients' lives. Participants will receive either the new treatment combination or a placebo (a harmless, inactive substance) with the same standard treatment. Individuals with advanced stomach or GEJ cancer that cannot be surgically removed, who have HER2-negative and Claudin 18.2-positive tumors, and who do not have certain health issues, might be suitable candidates for this study. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

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 to suppress your immune system or if you have certain medical conditions. It's best to discuss your specific medications with the study doctors.

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

Research has shown that zolbetuximab, when combined with pembrolizumab, has generally been well-tolerated in past studies. In earlier research, patients experienced some side effects, but these were mostly manageable. Common side effects included nausea, tiredness, and low blood cell counts, while serious side effects were less common.

Pembrolizumab is already approved for certain cancers and is known to be effective. However, it can cause side effects like fatigue, rash, and diarrhea. Most people handle these well, but more serious effects can occur, so careful monitoring is important.

Since this trial is in a later phase, a substantial amount of safety information already exists. Earlier trials likely demonstrated the treatment to be safe enough to continue. Participants will be closely monitored during the trial to manage any side effects that may occur. ^{1 2 3 4 5}

Why are researchers excited about this study treatment for stomach cancer?

Researchers are excited about zolbetuximab for stomach cancer because it offers a novel way to target cancer cells. Unlike most treatments that focus on traditional chemotherapy, zolbetuximab is an antibody that specifically targets a protein called CLDN18.2, which is often found on the surface of stomach cancer cells. This targeted approach could potentially improve treatment effectiveness by honing in on cancer cells more precisely, reducing damage to healthy cells. Additionally, combining zolbetuximab with pembrolizumab—a drug that helps the immune system recognize and fight cancer cells—could enhance the overall immune response against the tumor.

What evidence suggests that zolbetuximab with pembrolizumab and chemotherapy could be an effective treatment for stomach and GEJ cancer?

Research has shown that zolbetuximab, which participants in this trial may receive, attaches to a protein called Claudin 18.2, found in some stomach cancers. This protein aids the immune system in attacking the tumor. Studies have demonstrated that combining the drug pembrolizumab with chemotherapy improves response rates for patients with HER2-negative stomach cancer. Early findings suggest that adding zolbetuximab to this combination, as tested in Arm A of this trial, could further enhance these benefits. Meanwhile, Arm B tests a placebo in combination with pembrolizumab and chemotherapy. While the effectiveness of each treatment can vary, this approach targets specific cancer features to potentially improve patient survival. ^{1 3 5 6 7}

Who Is on the Research Team?

Medical Monitor

Principal Investigator

Astellas Pharma Global Development, Inc.

Are You a Good Fit for This Trial?

Adults with advanced stomach or GEJ cancer that can't be removed by surgery or has spread, and who have not been treated with certain therapies may join. They must have tumors without HER2 but with Claudin 18.2 and PD-L1 proteins. Participants need a life expectancy of at least 12 weeks, good physical function (ECOG 0-1), and agree to contraception rules. Those with immune system suppression needs, gut blockages/bleeding, specific cancers in the nervous system, heart conditions, or infections cannot join.

Inclusion Criteria

I am fully active or can carry out light work.

My doctor expects me to live 12 weeks or more.

I am not able to become pregnant.

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 pembrolizumab and chemotherapy in 6-week cycles

Up to 72 months

Infusions every 2-3 weeks, clinic visits for health checks and scans

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 72 months

Scans every 9-12 weeks, telephone health checks every 3 months

What Are the Treatments Tested in This Trial?

Interventions

• Capecitabine
• Pembrolizumab
• Zolbetuximab

Trial Overview The trial is testing zolbetuximab combined with pembrolizumab (an immunotherapy drug) and chemotherapy versus a placebo plus pembrolizumab and chemotherapy for treating stomach and GEJ cancer. It's randomized and double-blind—neither doctors nor participants know who gets which treatment—and involves cycles of infusions over six weeks.

How Is the Trial Designed?

Group I: Arm A: zolbetuximab in combination with pembrolizumab and chemotherapy Experimental Treatment 6 Interventions

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.

Group II: Arm B: Placebo in combination with pembrolizumab and chemotherapy Active Control 6 Interventions

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.

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. clinicaltrials.gov clinicaltrials.gov/study/NCT06901531

NCT06901531 | A Study of Zolbetuximab Together With ... 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 ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11987827/

Treatment Selection for Patients with HER2-Negative ... Both nivolumab and pembrolizumab combined with chemotherapy improved ORR by approximately 10–15% compared to chemotherapy alone; however, no ...

3. ascopubs.org ascopubs.org/doi/10.1200/JCO.2021.39.3_suppl.TPS260

Phase II study of zolbetuximab plus pembrolizumab in ... Background: Five-year survival with advanced G/GEJ is poor, and limited biomarkers exist to inform optimal treatment selection.

4. sciencedirect.com sciencedirect.com/science/article/pii/S095980492500303X

Navigating the clinical challenges of zolbetuximab in ... Anti PD1 agents nivolumab and pembrolizumab, significantly improved survival in combination with chemotherapy in patients with HER2-negative PD- ...

5. academic.oup.com academic.oup.com/oncolo/article/30/7/oyaf185/8174925

New tool in the toolbox: patient selection for zolbetuximab in ... Here, we review data from GLOW and SPOTLIGHT trials and discuss key tumor and patient characteristics and propose a therapeutic algorithm to ...

6. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2025-03502

A Study of Zolbetuximab Together With Pembrolizumab ... 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 ...

7. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK616214/

Clinical Review - Zolbetuximab for Injection (Vyloy) - NCBI - NIH In Canada from 2015 to 2017, the 5-year net survival rate for individuals diagnosed with stomach cancer was 29%, reflecting that diagnosis is often made at ...