Immunotherapy + Chemotherapy for Esophageal Cancer

(CheckMate 648 Trial)

No longer recruiting at 429 trial locations
Age: 18+
Sex: Any
Trial Phase: Phase 3
Sponsor: Bristol-Myers Squibb
No Placebo GroupAll 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 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?

This trial tests new treatment combinations to determine if they help people with esophageal cancer live longer or prevent cancer growth. It compares three groups: one receiving two immunotherapies (nivolumab and ipilimumab), another receiving the same immunotherapies plus chemotherapy (fluorouracil and cisplatin), and a group receiving traditional chemotherapy. People with esophageal cancer that cannot be surgically removed or treated with radiation, and who can still perform light activities, might be suitable for this study. As a Phase 3 trial, it represents the final step before FDA approval, offering participants access to potentially effective treatments.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

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

Research has shown that the combination of nivolumab and ipilimumab is generally well-tolerated. One study found that serious side effects occurred in 30% of patients who received these drugs with chemotherapy. However, this combination reduced the risk of disease progression or death by 38% compared to using nivolumab alone.

Studies have demonstrated that the combination of nivolumab with cisplatin and fluorouracil helps patients with advanced esophageal cancer live longer. This combination has received FDA approval for similar conditions, indicating its safety.

While both treatments carry risks of side effects, extensive studies have shown promising results in terms of safety and effectiveness.12345

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments because they combine traditional chemotherapy with cutting-edge immunotherapy. Unlike standard treatments for esophageal cancer that typically rely on chemotherapy alone, like Cisplatin and Fluorouracil, the addition of immunotherapy drugs such as Nivolumab and Ipilimumab offers a new approach by harnessing the immune system to fight the cancer. This immunotherapy works by blocking proteins that prevent the immune system from attacking cancer cells, potentially leading to more effective and targeted treatment. This innovative approach could improve outcomes for patients by enhancing the body's natural defenses against cancer.

What evidence suggests that this trial's treatments could be effective for esophageal cancer?

Research has shown that using nivolumab and ipilimumab together may help treat esophageal cancer. In clinical trials, patients receiving this combination had a 38% lower risk of disease progression or death compared to those taking nivolumab alone. Another study found that this combination also provided better overall survival benefits than chemotherapy alone. One arm of this trial will study the combination of nivolumab and ipilimumab.

Another arm will study the combination of nivolumab with the chemotherapy drugs cisplatin and fluorouracil. Studies have shown this combination offers a significant survival advantage for patients with advanced esophageal cancer, with higher response rates than other treatments. Both treatment options are under investigation in this trial for their potential to improve outcomes in esophageal cancer.35678

Who Is on the Research Team?

BS

Bristol-Myers Squibb

Principal Investigator

Bristol-Myers Squibb

Are You a Good Fit for This Trial?

This trial is for adults with esophageal cancer that's inoperable, recurrent, or metastatic. Participants must be able to perform light activities and provide a tumor tissue sample. It excludes those with symptomatic brain/spinal tumors, serious medical conditions, active infections, HIV/AIDS, hepatitis B/C infection, or autoimmune diseases.

Inclusion Criteria

I can walk and do light activities like housework or office work.
My cancer is a type of esophageal cancer called squamous cell or adenosquamous carcinoma.
My esophageal cancer is advanced, cannot be surgically removed, or treated with the intent to cure.
See 1 more

Exclusion Criteria

I have tested positive for hepatitis B or C.
I have cancer in my brain or spinal cord that shows symptoms or needs treatment.
I have tested positive for HIV/AIDS.
See 2 more

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either nivolumab plus ipilimumab, nivolumab combined with fluorouracil plus cisplatin, or fluorouracil plus cisplatin

9 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

16 months

What Are the Treatments Tested in This Trial?

Interventions

  • Cisplatin
  • Fluorouracil
  • Ipilimumab
  • Nivolumab
Trial Overview The study compares the effectiveness of Nivolumab plus Ipilimumab or combined with Fluorouracil and Cisplatin against just Fluorouracil plus Cisplatin in extending life without disease progression in esophageal cancer patients.
How Is the Trial Designed?
3Treatment groups
Experimental Treatment
Active Control
Group I: Nivolumab + IpilimumabExperimental Treatment2 Interventions
Group II: Nivolumab + Cisplatin + FluorouacilExperimental Treatment3 Interventions
Group III: Cisplatin + FluorouracilActive Control2 Interventions

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

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Approved in European Union as Platinol for:
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Approved in United States as Platinol for:
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Approved in Canada as Platinol for:
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Approved in Japan as Platinol for:

Find a Clinic Near You

Who Is Running the Clinical Trial?

Bristol-Myers Squibb

Lead Sponsor

Trials
2,731
Recruited
4,127,000+
Headquarters
New York City, USA
Known For
Oncology & Cardiovascular
Top Products
Eliquis, Opdivo, Revlimid, Orencia
Christopher Boerner profile image

Christopher Boerner

Bristol-Myers Squibb

Chief Executive Officer since 2023

PhD in Business Administration from the Haas School of Business, University of California, Berkeley; BA in Economics and History from Washington University in St. Louis

Deepak L. Bhatt profile image

Deepak L. Bhatt

Bristol-Myers Squibb

Chief Medical Officer since 2024

MD from Yale University; MSc in Clinical Epidemiology from the University of Pennsylvania

Ono Pharmaceutical Co. Ltd

Industry Sponsor

Trials
182
Recruited
97,100+
Shinji Takai profile image

Shinji Takai

Ono Pharmaceutical Co. Ltd

Chief Medical Officer since 2023

MD from an unspecified institution

Gyo Sagara profile image

Gyo Sagara

Ono Pharmaceutical Co. Ltd

Chief Executive Officer since 2024

PhD in Pharmaceutical Sciences from Kyoto University

Citations

Nivolumab Combination Therapy in Advanced Esophageal ...The monoclonal antibody nivolumab has shown an overall survival benefit over chemotherapy in previously treated patients with advanced esophageal squamous-cell ...
Does nivolumab combined with fluorouracil-based ...Does nivolumab combined with fluorouracil-based chemotherapy produce higher objective response rate than other immunochemotherapy regimes in metastatic ...
OPDIVO® (nivolumab) + Chemo Checkmate 649 ...View efficacy information from the Checkmate 649 & Checkmate 648 clinical trials for OPDIVO® (nivolumab) + chemotherapy (fluoropyrimidine- and ...
CheckMate 648: A randomized phase 3 study of nivolumab ...This randomized phase 3 study will evaluate the efficacy and safety of NIVO + IPI or NIVO + fluorouracil (5-FU)/cisplatin (Cis) vs 5-FU/Cis as first-line ...
Immune Checkpoint Inhibitor, Nivolumab, Combined with ...The prognosis of esophageal cancer is poor, with a 5-year survival rate of 19% in the United States, 12.4% in Europe, and 20.9% in China [15,16, ...
Selected safety profile - OpdivoView safety data for Checkmate 649 & Checkmate 648 OPDIVO® (nivolumab) + chemotherapy (fluoropyrimidine- and platinum-containing) in mUGI and ESCC cancers.
Safety and short-term efficacy of adjuvant nivolumab after ...Background: Efficacy and safety of adjuvant nivolumab has been demonstrated in patients with locally advanced esophageal cancer who received ...
FDA approves nivolumab in combination with ...CHECKMATE-649 demonstrated a statistically significant improvement in PFS and OS for patients with PD-L1 CPS ≥5. Median OS was 14.4 months (95% ...
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